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Chen Y, Fang C, Huang J, Pan H, He L, Zhuang C, Zheng X. The correlation between the main and minor lesions of synchronous multiple gastric neoplasms assessed gastroscopically and microscopically. Surg Endosc 2024; 38:1211-1221. [PMID: 38092970 DOI: 10.1007/s00464-023-10624-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 11/29/2023] [Indexed: 02/23/2024]
Abstract
BACKGROUND Patients with early gastric cancer (EGC) are at high risk of developing synchronous multiple gastric neoplasms (SMGNs) after undergoing endoscopic submucosal dissection (ESD). However, most previous studies have had small sample sizes, and few have focused on association studies. AIMS This study aimed to analyze the associations between SMGN lesion data from patients with EGC treated with ESD and their correlation coefficients. METHODS The clinical ESD data from two hospitals from January 2008 to January 2021 were retrospectively analyzed. The main lesions were defined as those with a significant depth of infiltration. The larger tumor diameter was considered the main lesion if the lesions had the same infiltration depth. RESULTS Of the 1013 post-ESD cases examined, 95 cases (223 lesions) had SMGN, and 25 patients had more than three lesions. For the correlation analysis, 190 lesions were included. The study revealed a similarity in pathological type between main and minor lesions (rs = 0.37) and a positive correlation in infiltration depth (rs = 0.58). The mean diameter sizes of the main and minor lesions were 20.7 ± 8.3 mm and 13.1 ± 6.4 mm, respectively, with statistically significant differences (P < 0.001). A linear correlation was observed between the diameter size and a linear regression model was constructed, producing r = 0.38 [95% confidence interval (CI) 0.19-0.54], b = 0.29 (95% CI 0.14-0.44), t = 3.94, P < 0.001]. A correlation was identified between the vertical distribution of the main and minor lesions, the horizontal distribution, and the gross endoscopic morphology (ϕc = 0.25, P = 0.02; ϕc = 0.32, P < 0.001; ϕc = 0.60, P < 0.001). CONCLUSIONS The correlation coefficients for microscopic characteristics were higher than those for gastroscopy. There is a significant positive correlation between the main and minor lesions regarding pathological stage and depth of infiltration, respectively. The spatial distribution of the lesions and the gastroscopic morphology were similar.
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Affiliation(s)
- Yudai Chen
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China
- Department of Digestive Endoscopy, Fujian Provincial Hospital South Branch, Fuzhou, 350028, China
| | - Chaoying Fang
- Department of Digestive Endoscopy, Fujian Provincial Hospital South Branch, Fuzhou, 350028, China
| | - Jianmin Huang
- Department of Digestive Endoscopy, Fujian Provincial Hospital South Branch, Fuzhou, 350028, China
| | - Hui Pan
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China
- Department of Digestive Endoscopy, Fujian Provincial Hospital South Branch, Fuzhou, 350028, China
| | - Liping He
- Department of Digestive Endoscopy, Fujian Provincial Hospital South Branch, Fuzhou, 350028, China
| | - Chenlin Zhuang
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China.
- Department of Medicine, Fujian Provincial Hospital, Fuzhou, 350001, China.
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350028, China.
| | - Xiaoling Zheng
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China.
- Department of Digestive Endoscopy, Fujian Provincial Hospital, Fuzhou, 350001, China.
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350028, China.
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Lu M, Zhang X, Chu Q, Chen Y, Zhang P. Susceptibility Genes Associated with Multiple Primary Cancers. Cancers (Basel) 2023; 15:5788. [PMID: 38136334 PMCID: PMC10741435 DOI: 10.3390/cancers15245788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 11/29/2023] [Accepted: 12/05/2023] [Indexed: 12/24/2023] Open
Abstract
With advancements in treatment and screening techniques, we have been witnessing an era where more cancer survivors harbor multiple primary cancers (MPCs), affecting approximately one in six patients. Identifying MPCs is crucial for tumor staging and subsequent treatment choices. However, the current clinicopathological criteria for clinical application are limited and insufficient, making it challenging to differentiate them from recurrences or metastases. The emergence of next-generation sequencing (NGS) technology has provided a genetic perspective for defining multiple primary cancers. Researchers have found that, when considering multiple tumor pairs, it is crucial not only to examine well-known essential mutations like MLH1/MSH2, EGFR, PTEN, BRCA1/2, CHEK2, and TP53 mutations but also to explore certain pleiotropic loci. Moreover, specific deleterious mutations may serve as regulatory factors in second cancer development following treatment. This review aims to discuss these susceptibility genes and provide an explanation of their functions based on the signaling pathway background. Additionally, the association network between genetic signatures and different tumor pairs will be summarized.
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Affiliation(s)
| | | | | | | | - Peng Zhang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (M.L.)
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Zhao ZY, Lai YX, Xu P. Gastric ectopic pancreas combined with synchronous multiple early gastric cancer: A rare case report. World J Clin Cases 2023; 11:1569-1575. [PMID: 36926392 PMCID: PMC10011978 DOI: 10.12998/wjcc.v11.i7.1569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 01/13/2023] [Accepted: 02/15/2023] [Indexed: 03/02/2023] Open
Abstract
BACKGROUND A large percentage of patients with ectopic pancreas are asymptomatic. When present, the symptoms are typically non-specific. These lesions are predominantly located in the stomach and benign in nature. Synchronous multiple early gastric cancer (SMEGC) (two or more simultaneous malignant lesions with early gastric cancer) is relatively rare and particularly easy to overlook during endoscopic examination. The prognosis of SMEGC is generally poor. We report a rare case of ectopic pancreas with concomitant SMEGC.
