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Yirmibes S, Balaban Adim S. A Comparative Study of CD56 and Smooth Muscle Actin Expression in Basal and Squamous Cell Carcinomas. Am J Dermatopathol 2023; 45:816-819. [PMID: 37982465 DOI: 10.1097/dad.0000000000002558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2023]
Abstract
ABSTRACT Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the 2 most common types of nonmelanoma skin tumors. Clinical or histopathological diagnostic challenges are encountered on occasion. CD56 and smooth muscle actin (SMA) are highly expressed in BCCs. We aimed to investigate the frequency of these markers, along with B-cell lymphoma 2 (Bcl-2) and Ki67. This study was conducted to propose a method that could possibly be of diagnostic value. One hundred twenty-eight BCC and 39 SCC cases were included in this study. CD56, SMA, Bcl-2, and Ki67 immunohistochemical stains were applied. Ninety-nine (77.3%) BCC and 6 (15.4%) SCC cases showed CD56 immunoreactivity. SMA expression was detected in 78.1% of BCC and 5.1% of SCC cases. CD56, SMA, and Bcl-2 expressions were significantly higher in BCC cases. The Ki67 proliferation index was found significantly higher in SCC cases. When basosquamous carcinoma cases were compared with SCC cases, a significant correlation between tumors and expression of CD56, SMA, and Bcl-2 were obtained. CD56 and SMA, in addition to Bcl-2, favor BCC. Ki67 should also be included in the panel to demonstrate the proliferative activity.
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Affiliation(s)
- Selin Yirmibes
- Department of Pathology, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey; and
| | - Saduman Balaban Adim
- Department of Pathology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
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Yirmibeş S, Adım ŞB, Saraydaroğlu Ö. CD56 and smooth muscle actin immunoreactivity in basal cell carcinomas: Are they indicators of differentiation or do they hold a diagnostic use? J Cutan Pathol 2023; 50:56-61. [PMID: 36054407 DOI: 10.1111/cup.14322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 08/17/2022] [Accepted: 08/28/2022] [Indexed: 01/03/2023]
Abstract
BACKGROUND Basal cell carcinoma (BCC) is the most common cutaneous malignancy and may show various differentiations. The possible pluripotent stem cell lineage of BCCs, whose origins are controversial today, is thought to be the main reason for the different morphologies. The aim of the study is to evaluate the expression of some neuroendocrine and smooth muscle markers of differentiation in BCCs and investigate the relationship between histopathologic subtypes and recurrence. METHODS A total of 128 cases diagnosed as BCC in our center were included. Immunohistochemical studies of CD56, synaptophysin, chromogranin-A, smooth muscle actin (SMA), desmin, caldesmon, and Ki67 were applied. RESULTS CD56, chromogranin-A, and synaptophysin immunoreactivity were detected in 77.3%, 13.3%, and 0.8% of the cases, respectively. 78.1% showed SMA positivity while no tumor expressed desmin or caldesmon. A correlation between histopathologic recurrence risk groups and CD56 expression was found (p < 0.05). CONCLUSIONS CD56 and SMA immunoreactivity is present in the majority of BCCs. However, the available findings do not support neuroendocrine or smooth muscle differentiation. CD56 antigen can be used for prognostic purposes in detecting high recurrence risk tumors. After the investigation of the expression rates of these two antigens in different cutaneous tumors, it may be appropriate to use them for diagnostic purposes in BCCs.
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Affiliation(s)
- Selin Yirmibeş
- Department of Pathology, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey
| | - Şaduman Balaban Adım
- Department of Pathology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
| | - Özlem Saraydaroğlu
- Department of Pathology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
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Gadelha MIP. Validade dos marcadores tumorais. REVISTA BRASILEIRA DE CANCEROLOGIA 2022. [DOI: 10.32635/2176-9745.rbc.1998v44n3.2813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Considerando-se o número crescente dos chamados marcadores tumorais e a sua incorporação sistemática à prática médica, procedeu-se a um levantamento, por meio de Medline® 1995, na Biblioteca Central do Instituto Nacional de Câncer - INCA, e revisão de 95 resumos de trabalhos publicados de 1995 a abril de 1997. Verificou-se que a validade dos marcadores é maior para o diagnóstico patológico de alguns tipos tumorais e determinação de alguns fatores prognósticos; que poucos são os de real utilidade clínica, seja para prevenção, diagnóstico ou prognóstico, vez que a maioria deles só alcança significância quando a doença já provoca algum sinal ou sintoma; que a maioria das referências correspondem, a rigor, a trabalhos repetidos, que avaliam os mesmos marcadores, embora em diferentes tumores; e que há trabalhos que se referem a poucos casos, quando não pouquíssimos, e cujos resultados tomam-se, por isso, inconsistentes. Neste artigo, os marcadores tumorais são classificados por tipos (genes, expressões genéticas, substâncias circulantes, substâncias celulares, receptores da membrana celular e índices de proliferação tumoral) e por finalidades (prevenção, detecção, diagnóstico, estadiamento, monitoração terapêutica, seguimento pós-tratamento e prognóstico) e são correlacionados com o(s) tumor(es) em que foram pesquisados. Apresentam-se três grupos de critérios de validação (estatísticos, biomédicos e por finalidades) e resume-se, a partir também de mais 16 outras referências bibliográficas, a utilidade de marcadores dos cânceres de mama [ADN, fração de Fase S, índice de ADN, C-erbB-2 (HER-2/neu), P53, CAT-D, CA15.3 e CEA - sem validade; marcadores tumorais hormonais - úteis para a indicação de hormonioterapia adjuvante ou paliativa]; colorretal [LASA, CA 19.9, índice de ADN, fração de Fase S, p53 e ras - sem validade; CEA-com validade para estadiamento e planejamento cirúrgico, e para seguimento pós-operatório (dosagem seriada a cada 2-3 meses por 2 anos, se houve suspeita de metástase hepática em estádios cirúrgicos II e III)] e de próstata (PSA com utilidade para a detecção, mas associado ao toque retal, em homens acima de 40-50 anos, como indicativos da necessidade de exames mais acurados, e para o seguimento dos casos tratados). E inquestionável a utilidade da dosagem de alfa-feto-proteína (aFP) e da gonadotrofina coriônica (hCG), para o estadiamento, tratamento, avaliação da resposta terapêutica e seguimento dos casos tratados de tumores testiculares (aFP e hCG) e de neoplasia trofoblástica gestacional (hCG). Também inquestionável é o papel da identificação dos marcadores de diferenciação celular no diagnóstico patológico de leucemias e linfomas. Os dilemas evidenciados a partir deste estudo referem-se a cinco binômios: 1) ausência de sinal ou sintoma versus positividade de marcador tumoral; 2) detecção de recidiva assintomática versus a qualidade e a quantidade da sobrevida do indivíduo; 3) natureza da causa versus aumento do marcador; 4) exame falso-positivo versus tratamento; e 5) baixo risco de evolução de neoplasia detectada versus tratamento. Conclui-se que, exceto pelos marcadores de validade estabelecida para o diagnóstico, o seguimento do tratamento ou o prognóstico dos casos de alguns cânceres, o médico precisa, além de conhecer os marcadores tumorais e suas siglas, saber os limites das suas indicações e ter opinião, crítica e método na sua utilização.
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Caspase-3, p53 and Bcl-2 expression in basal cell carcinoma of the eyelid. Postepy Dermatol Alergol 2020; 37:535-539. [PMID: 32994776 PMCID: PMC7507160 DOI: 10.5114/ada.2020.98285] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 01/21/2019] [Indexed: 01/10/2023] Open
Abstract
Introduction Eyelid tumours mostly originated from skin and its appendeges. External carcinogens like UV radiation causes cell damages in the eyelid skin and contributes to carcinogenesis. Apoptosis is a very important mechanism to prevent these damage and probable neoplatic change. Aim To compare caspase-3, p53 and Bcl-2 levels between patients with basal cell carcinoma (BCC) of the eyelid and healthy individuals. Material and methods Pathology archives from October 2012 to April 2015 were scanned for BCC biopsies of the eyelid and tissue removed during blepharoplasty and entropion procedures. A total of 36 specimens were found. The specimens were divided into two groups: BCC group and controls (consisting of eyelid tissue removed during routine blepharoplasty). The pathology specimens were then stained using p53, Bcl-2 and caspase-3 stains and the intensity of staining was graded on a 0–3 scale. Results Samples from a total of 36 patients were included in the study. Eighteen (50.0%) patients were female. There were 13 patients in the BCC group and 23 patients in the control group. The mean age was 66.0 ±10.8 years in the BCC group, and 65.61 ±11.22 years in the control group. The caspase-3 staining was lower in the BCC group than in the control group. No significant differences were found between the BCC group and the control group in terms of p53 levels or Bcl-2 levels (both of them, p = 1.000). Conclusions The caspase-3 level was lower in the BCC group. This result suggests that these enzymes can play a significant role in carcinogenesis of eyelid BCC.