CASE SUMMARY A 74-year-old woman presented with paroxysmal upper abdominal pain. On initial investigations, she tested positive for Helicobacter pylori (H. pylori). She underwent esophagogastroduodenoscopy which revealed a 1.5 cm × 2 cm major lesion at the greater curvature and a 1 cm minor lesion at the lesser curvature of the stomach. On endoscopic ultrasound, the major lesion showed hypoechoic changes, uneven internal echoes and unclear boundaries between some areas and the muscularis propria. Endoscopic submucosal dissection was performed to excise the minor lesion. A laparoscopic resection was chosen for the major lesion. On histopathological examination, the major lesion contained high grade intraepithelial neoplasia with a small focus of cancer. A separate underlying ectopic pancreas was found under this lesion. The minor lesion contained high grade intraepithelial neoplasia. In this case, the patient was diagnosed with SMEGC with concomitant ectopic pancreas in the stomach.
CONCLUSION Patients with atrophy, H. pylori, and other risk factors should be carefully investigated to avoid missing other lesions including SMEGC and ectopic pancreas.
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Affiliation(s)
- Zhen-Ya Zhao
- Department of Gastroenterology, Songjiang Hospital Affiliated to Shanghai Jiaotong University School of Medicine (Preparatory Stage), Shanghai 201600, China
| | - Yue-Xing Lai
- Department of Gastroenterology, Songjiang Hospital Affiliated to Shanghai Jiaotong University School of Medicine (Preparatory Stage), Shanghai 201600, China
| | - Ping Xu
- Department of Gastroenterology, Songjiang Hospital Affiliated to Shanghai Jiaotong University School of Medicine (Preparatory Stage), Shanghai 201600, China
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Wen T, Wang W, Chen X. Recent advances in esophageal squamous cell precancerous conditions: A review. Medicine (Baltimore) 2022; 101:e32192. [PMID: 36550838 PMCID: PMC9771210 DOI: 10.1097/md.0000000000032192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a common cancer in many developing countries in Asia and Africa, with a 5-year survival rate of approximately 20%. Most cases are diagnosed at an advanced age when there is no effective treatment strategy. Esophageal precancerous conditions have a much better prognosis, with a 5-year survival rate of over 90% by endoscopic diagnosis and treatment. Nevertheless, limitations, contraindications, and lymph node metastasis incompetency of endoscopy. Thus, the diagnosis and treatment of esophageal precancerous lesions remain a significant challenge. Biomarker investigations provide opportunities for target detection and therapy. Additionally, drug development is ongoing. Changes in lifestyle habits, such as diet balance, smoking and alcohol cessation, are beneficial for the prognosis of esophageal precancerous lesions. Collectively, multiple and sequential diagnoses and treatments are essential for curing esophageal precancerous lesions and reducing the incidence and mortality of ESCC.
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Affiliation(s)
- Tianjiao Wen
- Pharmacy Department, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China
| | - Wei Wang
- Department of clinical laboratory, Hebei General Hospital, Shijiazhuang, Hebei, PR China
| | - Xinran Chen
- Pharmacy Department, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China
- * Correspondence: Xinran Chen, Pharmacy Department, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, PR China (e-mail: )
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Zhao X, Xiong D, Luo S, Duan L. Molecular investigation of the dual inhibition mechanism for targeted P53 regulator MDM2/MDMX inhibitors. Phys Chem Chem Phys 2022; 24:16799-16815. [PMID: 35775962 DOI: 10.1039/d2cp01780f] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Inhibitors that competitively bind MDM2/MDMX can block the inhibition of P53 by MDM2/MDMX and restart its tumor-suppressive effect. Molecular studies targeting MDM2/MDMX inhibitors have always been a hot topic in anticancer drug design. Although numerous inhibitors have been designed previously against MDM2/MDMX, their dual inhibition efficacy has not been demonstrated, and few studies assessed the general causes affecting the dual inhibition of MDM2/MDMX by these inhibitors. Here, molecular dynamics simulations and alanine scanning combined with the interaction entropy method were employed to precisely investigate whether 16 inhibitors could dually inhibit MDM2/MDMX and the similarities and differences in the interaction modes. Thereby addressing the key residue sites affecting dual inhibition. Residues L54/M53, I61/60, M62/61, Y67/66, and V93/92 of MDM2/MDMX, which are in corresponding positions in both protein structures, provide significant conditions for these inhibitors to bind to MDM2/MDMX tightly. In addition, most of these inhibitors prefer to bind MDM2 than MDMX, and residues H96 and I99 in MDM2 are attractive targets for inhibitors, resulting in inhibitors binding to MDM2/MDMX with different affinity. These key residues should be considered in the development of dual inhibitors. For these 16 inhibitors, most have dual inhibitory potential for MDM2/MDMX based on the binding affinity of the complexes. Still, it is questionable whether they can exert excellent dual inhibition considering the assessment of the hot-spots. At least their binding affinity for MDMX is not superior to that for MDM2 due to the difference in energy of the van der Waals interactions at the key sites. Furthermore, based on the analysis of three representative inhibitors (TUZ/HRH and HRQ with different binding preferences for MDM2/MDMX), 3-chloropyridine in TUZ leads to the differential binding affinity between the inhibitor and MDM2/MDMX. It readily forms hydrophobic interactions with the surrounding residues H96 and I99. But this phenomenon does not occur in the TUZ-MDMX system, implying the critical role of residues H96/P95 and I99/L98. And the completely different binding mechanism of HRQ binding to MDM2/MDMX explains its inability to inhibit MDM2 well. Thus, we are cautious about its dual inhibitory ability. Besides, HRH is more prone to strong van der Waals interactions with MDM2 than MDMX whereas its 2-chlorofluorobenzene is detrimental to this. We hope that these findings will provide reliable molecular insights for the screening and optimization of targeting MDM2/MDMX dual inhibitors.