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Proliferative Activity in Basal Cell Carcinomas. CURRENT HEALTH SCIENCES JOURNAL 2019; 44:55-60. [PMID: 30622756 PMCID: PMC6295187 DOI: 10.12865/chsj.44.01.09] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 01/13/2018] [Indexed: 11/18/2022]
Abstract
Basal cell carcinomas (BCCs) represent one of the most common human neoplasias. The excellent prognosis of the diagnosed early lesions and the low metastasis rate are particularities that required the investigation of the mechanisms of carcinogenesis on these lesions. In this study we analyzed the proliferation rate for 53 cases of BCC in relation to the clinicopathological parameters of the lesions using Ki67, considered a true indicator of cellular proliferation. The results indicated statistically significant differences in Ki67 immunoexpression related to histological type and lesion stage. The highest Ki67 values were observed in the adenoid and morpheaform subtypes, and in advanced tumor stages. This aspects may be useful for stratification of lesions in terms of tumor aggressiveness.
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Ferreli C, Lai C, August S, Buggy Y, Kumar P, Brownlow N, Parker P, Friedmann PS, Ardern-Jones M, Pickard C, Healy E. STAT4 expression and activation is increased during mitosis in vitro and in vivo in skin- and mucosa-derived cell types: implications in neoplastic and inflammatory skin diseases. J Eur Acad Dermatol Venereol 2017; 31:1663-1673. [PMID: 28516569 DOI: 10.1111/jdv.14342] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Accepted: 04/19/2017] [Indexed: 02/11/2024]
Abstract
BACKGROUND The signal transducer and activator of transcription-4 (STAT4/Stat4) is a transcription factor known to convey signals from interleukin-12, interleukin-23, and interferon-alpha/beta to the nucleus, resulting in activation of dendritic cells, T-helper cell differentiation and production of interferon-gamma. OBJECTIVE To demonstrate a novel role for STAT4 in cell mitosis. RESULTS Phosphoserine STAT4 (pSerSTAT4) is increased in cells undergoing mitosis and is distributed throughout the cytoplasm during this stage of the cell cycle, whilst phosphotyrosine STAT4 (pTyrSTAT4) is confined to the chromosomal compartment. This distinct pattern of pSerSTAT4 during mitosis is seen in vitro in human keratinocytes and in other cell types. This is also present in vivo in cells undergoing mitosis in normal skin, psoriasis and squamous cell carcinoma. Inhibition of STAT4 phosphorylation by lisofylline and depletion of STAT4 by RNA interference results in a delay in progression of mitosis and leads to a reduction in cells completing cytokinesis. CONCLUSION Our data demonstrate that STAT4 plays a role in enabling the normal and timely division of cells undergoing mitosis.
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Affiliation(s)
- C Ferreli
- Dermatopharmacology, Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK
- Dermatology Unit, Department of Medical Sciences, Public Health University of Cagliari, Cagliari, Italy
| | - C Lai
- Dermatopharmacology, Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK
- Dermatology, University Hospital Southampton NHS Foundation Trust, Southampton, Hampshire, UK
| | - S August
- Dermatopharmacology, Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK
- Dermatology, University Hospital Southampton NHS Foundation Trust, Southampton, Hampshire, UK
| | - Y Buggy
- Dermatopharmacology, Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK
| | - P Kumar
- Dermatopharmacology, Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK
| | - N Brownlow
- London Research Institute, Lincoln's Inn Fields, London, UK
| | - P Parker
- London Research Institute, Lincoln's Inn Fields, London, UK
| | - P S Friedmann
- Dermatopharmacology, Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK
- Dermatology, University Hospital Southampton NHS Foundation Trust, Southampton, Hampshire, UK
| | - M Ardern-Jones
- Dermatopharmacology, Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK
- Dermatology, University Hospital Southampton NHS Foundation Trust, Southampton, Hampshire, UK
| | - C Pickard
- Dermatopharmacology, Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK
| | - E Healy
- Dermatopharmacology, Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK
- Dermatology, University Hospital Southampton NHS Foundation Trust, Southampton, Hampshire, UK
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Jawad SN, Abdullah BH. Ameloblastoma vs basal cell carcinoma: an immunohistochemical comparison. Ann Diagn Pathol 2016; 25:79-84. [PMID: 27806852 DOI: 10.1016/j.anndiagpath.2016.09.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Despite behavioral mimicry of ameloblastoma (AB) and basal cell carcinoma (BCC), they are classified at 2 extremes within pertinent WHO classifications with respect to benign and malignant designation. This study aims to appraise the current allocation of AB in the classification through an immunohistochemical comparison of some aspects of behavior with BCC. Sections from retrospectively retrieved formalin-fixed, paraffin-embedded tissue blocks of AB (n = 37) and BCC (n = 34) were comparatively examined for the immunohistochemical expression for Ki-67, Bcl-2, MMP-2, MMP-9, CD31, and D2-40 monoclonal antibodies. No statistically significant differences between the tumors were found regarding the immunoexpressions of Bcl-2 (P = .252), CD31 microvessel density (P = .895), lymphatic vessel density (P = .642), and MMP-9 stromal expression (P = .083). MMP-2 expression was significantly higher in epithelial and stromal regions of AB (P = .009 and P = .001, respectively), whereas Ki-67 and MMP-9 epithelial expressions were significantly higher in BCC (P < .000 and P = .026, respectively). Within the studied immunohistochemical attributes for tumor behavior, the study accentuated the overall behavioral mimicry of the tumors and indicated that BCCs surmount ABs by the proliferative rate only.
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Affiliation(s)
- Salam N Jawad
- Oral pathology, College of Dentistry, Baghdad University, Baghdad, Iraq.
| | - Bashar H Abdullah
- Professor of Oral pathology, College of Dentistry, Baghdad University, Baghdad, Iraq
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Al Asmari AK, Khan AQ. Investigation of in vivo potential of scorpion venom against skin tumorigenesis in mice via targeting markers associated with cancer development. DRUG DESIGN DEVELOPMENT AND THERAPY 2016; 10:3387-3397. [PMID: 27799739 PMCID: PMC5076799 DOI: 10.2147/dddt.s113171] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Cancer is the leading cause of morbidity and mortality all over the world in spite of the advances made in its management. In this study, we investigated the in vivo anti-tumorigenic potential of the venom obtained from a medically important scorpion species Leiurus quinquestriatus on chemically induced skin cancer in mice. Animals were divided into five groups, with 13 animals in each group. All the treatments were given topically on the shaved dorsal surface of the skin. Animals in Group 1 received vehicle only (0.2 mL acetone). Moreover, 7,12-dimethylbenz[a]anthracene (DMBA, 400 nmol per mouse) was applied to all the animals in the remaining four groups. After 1 week, different concentrations of venom (17.5 μg, 35 μg, and 52.5 μg per animal) were applied to each animal in the Groups III–V. Thirty minutes after the application of venom, croton oil was applied on the same position where venom was administered to the animals of Groups III–V. Animals in Group II were treated as the positive control (without venom) and received croton oil as in Groups III–V. The findings of this study revealed that venom extract of L. quinquestriatus inhibits DMBA + croton oil-induced mouse skin tumor incidence and tumor multiplicity. Venom treatment also decreased the expression of proinflammatory cytokines. Immunohistochemistry results showed a downregulation of the expression of molecular markers such as Ki-67, nuclear factor kappa-B, cyclooxygenase-2, B-cell lymphoma-2, and vascular endothelial growth factor, in venom-treated animals. Our findings suggest that the venom of L. quinquestriatus possesses in vivo anticancer potential and may be used in the development of anticancer molecules.
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Khalesi M, Waterhouse M, Whiteman DC, Johns R, Rosendahl C, Hackett T, Pollak T, Kimlin MG, Hacker E, Neale RE. Comparison of PTCH1, COX-2, p53, and Ki-67 protein expression in basal cell carcinomas of nodular and superficial subtypes arising on the head and trunk. Int J Dermatol 2016; 55:1096-105. [PMID: 27126210 DOI: 10.1111/ijd.13276] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2015] [Revised: 11/11/2015] [Accepted: 12/04/2015] [Indexed: 12/21/2022]
Abstract
BACKGROUND There is some evidence that basal cell carcinomas (BCCs) arising on different anatomic sites and developing to different histological subtypes differ in their pathophysiology. The expression of a number of proteins, including PTCH1, COX-2, p53, and Ki-67, is frequently altered in BCC development. OBJECTIVES This study sought to determine whether protein expression differs between BCCs at different anatomic sites and of different histological subtypes. METHODS Expression of PTCH1, COX-2, p53, and Ki-67 proteins was compared between: (i) BCCs arising on the head (n = 55) and trunk (n = 53), and (ii) nodular (n = 52) and superficial (n = 43) BCCs. The intensity of immunohistochemistry (IHC) staining (low, moderate, strong, very strong) for PTCH1 and COX-2 proteins was measured and the proportions of p53- and Ki-67-positive cells quantified. RESULTS The proportion of cells expressing Ki-67 was higher in tumor tissue than in non-malignant epidermis, whereas the opposite was found for PTCH1. The IHC staining intensity for PTCH1 was substantially greater in truncal BCCs than in BCCs on the head (odds ratio [OR] 3.82, 95% confidence interval [CI] 1.63-8.96). The intensity of staining for PTCH1 was greater for superficial than for nodular BCCs (OR 3.70, 95% CI 1.53-8.97), and superficial BCCs showed a higher proportion of Ki-67-positive cells (OR 5.57, 95% CI 1.66-18.67). CONCLUSIONS These differences suggest that the pathophysiology of BCC differs between lesions on the head and trunk and between nodular and superficial subtypes, perhaps indicating differences in their etiology.
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Affiliation(s)
- Mohammad Khalesi
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld, Australia. , , .,Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia. , , .,NHMRC Centre for Research Excellence in Sun and Health (CRESH), Queensland University of Technology, Brisbane, Qld, Australia. , ,
| | - Mary Waterhouse
- Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia
| | - David C Whiteman
- Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia.,NHMRC Centre for Research Excellence in Sun and Health (CRESH), Queensland University of Technology, Brisbane, Qld, Australia
| | - Richard Johns
- Skin Cancer College Australasia, Brisbane, Qld, Australia
| | - Cliff Rosendahl
- Mayne Medical School, School of Medicine, University of Queensland, Brisbane, Qld, Australia
| | - Timothy Hackett
- Mayne Medical School, School of Medicine, University of Queensland, Brisbane, Qld, Australia
| | - Thomas Pollak
- Queensland Brain Institute, University of Queensland, Brisbane, Qld, Australia
| | - Michael G Kimlin
- NHMRC Centre for Research Excellence in Sun and Health (CRESH), Queensland University of Technology, Brisbane, Qld, Australia.,University of the Sunshine Coast, Sunshine Coast, Qld, Australia.,Cancer Council Queensland, Brisbane, Qld, Australia
| | - Elke Hacker
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld, Australia.,Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia
| | - Rachel E Neale
- Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia.,NHMRC Centre for Research Excellence in Sun and Health (CRESH), Queensland University of Technology, Brisbane, Qld, Australia
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Zhan WJ, Zhu JF, Wang LM. Inhibition of proliferation and induction of apoptosis in RB116 retinoblastoma cells by afatinib treatment. Tumour Biol 2016; 37:9249-54. [PMID: 26768746 DOI: 10.1007/s13277-015-4768-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2015] [Accepted: 12/29/2015] [Indexed: 01/26/2023] Open
Abstract
The present study investigates the effect of afatinib on the growth, induction of apoptosis in RB116 cells, and reduction of carcinoma growth in the mice transplanted with RB116 cells. The results from MTT assay revealed that afatinib inhibited the growth of RB116 cells in a dose-dependent manner. Proliferation of RB116 cells was reduced to 64 % on treatment with 200 μM concentration of afatinib after 48 h. Afatinib treatment of RB116 cells at 200 μM concentration induced apoptosis and necrosis in 49.7 and 9.4 %, respectively, after 48 h. In the RB116-transplanted mice, treatment with afatinib at 10-mg/kg doses for 45 days caused a significant (p < 0.005) reduction in the tumor volume compared to the control group. The tissue lysates of the mice containing RB116 transplant showed a significant decrease in the expressions of Ki67 and p53 in the afatinib treatment group after 45 days. However, the expression of caspase-3 was increased and of Bcl-2 remained unaltered on treatment with afatinib. Measurement of the body weight of afatinib-treated animals showed no reduction during the study. Thus, afatinib can be of therapeutic value for the treatment of retinoblastoma.
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Affiliation(s)
- Wei-Jiao Zhan
- Department of Ophthalmology, Linyi People's Hospital, No. 48, Jiefang Road, Lanshan District, Linyi, Shandong, 276000, China
| | - Jian-Feng Zhu
- Department of Ophthalmology, Linyi People's Hospital, No. 48, Jiefang Road, Lanshan District, Linyi, Shandong, 276000, China
| | - Long-Mei Wang
- Department of Ophthalmology, Linyi People's Hospital, No. 48, Jiefang Road, Lanshan District, Linyi, Shandong, 276000, China.
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Expression of matrix metalloproteinase-13 and Ki-67 in nonmelanoma skin cancer in xeroderma pigmentosum and non-xeroderma pigmentosum. Am J Dermatopathol 2013; 35:45-9. [PMID: 22722466 DOI: 10.1097/dad.0b013e31825aa334] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Xeroderma pigmentosum (XP) is a heterogenous group of genetic diseases in which basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer (NMSC) followed by squamous cell carcinoma (SCC). The aim of this study was to investigate the expression of matrix metalloproteinase (MMP)-13 and Ki-67 in SCC and BCC from patients with and without XP to elucidate their roles in the pathogenesis of these highly aggressive tumors in patients with XP. Immunolabeling using MMP-13 and Ki-67 antibodies was performed on tissue sections derived from skin biopsies of SCC and BCC of 15 patients with XP and 40 non-XP patients. There was no significant difference between XP and non-XP patients as regards MMP-13 expression by epithelial and stromal cells of SCC or BCC. Ki-67 expression in SCC and BCC of patients with XP was significantly higher than in non-XP patients. We concluded that the higher expression of Ki-67 in NMSC of patients with XP than of non-XP patients may reflect the growth and invasive capacity of these tumors in patients with XP. MMP-13 is expressed by tumor epithelial cells, stromal and inflammatory cells of NMSC of both XP and non-XP patients.
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12
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Khodaeiani E, Fakhrjou A, Amirnia M, Babaei-nezhad S, Taghvamanesh F, Razzagh-Karimi E, Alikhah H. Immunohistochemical evaluation of p53 and Ki67 expression in skin epithelial tumors. Indian J Dermatol 2013; 58:181-7. [PMID: 23723466 PMCID: PMC3667278 DOI: 10.4103/0019-5154.110824] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND AND AIMS The cellular mechanisms responsible for initiating or limiting the tumors including skin types are of great importance. The p53 is a tumor-inhibiting gene which is believed to be defective in many malignant situations. Ki67 is a non-histonic protein which is mainly interfere with the proliferation and has many controlling effects during the cell cycle. Because of their importance in skin tumor cell growth, this study aimed at evaluating the p53 and Ki67 expression in skin epithelial tumors by immunohistochemical method. MATERIALS AND METHODS In a descriptive setting, 50 biopsy samples (30 basal cell carcinomas (BCCs), 10 squamous cell carcinomas (SCCs), 8 keratoacanthomas (KAs), and 2 trichoepitheliomas (TEs)) were immunohistochemically evaluated for p53 and Ki67 expression during a 14-month period. The incidence and expression rate of these two variables were separately reported in each group of samples. RESULTS The expression rate of p53 was 67.77% for the BCCs, 50.20% for the SCCs, and null for the KAs. For both TEs, it was 50%. The expression rate of Ki67 was 57.33% for the BCCs, 47.70% for the SCCs, 37.5% for the KAs, and 0.0% for TEs. The incidence of P53+ cells was 100% and 90% in the BCC and SCC samples, respectively. The both TEs were positive in this regard. The incidence of Ki67+ cells was 100% for the BCC, SCC, and KA samples. The both TEs were negative in this regard. CONCLUSION This study showed that the incidence rate of p53- and Ki67-positive cells is very high in skin malignant epithelial tumors. The expression rate of these two variables is comparable with reports in the literature. Further studies with large sample size are recommended to be carried out for KA and TE samples.