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Affiliation(s)
- Xiaoyu Zhao
- School of Physics and Electronics, Shandong Normal University, Jinan, 250014, China.
| | - Danyang Xiong
- School of Physics and Electronics, Shandong Normal University, Jinan, 250014, China.
| | - Song Luo
- School of Physics and Electronics, Shandong Normal University, Jinan, 250014, China.
| | - Lili Duan
- School of Physics and Electronics, Shandong Normal University, Jinan, 250014, China.
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Incidence of Multiple Metachronous Gastric Cancers After Pyloric-Preserving Gastrectomy. World J Surg 2021; 44:2719-2727. [PMID: 32266453 DOI: 10.1007/s00268-020-05492-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
AIM Pylorus-preserving gastrectomy (PPG) is widely used for early gastric cancer located in the middle third of the stomach. The minimization of the extent of gastrectomy may increase the risk of metachronous multiple gastric cancer (MGC). We report the findings of a study that was conducted to evaluate the prevalence of MGC after PPG. METHODS The clinical data of 533 patients who underwent PPG for gastric cancer between 1993 and 2018 were reviewed. The clinicopathological characteristics at the time of the primary treatment that were predictive of the development of MGC were explored. The median (range) observation period was 112.4 (8.1-290.7) months. RESULTS Metachronous MGC was diagnosed in 33 of the 533 patients. The cumulative 5-year and 10-year event rates were 3.3% and 6.2%, respectively. The patient gender, presence/absence of synchronous MGC and the macroscopic type of the primary gastric cancer were significantly associated with the risk of development of metachronous MGC. Multivariate analysis identified the presence of synchronous MGC (hazard ratio [HR]: 4.828, 95% confidence interval [CI]; 1.611-12.30, p = 0.004) and Type 0-IIa primary gastric cancer (HR 2.810, 95% CI; 1.113-7.090, p = 0.029) as independent factors associated with the risk of development of MGC. All the patients could be treated by surgical or endoscopic resection for the metachronous MGC. Recurrence was observed in one patient. CONCLUSIONS There was quite a few incidence of development of metachronous MGC after PPG. Nevertheless, PPG remains reasonable treatment option, if adequate postoperative surveillance can be ensured.
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Fukahori M, Kato K, Taniguchi H, Ohtomo R, Takahashi N, Shoji H, Iwasa S, Honma Y, Takashima A, Hamaguchi T, Yamada Y, Shimada Y, Ito Y, Itami J, Hokamura N, Igaki H, Tachimori Y, Miwa K, Torimura T, Boku N. Relationship between cervical esophageal squamous cell carcinoma and human papilloma virus infection and gene mutations. Mol Clin Oncol 2020; 14:41. [PMID: 33437479 PMCID: PMC7788557 DOI: 10.3892/mco.2020.2205] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Accepted: 10/27/2020] [Indexed: 12/29/2022] Open
Abstract
Cervical esophageal squamous cell carcinoma (CESCC) is rare, accounting for 5% of all esophageal carcinomas. Several diagnostic and predictive markers have been studied. However, to the best of our knowledge, no biomarker is known to determine patient management except the clinical stage. The present study aimed to evaluate whether human papilloma virus (HPV) infection, epidermal growth factor receptor (EGFR) and its pathway-related gene mutations, known to be sensitive biomarkers of oropharyngeal carcinomas, could be used as biomarkers for the prediction of the prognosis of patients with CESCC. The present retrospective study included patients with CESCC who received chemoradiotherapy or surgery. HPV infection and the genomic status of EGFR, KRAS, BRAF, NRAS and PIK3CA of each tumor sample from patients with CESCC were analyzed by in situ hybridizations (ISH) and PCR methods, respectively. The present study included 33 patients with CESCC (male/female, 29/4; median age, 62 years; age range, 41-86 years; clinical stage I/II/III/IV, 2/6/10/15). The present study detected HPV in one patient (3.0%) by ISH and PCR. Concerning the investigation of EGFR and its pathway-related gene mutations, the present study detected 15.1% of EGFR, 6.0% of NRAS, 3.5% of BRAF, 3.0% of KRAS and 3.0% for PIK3CA mutations, with no significant relationship between any gene mutations and the clinical prognostic factors. The HPV-infected patient did not exhibit any gene mutations. The present study indicated that HPV infection, EGFR and its pathway-related gene mutations rarely exist in patients with CESCC. The relationship between these biomarkers and the prognosis in patients with CESCC is still unclear.