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Affiliation(s)
| | - Ashraf Fakhrjou
- Department of Pathology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Amirnia
- From the Department of Dermatology, Sina Hospital, Tabriz, Iran
| | | | | | | | - Hossein Alikhah
- From the Department of Dermatology, Sina Hospital, Tabriz, Iran
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Theodoropoulou S, Brodowska K, Kayama M, Morizane Y, Miller JW, Gragoudas ES, Vavvas DG. Aminoimidazole carboxamide ribonucleotide (AICAR) inhibits the growth of retinoblastoma in vivo by decreasing angiogenesis and inducing apoptosis. PLoS One 2013; 8:e52852. [PMID: 23300996 PMCID: PMC3536763 DOI: 10.1371/journal.pone.0052852] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2011] [Accepted: 11/23/2012] [Indexed: 01/22/2023] Open
Abstract
5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), an analog of AMP is widely used as an activator of AMP-kinase (AMPK), a protein that regulates the responses of the cell to energy change. Recently, we showed that AICAR-induced AMPK activation inhibits the growth of retinoblastoma cells in vitro by decreasing cyclins and by inducing apoptosis and S-phase arrest. In this study, we investigated the effects of AMPK activator AICAR on the growth of retinoblastoma in vivo. Intraperitoneal injection of AICAR resulted in 48% growth inhibition of Y79 retinoblastoma cell tumors in mice. Tumors isolated from mice treated with AICAR had decreased expression of Ki67 and increased apoptotic cells (TUNEL positive) compared with the control. In addition, AICAR treatment suppressed significantly tumor vessel density and macrophage infiltration. We also showed that AICAR administration resulted in AMPK activation and mTOR pathway inhibition. Paradoxically observed down-regulation of p21, which indicates that p21 may have a novel function of an oncogene in retinoblastoma tumor. Our results indicate that AICAR treatment inhibited the growth of retinoblastoma tumor in vivo via AMPK/mTORC1 pathway and by apoptogenic, anti-proliferative, anti-angiogenesis mechanism. AICAR is a promising novel non-chemotherapeutic drug that may be effective as an adjuvant in treating Retinoblastoma.
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Affiliation(s)
- Sofia Theodoropoulou
- Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Retina Service, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Katarzyna Brodowska
- Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Retina Service, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Maki Kayama
- Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Retina Service, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Yuki Morizane
- Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Retina Service, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Joan W. Miller
- Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Retina Service, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Evangelos S. Gragoudas
- Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Retina Service, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Demetrios G. Vavvas
- Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Retina Service, Harvard Medical School, Boston, Massachusetts, United States of America
- * E-mail:
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Welsch MJ, Troiani BM, Hale L, DelTondo J, Helm KF, Clarke LE. Basal cell carcinoma characteristics as predictors of depth of invasion. J Am Acad Dermatol 2012; 67:47-53. [DOI: 10.1016/j.jaad.2011.02.035] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2010] [Revised: 11/19/2010] [Accepted: 02/18/2011] [Indexed: 02/03/2023]
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Immunohistochemical evaluation of proliferative activity (Ki-67 index) in different histological types of cutaneous basal cell carcinoma. Biologia (Bratisl) 2012. [DOI: 10.2478/s11756-012-0035-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Pacella A, Andreozzi GB, Fournier J, Stievano L, Giantomassi F, Lucarini G, Rippo MR, Pugnaloni A. Iron topochemistry and surface reactivity of amphibole asbestos: relations with in vitro toxicity. Anal Bioanal Chem 2011; 402:871-81. [DOI: 10.1007/s00216-011-5525-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2011] [Revised: 10/17/2011] [Accepted: 10/19/2011] [Indexed: 11/25/2022]
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Abstract
This study was set to investigate the relation between autophagic activity and the aggressiveness of cutaneous squamous cell carcinomas (SCC), as indicated by tumor thickness and proliferative activity. The anti-LC3A antibody, recognizing both the soluble and the autophagosome-bound forms of the protein, and a standard immunohistochemical technique were applied to 75 cutaneous SCC of variable tumor thickness. The study was complemented by staining for MIB1. Three patterns of LC3A reactivity were recognized: diffuse cytoplasmic, cytoplasmic/perinuclear, and "stone-like" structures (SLS), that is, large, rounded, densely stained amorphous material, 5 μm on average, enclosed within cytoplasmic vacuoles. Higher numbers of SLS were counted in >6-mm-thick SCC compared with the intermediate-thickness tumors (2.1-6 mm) and the <2-mm-thick tumors; the mean recorded values, being 8.8, 4.55, and 1.55, respectively, were statistically significant. The diffuse cytoplasmic staining showed a nearly inverse trend, whereas the perinuclear pattern, expressed in <10% of the total, was not evaluated. With regard to MIB1 proliferation index, this increased with tumor thickness and, in linear regression analysis, was directly linked with SLS counts and inversely with the cytoplasmic pattern. These data suggest that autophagic activity in SCC, when expressed as high LC3A/SLS counts, can be regarded as an indicator of tumor aggressiveness.
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Karakok M, Turkmen A, Bekerecioglu M, Emrah Koçer N. Immunohistochemical prognostic criteria in xeroderma pigmentosum. Int J Dermatol 2010; 49:1266-71. [DOI: 10.1111/j.1365-4632.2009.04382.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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20
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Biological effects and comparative cytotoxicity of thermal transformed asbestos-containing materials in a human alveolar epithelial cell line. Toxicol In Vitro 2010; 24:1521-31. [DOI: 10.1016/j.tiv.2010.07.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2010] [Revised: 06/14/2010] [Accepted: 07/09/2010] [Indexed: 11/23/2022]
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Koseoglu RD, Sezer E, Eyibilen A, Aladag I, Etikan I. Expressions of p53, cyclinD1 and histopathological features in basal cell carcinomas. J Cutan Pathol 2009; 36:958-65. [PMID: 19187116 DOI: 10.1111/j.1600-0560.2008.01204.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND We planned this study to analyze probable associations between p53, cyclinD1, Ki67 and histopathological features in basal cell carcinomas (BCC). METHODS Histological differentiation types, histological growth patterns and tissue responses were analyzed in 50 cases of BCC. In immunohistochemical analysis, p53, cyclinD1 and Ki67 antibodies were investigated. P53 expression was evaluated based on a cut-off value of 25% positivity. CyclinD1 expression was graded from 0 to 3+ according to the percentage of positive nuclear staining. The percentage of positively staining cells for Ki67 was recorded. RESULTS The following significant correlations were detected. Solid infiltrative type differentiation was related to the infiltrative histological growth pattern. The rates of p53 positivity and severe fibrosis in the groups of mixed and infiltrative growth patterns were higher than others. Besides, p53-positive cases showed more severe fibrosis and had a higher mean value for Ki67 index. Epidermal p53 and cyclinD1 clones in normal epidermal areas adjacent to tumors were noticed in 42% and 52% of the cases, respectively. CONCLUSIONS P53 expression seems to be related to Ki67 index and some histopathological features of BCC, such as infiltrative histological growth pattern and probably fibrosis.
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Affiliation(s)
- Resit D Koseoglu
- Department of Pathology, Gaziosmanpasa University School of Medicine, Tokat, Turkey.