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Affiliation(s)
- Masaru Fukahori
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.,Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan.,Division of Gastroenterology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Ken Kato
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Hirokazu Taniguchi
- Department of Clinical Laboratory, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Rie Ohtomo
- Department of Clinical Laboratory, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.,Department of Clinical Laboratory, JR Tokyo General Hospital, Shibuya, Tokyo 151-8528, Japan
| | - Naoki Takahashi
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Hirokazu Shoji
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Satoru Iwasa
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Yoshitaka Honma
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Atsuo Takashima
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Tetsuya Hamaguchi
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Yasuhide Yamada
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Yasuhiro Shimada
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Yoshinori Ito
- Department of Radiation Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Jun Itami
- Department of Radiation Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Nobukazu Hokamura
- Department of Esophageal Surgery, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Hiroyasu Igaki
- Department of Esophageal Surgery, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Yuji Tachimori
- Department of Esophageal Surgery, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
| | - Keisuke Miwa
- Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Narikazu Boku
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan
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Efficacy of Different Chemotherapy Regimens in Patients with Locally Advanced Synchronous Esophageal and Head/Neck Squamous Cell Carcinoma Receiving Curative Concurrent Chemoradiotherapy. J Clin Med 2020; 9:jcm9010197. [PMID: 31936858 PMCID: PMC7020070 DOI: 10.3390/jcm9010197] [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: 11/29/2019] [Revised: 12/15/2019] [Accepted: 01/07/2020] [Indexed: 12/14/2022] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) are very common cancers worldwide, and there is higher incidence of synchronous ESCC/NSCC in Taiwan. The aim of the current study was to investigate the efficacy of different chemotherapy regimens in patients with locally advanced synchronous ESCC/HNSCC who received curative concurrent chemoradiotheapy (CCRT). A total of 75 patients were identified and assigned to one of two groups: 45 patients receiving cisplatin/5-fluorouracil (5-FU) regime in one group and 30 patients receiving a weekly cisplatin regime in the other. Overall survival (OS) was calculated from the date of diagnosis of the ESCC or HNSCC to the date of death from any cause or the most recent follow-up. Kaplan–Meier curves and log-rank tests were used to estimate OS and differences between the two groups, respectively. There was no significant difference in the analysis of OS between the cisplatin/5-FU and the weekly cisplatin groups. However, patients that interrupted their CCRT were found to have worse OS compared to those without interruptions (5.4 months versus 18.8 months, p = 0.002). In subgroup analysis, patients without interruptions of CCRT had a better OS than those with interruptions in the cisplatin/5-FU group (13.0 months versus 5.4 months, p = 0.041) as well as in the weekly cisplatin group (21.4 months versus 5.0 months, p = 0.017). Interruption of CCRT was the only independently poor prognostic factor of OS in the univariate and multivariate (hazard ratio 0.18, p < 0.001) analyses. Most interruption of CCRT resulted from adverse events (AEs) or serious AEs. Although there was no significant difference in the incidence of AEs between these two groups, lower incidence of adverse events was mentioned in the weekly cisplatin group. Our study suggests that interruption of CCRT is an independently poor prognostic factor of OS, and that completion of CCRT without interruption is more important than the choice of chemotherapeutic regimen for patients with synchronous ESCC/HNSCC.
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Long noncoding RNA PANDA promotes esophageal squamous carcinoma cell progress by dissociating from NF-YA but interact with SAFA. Pathol Res Pract 2019; 215:152604. [DOI: 10.1016/j.prp.2019.152604] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 08/03/2019] [Accepted: 08/16/2019] [Indexed: 12/15/2022]
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Ueki N, Akazawa Y, Miura S, Matsuda K, Kurohama H, Imaizumi T, Kondo H, Nakashima M. Significant association between 53 BP1 expression and grade of intraepithelial neoplasia of esophagus: Alteration during esophageal carcinogenesis. Pathol Res Pract 2019; 215:152601. [PMID: 31570283 DOI: 10.1016/j.prp.2019.152601] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 08/02/2019] [Accepted: 08/16/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Abnormal DNA damage response (DDR) leads to genomic instability and carcinogenesis. P53-binding protein 1 (53 BP1), a DDR molecule, is known to accumulate at the sites of DNA double-strand breaks. The aim of this study was to analyze the expression pattern of 53 BP1-nuclear foci (NF) in esophageal neoplasms in order to visualize the state of DDR in esophageal carcinogenesis and to clarify its significance in the molecular pathology of the disease. METHODS A total of 61 lesions from 22 surgically resected samples of esophageal cancer, including histologically normal squamous epithelium, low-grade intraepithelial neoplasia (LG-IN), high-grade intraepithelial neoplasia (HG-IN), carcinoma in situ (CIS), and invasive squamous cell carcinoma (SCC), were included in the study. 53 BP1 and Ki-67 expression were analyzed by double-labeled immunofluorescence. RESULTS The number of discrete 53 BP1-NF increased as the tumor progressed from normal epithelium through LG-IN, HG-IN, CIS, and SCC. 53 BP1-NF larger than 1 μm in diameter (large foci), indicating intensive DDR, also showed a stepwise increase during the progression of carcinogenesis. Of note, large foci of 53 BP1 were found in significantly higher numbers in HG-IN than in LG-IN. Furthermore, localization of 53 BP1-NF in Ki-67-positive cells, indicating the abnormal timing of DDR, also increased with malignancy progression. CONCLUSIONS 53 BP1-NF accumulation increases during cancer progression from LG-IN to HG-IN to CIS to SCC. Detection of 53 BP1-NF by immunofluorescence, especially large foci, is a feasible method of estimating DNA instability and the malignant potential of esophageal intraepithelial neoplasia.