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Koseoglu RD, Sezer E, Eyibilen A, Aladag I, Etikan I. Expressions of p53, cyclinD1 and histopathological features in basal cell carcinomas. J Cutan Pathol 2009. [DOI: 10.1111/j.1600-0560.2009.01204.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Son KD, Kim TJ, Lee YS, Park GS, Han KT, Lim JS, Kang CS. Comparative analysis of immunohistochemical markers with invasiveness and histologic differentiation in squamous cell carcinoma and basal cell carcinoma of the skin. J Surg Oncol 2008; 97:615-20. [PMID: 18404670 DOI: 10.1002/jso.21006] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND This study evaluates several tumor-related markers to examine the expression pattern of markers according to the invasiveness and histopathologic differentiation of squamous cell carcinoma and basal cell carcinoma. METHODS Ninety-four cases of squamous cell carcinoma and 108 cases of basal cell carcinoma using tissue array in order to determine correlations between the expression of Ki-67, p53, EGFR, CD44v6, MMP-1 and MMP-3, invasiveness and histologic differentiation. In order to determine invasiveness, we measured the depth of invasion in resected tissues. RESULTS The depth of invasion showed a correlation with CD44v6 expression of tumor cell in both squamous cell carcinoma and basal cell carcinoma (P = 0.009, P = 0.036, respectively) and with the MMP-1 expression of stromal cell in squamous cell carcinoma (P = 0.010). The differentiation of squamous cell carcinoma was correlated with Ki-67 index. The loss of palisading arrangement in basal cell carcinoma was correlated with the MMP-1 expression of stromal cells (P = 0.045). CONCLUSIONS CD44v6 and MMP-1, expressed in tumor cells and stromal cells respectively, are significant markers associated with the invasiveness of tumors in squamous cell carcinoma and basal cell carcinoma of the skin and that it will be helpful to evaluate the invasiveness by measuring the expression of these markers.
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Affiliation(s)
- Kyung Dong Son
- Department of Plastic and Reconstructive Surgery, Kangnam St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Janisson-Dargaud D, Durlach A, Lorenzato M, Grange F, Bernard P, Birembaut P. Aneuploidy, but not Ki-67 or EGFR expression, is associated with recurrences in basal cell carcinoma. J Cutan Pathol 2008; 35:916-21. [PMID: 18537864 DOI: 10.1111/j.1600-0560.2007.00935.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Basal cell carcinoma (BCC), the most common skin cancer, has an overall excellent prognosis, but recurrences are frequent. The value of classical clinical and histological prognostic factors to predict recurrences remain limited. METHODS In order to evaluate the prognostic value of Epidermal Growth Factor Receptor (EGFR) expression, Ki-67 antigen expression and DNA ploidy, we compared primary tumors in 20 patients who had subsequent local recurrences and 20 matched controls without recurrences. DNA ploidy was determined by image cytometry, and EGFR and Ki-67 expression were studied by immunohistochemistry. RESULTS Statistical analysis of the intensity and the percentage of EGFR expression and Ki-67 antigen expression did not show any significant difference between the two groups. In contrast, we found that 78% of primary BCC in patients who experienced recurrences vs. 32% in the control group were aneuploid (p = 0.005). CONCLUSIONS Aneuploidy is a risk factor for recurrences. This factor should be useful in clinical practice and require evaluation in further studies.
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Bordbar A, Dias D, Cabral A, Beck S, Boon ME. Assessment of Cell Proliferation in Benign, Premalignant and Malignant Skin Lesions. Appl Immunohistochem Mol Morphol 2007; 15:229-35. [PMID: 17525640 DOI: 10.1097/01.pai.0000209867.20581.c7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
A deeper understanding of the variance of epidermal cell proliferation may eventually increase the reproducibility of diagnostic classification. A prospective study of 46 consecutive, unselected biopsies from benign (keratoacanthoma n=14), premalignant (actinic keratosis n=15 and Bowen disease n=10) and malignant (squamous cell carcinoma n=7) skin lesions was studied to assess the presence and extent of differences in expression of the proliferation marker Ki-67 using a monoclonal antibody directed against a c-DNA defined subsegment (MIB-1) and a noncross-linking, proprietary fixative BoonFix. MIB-1 was expressed in the adjacent, non-affected skin in a scattered to confluent linear pattern in the basal/suprabasal cell layer. In actinic keratosis, MIB-1 expression, in addition to basal/suprabasal layers, extended to mid-zones of the epidermis. An interesting feature in actinic keratosis as well as in Bowen disease was the expression of MIB-1 in the epithelium lining the hair follicles. In Bowen disease, MIB-1 was observed throughout the full thickness of the epidermis, unequivocally separating this entity from others under study. In invasive squamous cell carcinoma, MIB-1 expression was not consistent between and within cases. MIB-1 positivity was variably found in all layers of the epidermis, but showed a chaotic and haphazard pattern with total loss of polarity. Keratoacanthoma cases showed highly variable MIB-1 expression, ranging from no expression to expression in both basal/suprabasal and mid-zone layers of the epidermis. These results warrant further study of modulation of cell proliferation in actinic keratosis.
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Affiliation(s)
- Arash Bordbar
- Leiden Cytology and Pathology Laboratory, Leiden, The Netherlands
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O'Driscoll L, McMorrow J, Doolan P, McKiernan E, Mehta JP, Ryan E, Gammell P, Joyce H, O'Donovan N, Walsh N, Clynes M. Investigation of the molecular profile of basal cell carcinoma using whole genome microarrays. Mol Cancer 2006; 5:74. [PMID: 17173689 PMCID: PMC1770933 DOI: 10.1186/1476-4598-5-74] [Citation(s) in RCA: 298] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2006] [Accepted: 12/15/2006] [Indexed: 11/25/2022] Open
Abstract
Background Skin cancer accounts for 1/3 of all newly diagnosed cancer. Although seldom fatal, basal cell carcinoma (BCC) is associated with severe disfigurement and morbidity. BCC has a unique interest for researchers, as although it is often locally invasive, it rarely metastasises. This paper, reporting the first whole genome expression microarray analysis of skin cancer, aimed to investigate the molecular profile of BCC in comparison to non-cancerous skin biopsies. RNA from BCC and normal skin specimens was analysed using Affymetrix whole genome microarrays. A Welch t-test was applied to data normalised using dCHIP to identify significant differentially-expressed genes between BCC and normal specimens. Principal component analysis and support vector machine analysis were performed on resulting genelists, Genmapp was used to identify pathways affected, and GOstat aided identification of areas of gene ontology more highly represented on these lists than would be expected by chance. Results Following normalisation, specimens clustered into groups of BCC specimens and of normal skin specimens. Of the 54,675 gene transcripts/variants analysed, 3,921 were differentially expressed between BCC and normal skin specimens. Of these, 2,108 were significantly up-regulated and 1,813 were statistically significantly down-regulated in BCCs. Conclusion Functional gene sets differentially expressed include those involved in transcription, proliferation, cell motility, apoptosis and metabolism. As expected, members of the Wnt and hedgehog pathways were found to be significantly different between BCC and normal specimens, as were many previously undescribed changes in gene expression between normal and BCC specimens, including basonuclin2 and mrp9. Quantitative-PCR analysis confirmed our microarray results, identifying novel potential biomarkers for BCC.
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Affiliation(s)
- Lorraine O'Driscoll
- National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
| | - Jason McMorrow
- National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
| | - Padraig Doolan
- National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
| | - Eadaoin McKiernan
- National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
| | - Jai Prakash Mehta
- National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
| | - Eoin Ryan
- National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
| | - Patrick Gammell
- National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
| | - Helena Joyce
- National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
| | - Norma O'Donovan
- National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
| | - Nicholas Walsh
- Bons Secours Hospital, Dublin 9 & Blackrock Clinic, Dublin 4, Ireland
| | - Martin Clynes
- National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
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Tucci MG, Lucarini G, Giangiacomi M, Zizzi A, Criante P, Ricotti G, Biagini G. Immunohistochemical study of apoptosis markers and involvement of chemokine CXCR4 in skin Merkel cell carcinoma. J Eur Acad Dermatol Venereol 2006; 20:1220-5. [PMID: 17062035 DOI: 10.1111/j.1468-3083.2006.01764.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Merkel cell carcinoma (MCC) is a rare, aggressive cancer of the skin that mainly affects elderly patients. Because of its rarity, there is no established treatment or proven markers to guide therapy or prognosis. Immunohistochemical expression of apoptosis proteins is considered a useful marker of both malignancy and tumour progression. Apoptosis plays a fundamental role in skin homeostasis, and apoptotic cells have been detected in normal and diseased skin. Chemokines possess a wide range of biological activities and CXCR4 is expressed in some cancer cells, where it plays an efficient role in metastasis formation. OBJECTIVE To identify immunohistochemical parameters that can help clinicians select the most suitable therapy for skin MCC. DESIGN Antibodies against ki67, bcl-2, p53, survivin, p16 and CXCR4 were tested to assess the usefulness of these antigens as indices of proliferation potential and predictors of prognosis. METHODS Immunohistochemical detection of apoptosis inhibitors and CXCR4 was performed on tissue from 12 patients with primary MCC. After excision of the primary lesion, five survived and had no metastases, and seven experienced local recurrence or lymph node metastases. RESULTS Expression of ki67 and survivin was increased in patients with local recurrence or metastasis (retrospectively classified as 'poor prognosis') compared with those with a 'good prognosis', and bcl-2 expression was significantly greater (P=0.003). P53 and p16 immunostaining was moderate in both groups. A positive correlation was observed between survivin and mutant p53 in the poor prognosis group (r=0.593, P=0.033; regression coefficient). High values of p53 were measured in patients with high levels of survivin and vice versa. CXCR4 was not detected at all. CONCLUSIONS Our results show strong MCC cell apoptosis inhibition and a high cell proliferation capacity. The positive correlation between survivin and p53 may be a predictor of MCC spread via the lymphatic network. Absent CXCR4 expression may reflect a less aggressive form, with less efficient development of distant and non-organ-selective metastasis formation.