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Affiliation(s)
- Nozomi Ueki
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
| | - Yuko Akazawa
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
| | - Shiro Miura
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
| | - Katsuya Matsuda
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
| | - Hirokazu Kurohama
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
| | - Toshinobu Imaizumi
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
| | - Hisayoshi Kondo
- Biostatistics Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
| | - Masahiro Nakashima
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
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Baba Y, Yoshida N, Kinoshita K, Iwatsuki M, Yamashita YI, Chikamoto A, Watanabe M, Baba H. Clinical and Prognostic Features of Patients With Esophageal Cancer and Multiple Primary Cancers: A Retrospective Single-institution Study. Ann Surg 2019; 267:478-483. [PMID: 28151796 DOI: 10.1097/sla.0000000000002118] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE To investigate the clinical and prognostic characteristics of patients with esophageal cancer and multiple primary cancers. SUMMARY BACKGROUND DATA Patients with esophageal cancer frequently have multiple primary cancers, the presence of which may complicate physicians' decision-making because the clinical and prognostic features of such patients remain unknown. METHODS This retrospective single-institution study included 538 consecutive patients who had undergone resection of esophageal cancer. The Cox proportional hazard model was used to compute the hazard ratio (HR) for mortality. RESULTS At the time of surgery, 163 patients (30%) had multiple primary cancers (77, metachronous; 86, synchronous). Multiple primary cancers were significantly associated with alcohol use and tobacco smoking (Brinkman index). Patients with synchronous cancers had significantly shorter overall survival than those without multiple primary cancers (log-rank P = 0.032; univariate HR = 1.53, 95% confidence interval 1.02-2.17, P = 0.040; multivariate HR: 1.61; 95% confidence interval: 1.08-2.36; P = 0.020). Patients with metachronous cancers had similar prognoses to those without multiple primary cancers. The prognostic effect of synchronous cancers on overall survival was particularly prominent in patients with Stage I esophageal cancer (log-rank P = 0.0002). CONCLUSIONS Multiple primary cancers are associated with a history of tobacco and alcohol use, supporting the concept of field cancerization. Synchronous multiple primary cancers may be an independent predictor of poorer long-term survival in patients undergoing resection of esophageal cancers.
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Affiliation(s)
- Yoshifumi Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Naoya Yoshida
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Koichi Kinoshita
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Yo-Ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Masayuki Watanabe
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
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Chen YH, Lu HI, Chien CY, Lo CM, Wang YM, Chou SY, Su YY, Shih LH, Li SH. Treatment Outcomes of Patients with Locally Advanced Synchronous Esophageal and Head/Neck Squamous Cell Carcinoma Receiving Curative Concurrent Chemoradiotherapy. Sci Rep 2017; 7:41785. [PMID: 28134308 PMCID: PMC5278381 DOI: 10.1038/srep41785] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Accepted: 12/28/2016] [Indexed: 12/18/2022] Open
Abstract
The present study investigated clinical outcomes and prognostic factors of patients with locally advanced synchronous esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) receiving curative concurrent chemoradiotherapy (CCRT), and determined whether synchronous ESCC/HNSCC patients had worse prognosis compared to isolated ESCC patients. Using propensity score matching method, we compared 60 locally advanced synchronous ESCC/HNSCC patients with 60 matched isolated ESCC patients. Compared to 60 matched isolated ESCC patients, synchronous ESCC/HNSCC patients had significantly worse prognosis (13.5 months versus 17.2 months, P = 0.01), more grade 3-4 CCRT toxicity, and higher percentage of CCRT interruption. For synchronous ESCC/HNSCC group, the 1-year and 2-year survival rates were 52% and 13%, respectively. Univariate analysis showed that early ESCC stage, non-T4b disease, and salvage operations were significantly associated with superior survival. In multivariate analysis, ESCC stage represented an independent prognosticator. For chemotherapy regimen during CCRT, cisplatin/5-fluorouracil had significantly more grade 3-4 mucositis/esophagitis and neutropenia than weekly cisplatin. In conclusion, synchronous ESCC/HNSCC patients receiving curative CCRT have worse prognosis and poorer compliance of CCRT compared to isolated ESCC patients. For these patients, ESCC stage and T4b disease were significantly associated with clinical outcomes, and salvage operation may improve overall survival.
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Affiliation(s)
- Yen-Hao Chen
- Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taiwan
| | - Hung-I. Lu
- Department of Thoracic & Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Yen Chien
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Ming Lo
- Department of Thoracic & Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Ming Wang
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Shang-Yu Chou
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yan-Ye Su
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Li-Hsueh Shih
- Department of Nursing, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Shau-Hsuan Li
- Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Wang L, Yu X, Li J, Zhang Z, Hou J, Li F. Prognostic significance of p53 expression in patients with esophageal cancer: a meta-analysis. BMC Cancer 2016; 16:373. [PMID: 27370310 PMCID: PMC4930564 DOI: 10.1186/s12885-016-2427-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 06/27/2016] [Indexed: 02/06/2023] Open
Abstract
Background The prognostic value of p53 protein expression in esophageal cancer has been evaluated, but the results remain inconclusive and no consensus has yet been achieved. This meta-analysis was conducted to quantitatively assess the prognostic significance of p53 expression in esophageal cancer. Methods Publications that assessed the clinical or prognostic significance of p53 expression in esophageal cancer and were published before July 1, 2015 were identified by searching the PubMed and EMBASE databases. A meta-analysis was performed to clarify the association between p53 expression and the clinical outcomes. Results A total of 36 publications met the criteria and included 4577 cases. Analysis of these data showed that p53 expression in esophageal cancer was significantly associated with poorer 5-year survival (RR = 1.30, 95 % CI: 1.11–1.51, P = 0.0008). Subgroup analyses according to histological type, continent of the patients, and cut-off value revealed the similar results. The results also indicated that p53 expression was highly associated with advanced TNM stages (I/II vs. III/IV, OR = 0.74, 95 % CI: 0.55–0.99, P = 0.04), lymph node metastasis (OR = 0.77, 95 % CI: 0.66–0.90, P = 0.001), and distant metastasis (OR = 0.46, 95 % CI: 0.26–0.80, P = 0.006). However, p53 expression in the included studies was not significantly associated with tumor size (≤ 5 cm vs. > 5 cm, OR = 1.13, 95 % CI: 0.92–1.40, P = 0.24), tumor location (upper + middle vs. lower, OR = 0.91, 95 % CI: 0.70–1.17, P = 0.45), grade of differentiation (well + moderate vs. poor, OR = 1.10, 95 % CI: 0.90–1.34, P = 0.35), and the depth of invasion (T1/T2 vs. T3/T4, OR = 0.86, 95 % CI: 0.71–1.03, P = 0.09). Conclusions This meta-analysis showed that p53 expression may be a useful biomarker for predicting poorer prognosis in patients with esophageal cancer.