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Affiliation(s)
- M G Tucci
- U.O. Dermatologia, INRCA-IRCCS, Ancona, Italy
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Ionescu DN, Arida M, Jukic DM. Metastatic basal cell carcinoma: four case reports, review of literature, and immunohistochemical evaluation. Arch Pathol Lab Med 2006; 130:45-51. [PMID: 16390237 DOI: 10.5858/2006-130-45-mbccfc] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT Metastatic basal cell carcinoma (BCC) is relatively rare and is seldom considered a complication in the routine treatment and follow-up of patients with BCC. Although multiple studies have tried to distinguish aggressive from nonaggressive BCCs, to our knowledge, no consistent clinical, histopathologic, or immunohistochemical features have yet been reported. OBJECTIVE To report 4 cases of metastatic BCCs and to evaluate these in addition to known nonmetastatic BCCs with specific immunostains in an attempt to find distinct morphologic or immunohistochemical patterns that could be helpful in identifying aggressive BCCs. DESIGN We reviewed 4 cases of metastatic BCCs and recorded the clinical and morphologic findings. We then searched our archives for 14 cases of BCC that followed the usual nonaggressive course. We evaluated these 18 cases with immunohistochemical stains for Ki-67, p53, and bcl-2. RESULTS In metastasizing BCC, Ki-67 staining was slightly higher in metastatic sites than in primary sites (average 63% and 51%, respectively). p53 was expressed in 3 of 4 primary sites and 2 of 4 metastatic sites. Bcl-2 was positive in both primary and metastatic sites in 3 of 4 cases. In the 14 cases of nonaggressive BCC, staining for Ki-67 averaged 38%, p53 was positive in 11 cases, and Bcl-2 staining was noted in 13 cases. CONCLUSIONS Overall, in the small sample that we evaluated, the immunohistochemical markers for Ki-67, p53, and Bcl-2 did not distinguish between metastatic and nonaggressive BCCs.
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Affiliation(s)
- Diana N Ionescu
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA
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Vidal D, Matías-Guiu X, Alomar A. Efficacy of imiquimod for the expression of Bcl-2, Ki67, p53 and basal cell carcinoma apoptosis. Br J Dermatol 2004; 151:656-62. [PMID: 15377354 DOI: 10.1111/j.1365-2133.2004.06094.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
BACKGROUND Imiquimod is a modifier of the immune response that has been proven to be an effective treatment for basal cell carcinoma (BCC). However, its mechanism of action is still unknown. OBJECTIVES To determine whether imiquimod modifies the expression of proteins such as Bcl-2, Ki67, p53 and the BCC apoptotic index. PATIENTS AND METHODS Thirty caucasian patients with primary BCCs larger than 8 mm in diameter were included in a double-blind randomized clinical and immunohistochemical study which was designed in a reference university hospital. The 30 BCCs were randomized in two treatment arms between September 2001 and February 2002. Twenty-four BCCs were treated with imiquimod 5% cream and six BCCs with Aldara (3M Pharmaceuticals) excipient. Histological samples were obtained before treatment and on days 8 and 15 during the course of treatment. The BCC expression of Bcl-2, Ki67 and p53 was determined in paraffin samples and the apoptotic index of the BCC was studied using the TUNEL technique (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labelling) in frozen samples. All variables were evaluated quantitatively in fields with a magnification x 400. RESULTS The BCCs treated with imiquimod showed a decrease in the expression of Bcl-2 (88.7% before treatment, 61.4% day 15, P = 0.01) and an increase in the apoptotic index (0.53% before treatment, 1.66% day 15, P = 0.002), which were not observed in the BCCs treated with the excipient. Ki67 and p53 did not show significant changes in any group. CONCLUSIONS Imiquimod reduces the expression of Bcl-2 in the BCC cells and increases the BCC apoptotic index.
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Affiliation(s)
- D Vidal
- Dermatology Unit, Hospital de la Santa Creu i Sant Pau, C/Sant Antoni Maria Claret 167, Barcelona 08025, Spain.
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Mazzarelli P, Rabitti C, Parrella P, Seripa D, Persichetti P, Marangi GF, Perrone G, Poeta ML, Delfino M, Fazio VM. Differential modulation of Ku70/80 DNA-binding activity in a patient with multiple basal cell carcinomas. J Invest Dermatol 2003; 121:628-33. [PMID: 12925225 DOI: 10.1046/j.1523-1747.2003.12416.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Ku70/80 nonhomologous end-joining activity is essential for resolving random DNA double-strand breaks, and the Ku70/80 protein complex has been proposed as "caretaker" of genomic stability. We studied the Ku70/80 heterodimer activity in a patient affected by multiple basal cell carcinomas with a personal history of moderate exposure to ionizing radiation. The Ku70/80 DNA-binding activity was analyzed, by electrophoretic mobility shift assay, in five tumor biopsies from different sites and at distinct clinical stages, and in three matched normal skin samples from the same patient. As control normal tissues from healthy individuals were also tested. The five basal cell carcinomas were classified as "non aggressive" and "aggressive" on the basis of morphologic parameters and expression of the molecular markers bcl-2, Ki67/MIB1, and p53. A 62% increase in the Ku70/80 DNA-binding activity was found in normal skin from the patient, compared to unexposed individuals (p<0.0001). The nuclear activity of the heterodimer was further increased in nonaggressive basal cell carcinomas compared to both matched normal skin from the patient (31%, p=0.0001) and tissues from healthy controls (73%, p=0.0001). Strikingly, the two aggressive basal cell carcinomas tested showed very low Ku70/80 DNA-binding activity with a reduction of 87% compared to normal skin from the patient (p<0.0001) and 64% compared to controls (p=0.001). Although these results are limited to only one patient, together with other recent studies they support the hypothesis that downregulation of the nonhomologous end-joining pathway may be associated with tumor progression.
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Affiliation(s)
- Paola Mazzarelli
- Laboratory for Molecular Medicine and Biotechnology, Interdisciplinary Center for Biomedical Research, Università Campus Bio-Medico, Rome, Italy
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Ellis PE, Fong LFWT, Rolfe KJ, Crow JC, Reid WMN, Davidson T, MacLean AB, Perrett CW. The role of p53 and Ki67 in Paget's disease of the vulva and the breast. Gynecol Oncol 2002; 86:150-6. [PMID: 12144821 DOI: 10.1006/gyno.2002.6629] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
OBJECTIVE Paget's disease of the vulva (PDV) and Paget's disease of the breast (PDB) are uncommon diseases, accounting for approximately 1% of all vulval neoplasms and 0.5-4% of all breast cancers, respectively. In 10-30% of vulval cases an invasive adenocarcinoma is present. In such cases the disease is often aggressive and recurrence rate is high. This is in contrast to PDB where the general consensus is that almost all cases are associated with an in situ or invasive ductal carcinoma. Our aim was to examine the presence of the tumor suppressor protein p53 and the proliferation marker Ki67 in PDV and PDB and correlate any differences in the expression of these two proteins with the presence of an underlying carcinoma. METHODS Immunohistochemistry was performed on 52 archival cases of PDV, which included 10 with associated invasive adenocarcinoma of the vulva, and on 37 archival cases of PDB, including 26 with available associated ductal carcinoma in situ (DCIS) or invasive carcinoma of the breast. All cases were formalin-fixed and paraffin wax-embedded. Monoclonal antibodies were used with microwave antigen retrieval. Streptavidin-biotin-horseradish peroxidase and 3,3'-diaminobenzidine detection methods were employed to visualize antibody binding and staining. A section was scored positive for p53 if more than 10% of cell nuclei were stained brown and Ki67 was expressed as a percentage of positive cells to the nearest 5% of cells showing nuclear positivity (Ki67 staining index). RESULTS p53 was expressed in 15 of 52 (29%) PDV cases and 5 of 37 (13%) cases of PDB. Four of the ten cases (40%) of PDV associated with invasive disease expressed p53 compared with 11 of 42 (26%) cases without invasive disease. The mean Ki67 staining index for PDV associated with invasion was 19%, and for that without invasion, 16%. In the breast cases, the mean staining index was 11%. CONCLUSION Our data suggest that p53 may have a role to play in PDV progression, and may be a late event in some cases, especially those associated with invasive disease. Ki67 has no apparent prognostic role in PDV as there was no significant difference between those cases associated with and those without invasive disease. Neither p53 nor Ki67 appears to have a prognostic role to play in PDB.
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Affiliation(s)
- P E Ellis
- Department of Obstetrics and Gynaecology, Royal Free & University College Medical School (Royal Free Campus), London, United Kingdom
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Auepemkiate S, Boonyaphiphat P, Thongsuksai P. p53 expression related to the aggressive infiltrative histopathological feature of basal cell carcinoma. Histopathology 2002; 40:568-73. [PMID: 12047769 DOI: 10.1046/j.1365-2559.2002.01393.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
AIMS To determine whether the p53 protein expression which is involved in the genesis and progression of various malignant tumours may relate to age, sites or the aggressive histopathological feature of the basal cell carcinoma. METHODS ADN RESULTS: One hundred and fifty-eight basal cell carcinoma specimens from Songklanakarind Hospital, southern Thailand, collected from January 1992 to December 2000, were examined by immunohistochemistry using polyclonal anti-p53-CM1 (Novocastra Laboratories, Newcastle, UK; dilution 1:700). p53 protein expression was demonstrated in 48.7% of cases. The multivariate analysis showed that the aggressive infiltrative histopathological type was significantly associated with p53 expression (odds ratio 2.95, 95% confidence interval 1.10-7.90), whereas age, sun-exposure site, cellular response and fibrosis were not. CONCLUSIONS The p53 expression is found to be related to the aggressive histopathological feature, which may be of predictive value for the behaviour of basal cell carcinoma. However, this result does not support the relation between sun exposure inducing basal cell carcinoma and p53 protein expression.
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Affiliation(s)
- Sauvarat Auepemkiate
- Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla Province, Thailand.
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Murphy M, Carlson JA. Can we reliably use markers of cell cycle regulation (e.g. Ki-67, p21, p27, p53) to differentiate between benign and malignant skin tumors? J Cutan Pathol 2001; 28:219-21. [PMID: 11426830 DOI: 10.1034/j.1600-0560.2001.028004219.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Li LX, Crotty KA, McCarthy SW, Palmer AA, Kril JJ. A zonal comparison of MIB1-Ki67 immunoreactivity in benign and malignant melanocytic lesions. Am J Dermatopathol 2000; 22:489-95. [PMID: 11190439 DOI: 10.1097/00000372-200012000-00002] [Citation(s) in RCA: 86] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Differentiation between malignant melanomas and benign nevi can sometimes be difficult by conventional histopathology, and additional diagnostic markers may be helpful. This study investigated the immunoreactivity of the cell proliferation marker MIB1-Ki67 in 23 compound nevi, 17 dysplastic nevi, 8 Spitz nevi (SN), and 24 malignant melanomas (MMs) and evaluated its ability in separating benign nevi from MMs. In each lesion, the average number (percentage) of MIB1-positive nuclei (%MIB1-Mean) and the maximal number (percentage) of MIB1-positive nuclei (%MIB1-Max) were determined from each of the superficial, middle, and deep dermal zones of the lesion as well as from the entire lesion. The %MIB1-Max was determined from subjectively selected area(s) of high count. Malignant melanomas had a significantly greater %MIB1-Mean and %MIB1-Max than all benign nevi in all individual zones and in the entire lesion (p < 0.05). Discriminant analysis showed that the %MIB1-Mean and %MIB1-Max counted from the whole lesions had better discriminating abilities than from the individual zones. By using the %MIB1-Mean from all zones, all lesions except 1 SN and 3 MMs could be correctly classified as benign or malignant. When using the %MIB1-Max from all zones, all but 2 SN could be correctly separated as benign or malignant. Thus, MIB1-Ki67 immunoreactivity closely correlates with the benignancy or malignancy of melanocytic lesions and may assist in the differentiation of benign nevi from MMs.
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MESH Headings
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Antigens, Neoplasm/analysis
- Antigens, Nuclear
- Biomarkers, Tumor/analysis
- Child
- Child, Preschool
- Diagnosis, Differential
- Female
- Humans
- Immunoenzyme Techniques
- Ki-67 Antigen/analysis
- Male
- Melanoma/chemistry
- Melanoma/pathology
- Middle Aged
- Nevus, Epithelioid and Spindle Cell/chemistry
- Nevus, Epithelioid and Spindle Cell/pathology
- Nevus, Pigmented/chemistry
- Nevus, Pigmented/pathology
- Nuclear Proteins/analysis
- Skin Neoplasms/chemistry
- Skin Neoplasms/pathology
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Affiliation(s)
- L X Li
- Department of Pathology, University of Sydney, and Centre for Education and Research on Ageing, Concord Hospital, New South Wales, Australia
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Saridaki Z, Koumantaki E, Liloglou T, Sourvinos G, Papadopoulos O, Zoras O, Spandidos DA. High frequency of loss of heterozygosity on chromosome region 9p21-p22 but lack of p16INK4a/p19ARF mutations in greek patients with basal cell carcinoma of the skin. J Invest Dermatol 2000; 115:719-25. [PMID: 10998150 DOI: 10.1046/j.1523-1747.2000.00098.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Basal cell carcinoma of the skin is the most common neoplasia in humans. Previous studies have shown the existence of allelic imbalance (loss of heterozygosity and microsatellite instability) in BCC on several human chromosomes. Chromosome region 9p21-p22 harbors the CDKN2a/p16INK4a, p19ARF, and p15INK4b tumor suppressor genes. To determine the contribution of these genes to the development of basal cell carcinomas we looked for evidence of allelic imbalance in 67 sporadic basal cell carcinoma specimens from Greek patients and screened 28 of them presenting loss of heterozygosity at 9p21-p22 for germline mutations in p16INK4a and p19ARF genes. Chromosome regions 17q21 and 17p13 were also screened for allelic imbalance in all the 67 basal cell carcinoma specimens. Overall, 69% (46 of 67) of the specimens displayed loss of heterozygosity in at least one microsatellite marker, whereas only six of the 67 (9%) exhibited microsatellite instability. For the 9p21-p22 locus the overall frequency of loss of heterozygosity reached 55% (37 of 67) and is the highest reported. The overall frequency of loss of heterozygosity for the 17q21 locus is 34% (22 of 64) and for the 17p13 locus is 11% (seven of 65). Two of the 28 loss of heterozygosity positive cases were heterozygous for a previously described polymorphism, Ala148Thr, in exon 2 of the CDKN2a gene. This is the first demonstration of polymorphism in the CDKN2a gene in human basal cell carcinomas. No sequence variation in exon 1beta of the p19ARF gene was found. Our results provide evidence of a significantly high occurrence of loss of heterozygosity for the 9p21-p22 locus; however, lack of p16INK4a/p19ARF mutation suggests that these genes seem not to be implicated by mutational inactivation in the development of basal cell carcinoma. Other(s), yet unidentified, tumor suppressor gene(s) located in this locus may be related to this specific type of skin cancer.