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Affiliation(s)
- Lianghai Wang
- Department of Pathology and Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Xiaodan Yu
- Department of Pathology and Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Jing Li
- Department of Pathology and Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Zhiyu Zhang
- Department of Pathology and Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Jun Hou
- Department of Immunology, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
| | - Feng Li
- Department of Pathology and Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China. .,Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
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14
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Hoeben A, Polak J, Van De Voorde L, Hoebers F, Grabsch HI, de Vos-Geelen J. Cervical esophageal cancer: a gap in cancer knowledge. Ann Oncol 2016; 27:1664-74. [PMID: 27117535 DOI: 10.1093/annonc/mdw183] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Accepted: 04/20/2016] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND The aim of this systematic review is to provide an overview of the diagnosis, treatment options and treatment-related complications of cervical esophageal carcinoma (CEC) and to subsequently provide recommendations to improve quality of care. DESIGN Studies were identified in PubMed, EMBASE and Web of Science. A total of 107 publications fulfilled the inclusion criteria and were included. RESULTS CEC is uncommon, accounting for 2%-10% of all esophageal carcinomas. These tumors are often locally advanced at presentation and have a poor prognosis, with a 5-year overall survival of 30%. Tobacco and alcohol consumption seem to be the major risk factors for developing CEC. Surgery is usually not possible due to the very close relationship to other organs such as the larynx, trachea and thyroid gland. Therefore, the current standard of care is definitive chemoradiation (dCRT) with curative intent. Treatment regimens used to treat CEC are adapted by established regimens in lower esophageal squamous cell carcinoma and head and neck squamous cell carcinoma. However, dCRT may be accompanied by severe side-effects and complications. Several diagnostic and predictive markers have been studied, but currently, there is no other biomarker than clinical stage to determine patient management. Suggestions to improve patient outcomes are to determine the exact radiation dose needed for adequate locoregional control and to combine radiotherapy with optimal systemic therapy backbone. CONCLUSION CEC remains unchartered territory for many practising physicians and patients with CEC have a poor prognosis. To improve the outcome for CEC patients, future studies should focus on the identification of new diagnostic biomarkers or targets for radiosensitizers, amelioration of radiation schedules, optimal combination of chemotherapeutic agents and/or new therapeutic targets.
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Affiliation(s)
- A Hoeben
- Department of Internal Medicine, Division of Medical Oncology
| | - J Polak
- Department of Internal Medicine, Division of Medical Oncology
| | | | - F Hoebers
- Department of Radiation Oncology (MAASTRO Clinic)
| | - H I Grabsch
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands Department of Pathology & Tumour Biology, Leeds Institute of Cancer Studies and Pathology, University of Leeds, Leeds, UK
| | - J de Vos-Geelen
- Department of Internal Medicine, Division of Medical Oncology
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Abstract
BACKGROUND Coincident thyroid and head and neck squamous cell carcinomas are rare. This paper presents a case of synchronous laryngeal squamous cell carcinoma, follicular thyroid carcinoma and micropapillary thyroid carcinoma. METHODS A PubMed search was performed for articles describing synchronous thyroid and head and neck squamous cell carcinomas, using the search terms 'thyroid cancer', 'cancer of the head and neck', 'synchronous' and 'synchronous neoplasm'. RESULTS The literature suggests that the head and neck squamous cell carcinoma stage is a better predictor of outcome than the extent of surgical treatment of the thyroid gland in synchronous malignancies. CONCLUSION The decision regarding surgical treatment of the thyroid in synchronous thyroid and head and neck squamous cell carcinomas should take several factors into account. The head and neck squamous cell carcinoma stage is the strongest predictor of outcome, although patient-related factors and the location of malignant thyroid tissue may also affect management.
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Shimizu M, Zaninotto G, Nagata K, Graham DY, Lauwers GY. Esophageal squamous cell carcinoma with special reference to its early stage. Best Pract Res Clin Gastroenterol 2013; 27:171-86. [PMID: 23809239 DOI: 10.1016/j.bpg.2013.03.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2012] [Accepted: 03/08/2013] [Indexed: 02/07/2023]
Abstract
The term 'early squamous cell carcinoma of the oesophagus', which was previously restricted to superficial carcinoma with no lymph node metastasis, now encompasses intramucosal carcinoma regardless of the nodal status. Such lesions are rare in Western countries, where the experience is limited. In recent years, the development and greater use of chromoendoscopy and narrow band imaging (NBI), both of which facilitate the evaluation of mucosal morphology, have played an important role in the detection of early esophageal squamous cell carcinoma. In addition, the techniques and indications of endoscopic resection (mucosal resection [EMR] and mucosal dissection [ESD]) are still being refined. In the present article, we will discuss the clinical and pathologic features of esophageal early squamous cell carcinoma, as well as the epidemiology and aetiology of esophageal cancer in general. In addition, we will provide a therapeutic decision tree taking into account endoscopic and surgical modalities as they apply to early esophageal squamous cell carcinoma.
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Affiliation(s)
- Michio Shimizu
- Department of Pathology, Saitama Medical University, Saitama International Medical Center, 1397-1 Yamane, Hidaka City, Saitama 350-1298, Japan.
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Yang Y, Tarapore RS, Jarmel MH, Tetreault MP, Katz JP. p53 mutation alters the effect of the esophageal tumor suppressor KLF5 on keratinocyte proliferation. Cell Cycle 2012; 11:4033-9. [PMID: 22990386 DOI: 10.4161/cc.22265] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Krüppel-like factor 5 (KLF5) is a key transcriptional regulator that is typically pro-proliferative in non-transformed epithelial cells but inhibits proliferation in transformed epithelial cells. However, the underlying mechanisms for this context-dependent function are not known. KLF5 is epigenetically silenced and exhibits a tumor suppressive function in esophageal squamous cell cancer (ESCC). Since p53 mutation is the most common genetic alteration in ESCC, as in other human epithelial cancers, we hypothesized that the context-dependent functions of KLF5 in cell proliferation were dependent on p53 status. In fact, in non-transformed human primary esophageal keratinocytes, when p53 was wild-type, KLF5 was pro-proliferative; however, KLF5 became anti-proliferative when p53 was mutated. KLF5 loss in human primary keratinocytes harboring p53 mutation accelerated the cell cycle and decreased expression of p21Waf1/Cip1; similar effects were also seen in ESCC cells with established p53 mutations. Further, p21Waf1/Cip1 was directly and differentially bound and regulated by KLF5 in the presence or absence of mutant p53, and suppression of p21Waf1/Cip1 reversed the antiproliferative effects of KLF5 in the presence of p53 mutation. Thus, KLF5 is a critical brake on an aberrant cell cycle, with important tumor suppressive functions in esophageal squamous cell and potentially other epithelial cancers.
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Affiliation(s)
- Yizeng Yang
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
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Abstract
The widely accepted paradigm for tumorigenesis begins with rate-limiting mutations in a key growth control gene resulting in immediate lesion growth. Tumor progression occurs as cells within the tumor acquire additional carcinogenic mutations. However, there is clear evidence that the road to cancer can begin long before the growth of a clinically detectable lesion - indeed, long before any of the usual morphological correlates of preneoplasia are recognizable. Field cancerization, the replacement of the normal cell population by a histologically nondysplastic but protumorigenic mutant cell clone, underlies the development of many cancer types, and in this article we review field cancerization in the GI tract. We present the evidence that field cancerization can underpin tumorigenesis in all gastrointestinal compartments, discuss the homeostatic mechanisms that could permit clone spread and highlight how an understanding of the mechanisms driving field cancerization is a means to study human stem cell biology. Finally, we discuss how appropriate recognition of the role of field cancerization in tumorigenesis could impact patient care.
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Affiliation(s)
- Trevor A Graham
- Histopathology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3LY, UK.
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19
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Shinoto M, Shioyama Y, Sasaki T, Nakamura K, Ohura H, Toh Y, Higaki Y, Yamaguchi T, Ohnishi K, Atsumi K, Hirata H, Honda H. Clinical Results of Definitive Chemoradiotherapy for Patients With Synchronous Head and Neck Squamous Cell Carcinoma and Esophageal Cancer. Am J Clin Oncol 2011; 34:362-6. [DOI: 10.1097/coc.0b013e3181e84b4b] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Peng J, Wang Y. Epidemiology, pathology and clinical management of multiple gastric cancers: a mini-review. Surg Oncol 2010; 19:e110-4. [PMID: 20566282 DOI: 10.1016/j.suronc.2010.05.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2010] [Revised: 04/09/2010] [Accepted: 05/31/2010] [Indexed: 02/07/2023]
Abstract
The incidence of multiple gastric cancers (MGCs) has been increasing over the recent decades due to the advance in diagnostic techniques combining with the detailed pathological examinations of surgical resection specimens. Reduction of the surgical extent and trauma under the premise of radical resection improves the quality of life of patients with gastric cancer. However, MGC lesions may have been missed, which can result in adverse consequences. We carried out this systematic review of previous literatures, in order to provide deep insights into epidemiological, pathological and clinical features of MGCs and to establish an efficient way to screen the individuals with high risks. MGCs represent a special type of malignant gastric tumor and possess distinctive features compared with the solitary one. More attention should be paid to both diagnosis and treatment of MGCs. Possibility of overlooking accessory lesions must be kept in mind constantly. For the population at high risk, such as the elderly with differentiated type, strict perioperative tissue examinations and follow-up are essential.
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Affiliation(s)
- Jiayuan Peng
- The Department of Surgery, The Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China
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21
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Does daily alcohol and/or cigarette consumption cause low-grade dysplasia, a precursor of esophageal squamous cell carcinoma? J Clin Gastroenterol 2010; 44:173-9. [PMID: 19826274 DOI: 10.1097/mcg.0b013e3181bb837a] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Cigarette smoking and alcohol consumption are well-known risk factors for esophageal squamous cell carcinoma (ESCC), which has a very poor prognosis. Successful screening strategies for precursor lesions that can be targets for early detection and treatment are required to prevent ESCC. METHODS This is a prospectively cross-sectional study. To clarify whether daily smoking and/or alcohol consumption are risk factors for dysplasia, which is the initial lesion leading to ESCC. Lugol chromoendoscopy was performed in 1,345 eligible individuals. Six hundred ninety individuals had daily smoking and/or alcohol consumption; 655 individuals did not smoke and drink alcohol. The effects of smoking and alcohol consumption among high-grade dysplasia (HGD), low-grade dysplasia (LGD), and controls without dysplasia were evaluated using multiple logistic regression analysis. RESULTS Among 1,345 individuals, 17 HGD and 23 LGD lesions were confirmed histologically. The prevalence of both smoking and drinking consumption was significantly higher in HGD than in LGD individuals (age and sex adjusted odds ratio; 113.0, 95% confidence interval; 6.26), whereas no significant difference was seen in both consumption between LGD individuals and controls (odds ratio; 1.29, 95% confidence interval; 0.33-6.37). Approximately 70% of HGD individuals, but only 13% of LGD individuals, both smoked and consumed alcohol. CONCLUSIONS Daily cigarette and alcohol consumption were not the risk factors for LGD, however, consumption of both were high-risk factors for HGD. We suggest that documenting the difference of risk factors for LGD and HGD can assist in the development of effective screening, early detection, and prevention strategies for ESCC.