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Affiliation(s)
- Z Saridaki
- Laboratory of Virology, Medical School, University of Crete, Heraklion, Greece
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Fernández-Aceñero MJ, Manzarbeitia F, Mestre MJ, Requena L. p53 expression in two cases of spiradenocarcinomas. Am J Dermatopathol 2000; 22:104-107. [PMID: 10770428 DOI: 10.1097/00000372-200004000-00003] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
p53 protein is a nuclear 53-kDa phosphoprotein that acts as a suppressor protein. There are several studies on the expression of p53 in skin tumors, but few deal with adnexal malignant tumors because of their rarity. We performed immunohistochemistry for the detection of p53 and Ki-67 in two cases of malignant spiradenomas and six cases of spiradenomas retrieved from our files. In our cases, p53 was expressed only in the malignant areas of the lesions, whereas the benign areas of the spiradenocarcinomas and all the spiradenomas were negative (nuclear positivity <10%). These results seem to support the idea that p53 is implicated in the malignant transformation of adnexal tumors.
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MESH Headings
- Adenocarcinoma/chemistry
- Adenocarcinoma/metabolism
- Adenocarcinoma/pathology
- Adenocarcinoma/surgery
- Adenoma, Sweat Gland/chemistry
- Adenoma, Sweat Gland/metabolism
- Adenoma, Sweat Gland/pathology
- Adenoma, Sweat Gland/surgery
- Aged
- Aged, 80 and over
- Cell Nucleus/metabolism
- Cell Nucleus/pathology
- Cell Transformation, Neoplastic
- Humans
- Immunoenzyme Techniques
- Ki-67 Antigen/analysis
- Ki-67 Antigen/metabolism
- Male
- Neoplasms, Multiple Primary/chemistry
- Neoplasms, Multiple Primary/metabolism
- Neoplasms, Multiple Primary/pathology
- Neoplasms, Multiple Primary/surgery
- Sweat Gland Neoplasms/chemistry
- Sweat Gland Neoplasms/metabolism
- Sweat Gland Neoplasms/pathology
- Sweat Gland Neoplasms/surgery
- Tumor Suppressor Protein p53/analysis
- Tumor Suppressor Protein p53/metabolism
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Tabata H, Nagano T, Ray AJ, Flanagan N, Birch-MacHin MA, Rees JL. Low frequency of genetic change in p53 immunopositive clones in human epidermis. J Invest Dermatol 1999; 113:972-6. [PMID: 10594739 DOI: 10.1038/sj.jid.5600549.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Sun-exposed skin of Caucasians harbors thousands of p53-mutated clones, which are clinically invisible. Using whole mount immunostaining for p53 or Ki67 antigens, p53 sequencing, and loss of heterozygosity analysis, we have further characterised these clones. Loss of heterozygosity for the alleles examined is uncommon with the exception of 9q, which occurred in 28.3% of the samples. P53 clones are more common and larger in individuals with basal cell carcinoma than in control subjects (p < 0.03). Loss of heterozygosity is also more common in clones from individuals with basal cell carcinoma than in clones from subjects without a history of basal cell carcinoma, as would be expected if both relate to ultraviolet radiation exposure. p53 sequencing of clones is in keeping with the mutagenic role of ultraviolet radiation. Surprisingly, skin found to harbor p53 clones showed no clusters of Ki67 positive cells, unlike the situation for actinic keratoses or basal cell carcinomas. These results show that in human skin p53 mutation is not directly associated with genomic instability or abnormal cell cycling; that the p53 immunopositive clones are either genetically distinct or precursors to other squamous cell lesions of skin; and that p53 immunopositive clones are early lesions, in that gross disturbance of proliferation has not already occurred.
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Affiliation(s)
- H Tabata
- Department of Dermatology, Medical School, University of Newcastle, UK
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Horlock N, Wilson GD, Daley FM, Richman PI, Grobbelaar AO, Sanders R, Foy C. Cellular proliferation characteristics do not account for the behaviour of horrifying basal cell carcinoma. A comparison of the growth fraction of horrifying and non horrifying tumours. BRITISH JOURNAL OF PLASTIC SURGERY 1998; 51:59-66. [PMID: 9577321 DOI: 10.1054/bjps.1997.0031] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This study compared the clinical features, histological subtype, growth fraction (by Ki67 immunohistochemistry) and proliferation pattern of 22 clinically defined horrifying basal cell carcinoma compared to 81 non horrifying lesions. Late presentation was associated with half of the horrifying tumours. The other half developed horrifying tumours despite early intervention. The horrifying tumours exhibited a variety of histological growth patterns. A total of 50% were infiltrative, 23% nodular and 18% micronodular. There was no difference in the growth fraction or proliferation pattern between horrifying and non horrifying tumours of similar growth pattern (P = ns), although infiltrative tumours in either group exhibited a significantly higher growth fraction than nodular tumours (P < 0.01). This suggests that there is no intrinsic biological difference between horrifying and non horrifying tumours to account for their behaviour. We conclude that late presentation, failed or inadequate early management especially of infiltrative tumours (and other subtypes) determines the development of horrifying tumours.
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Affiliation(s)
- N Horlock
- RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Northwood, Middlesex, UK
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40
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Horlock NM, Wilson GD, Daley FM, Richman PI, Sanders R. Cellular proliferation characteristics of basal cell carcinoma: relationship to clinical subtype and histopathology. Eur J Surg Oncol 1997; 23:247-52. [PMID: 9236901 DOI: 10.1016/s0748-7983(97)92508-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
This study investigates the proliferation characteristics of 81 primary basal cell carcinomas (BCC) using detection of the Ki-67 antigen by immunohistochemistry. The tumours were classified into distinct sub-types based on their histological growth pattern and differentiation status. The mean Ki-67 growth fraction was 0.293 and this was found to vary between the different growth patterns, with morpheic, infiltrating and superficial tumours showing the highest levels of proliferation at 0.373, 0.351 and 0.335, respectively; the nodular and micronodular growth patterns were significantly lower at 0.248 and 0.232, respectively. No overall association was seen between proliferation and differentiation status although certain histological growth patterns such as nodular showed a greater propensity to differentiate. Proliferation was related to tumour size, with larger lesions exhibiting higher growth fractions although this may have also been related to tumour subtype as infiltrating and morpheic tumours tended to present with larger tumour diameters. The spatial distribution of proliferating cells by Ki-67 labelling was not related to tumour subtype, differentiation or growth fraction. These studies have shown BCC to possess proliferative characteristics akin to other solid tumours commonly regarded as more rapidly dividing. There was an association between growth fraction and tumour subtype consistent with higher proliferation in the lesions considered to be more aggressive.
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Affiliation(s)
- N M Horlock
- RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Northwood, Middlesex, UK
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Kanitakis J, Narvaez D, Euvrard S, Faure M, Claudy A. Proliferation markers Ki67 and PCNA in cutaneous squamous cell carcinomas: lack of prognostic value. Br J Dermatol 1997; 136:643-4. [PMID: 9155986 DOI: 10.1111/j.1365-2133.1997.tb02173.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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Rossen K, Haerslev T, Hou-Jensen K, Jacobsen GK. Bcl-2 overexpression in basaloid proliferations overlying dermatofibromas and basal cell carcinomas. APMIS 1997; 105:35-40. [PMID: 9063499 DOI: 10.1111/j.1699-0463.1997.tb00537.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Basaloid proliferations overlying dermatofibromas resembling superficial basal cell carcinomas have been interpreted both as reactive/regressive and frankly malignant. Basal cell carcinoma is a slow-growing tumour, which so far has been regarded as an actively proliferating lesion with a high apoptotic activity. We examined immunohistochemically 6,dermatofibromas with overlying simple hyperplasia, 12 dermatofibromas with overlying basaloid proliferations, and 24 basal cell carcinomas for expression of Ki-67 protein, and bcl-2 protein. The Ki-67 labelling index represents an estimate of proliferative activity. Bcl-2 protein suppresses apoptosis. The Ki-67 labelling indexes of basaloid proliferations, basal cell carcinomas, and normal epidermis were similar (11-15%, p < 0.05, Mann-Whitney test). Bcl-2 protein was expressed in all cells of basaloid proliferations, similar to the expression pattern in basal cell carcinomas. We suggest that basaloid proliferations overlying dermatofibromas might have achieved a phenotype that equals an early stage of BCC carcinogenesis.
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Affiliation(s)
- K Rossen
- Department of Pathology, Gentofte University Hospital, Hellerup, Denmark
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