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Abstract
Carcinoma of the oesophagus including carcinoma of gastro-oesophageal junction are rapidly increasing in incidence. During recent years there have been changes in the knowledge surrounding biology of the disease progression. Identification of dysplasia in mucosal biopsies is the most reliable pathologic indicator of an increased risk of development of squamous cell carcinoma and passes through the sequence of chronic esophagitis, low-grade and high-grade dysplasia and invasive carcinoma. Although Barrett's esophagus is a precursor to esophageal adenocarcinoma and have a well described sequence of carcinogenesis: the Barrett's metaplasia-dysplasia-adenocarcinoma sequence, not all patients with this disorder require intensive surveillance. The natural history of dysplasia is poorly understood, particularly in low-risk regions, and prospective follow-up studies are needed. Adjunctive methods to improve reproducibility, such as immunostaining for alpha-methylacyl-coenzyme A racemase (AMACR), show promise, but require confirmation in larger studies. In addition, several controversial methods such as detection of p16, p53, and DNA content abnormalities may help identify patients at particularly high risk for progression to cancer, but these techniques are not yet widely available for routine clinical application. More studies are needed to define other early nonmorphologic biomarkers for risk of squamous cell carcinoma. Recent evidence regarding the importance of several histopathologically derived prognostic factors, such as circumferential resection margin status and lymph node metastases are evaluated, including lymph node micrometastases and the sentinel node concept. With the rising use of multimodal treatments for oesophageal cancer it is important that the response of the tumour to this therapy can be carefully documented by histopathology.
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Shimizu M, Nagata K, Yamaguchi H, Kita H. Squamous intraepithelial neoplasia of the esophagus: past, present, and future. J Gastroenterol 2009; 44:103-12. [PMID: 19214671 DOI: 10.1007/s00535-008-2298-y] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2008] [Accepted: 09/05/2008] [Indexed: 02/04/2023]
Abstract
With regard to the esophagus, the term "squamous dysplasia" has been used in European countries, the United States, and China, while its use is controversial in Japan. Recently, "low-grade intraepithelial neoplasia" and "high-grade intraepithelial neoplasia" have been used as inclusive terms for dysplasia and carcinoma in situ in the World Health Organization classification. Endoscopically, it is often difficult to identify squamous intraepithelial neoplasia by conventional endoscopy, but application of iodine is useful for the diagnosis of such a lesion. In addition, new types of endoscopic techniques, including magnifying endoscopy, narrow-band imaging (NBI), and endocytoscopy are helpful to detect squamous intraepithelial neoplasia. NBI is very useful for identifying the intrapapillary capillary loop pattern. Regarding the pathological criteria of squamous dysplasia and squamous cell carcinoma, the views of Japanese and Western pathologists have differed significantly. Before the term "intraepithelial neoplasia" was introduced, severe dysplasia as diagnosed by Western pathologists was in fact the same as squamous cell carcinoma in situ or noninvasive carcinoma as diagnosed by Japanese pathologists. This problem has been solved by the introduction of the Vienna classification; however, there are still some issues that need to be resolved. One of them is the presence of basal layer type squamous cell carcinoma in situ, which is often underdiagnosed as lowgrade intraepithelial neoplasia by Western pathologists. Endoscopic treatments such as endoscopic mucosal resection and endoscopic submucosal dissection have recently become possible choices for squamous intraepithelial neoplasia; however, these techniques are not in widespread use in the West. We believe that a consensus meeting between Japanese and Western pathologists as well as endoscopists should be held promptly to reach a common ground for the nomenclature.
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Affiliation(s)
- Michio Shimizu
- Department of Pathology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka 350-1298, Japan
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Multifocal neoplasia and nodal metastases in T1 esophageal carcinoma: implications for endoscopic treatment. Ann Surg 2008; 247:434-9. [PMID: 18376186 DOI: 10.1097/sla.0b013e318163a2ff] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE There has been an increase in interest in endoscopic therapy (ET) for intramucosal (T1a) or submucosal (T1b) esophageal carcinoma. The objective of the present study was to determine the prevalence of nodal metastases, lymphatic vascular invasion, and multifocal neoplasia in patients with pT1 esophageal carcinoma who underwent esophagectomy without preoperative therapy and assess their potential implication for ET. METHODS We retrospectively reviewed the records of all patients who underwent esophagectomy without preoperative therapy for pT1 esophageal cancer. A detailed review of all pathology reports was performed to identify relevant pathologic criteria including depth of invasion (T1a or T1b), cell type (adenocarcinoma/squamous), tumor differentiation (poor vs. well/moderate), extent of Barrett esophagus (short segment [SSBE] and long segment [LSBE]), nodal status, lymphovascular invasion (LVI), and the presence of multifocal neoplasia (MFN) (high-grade dysplasia or invasive carcinoma). Overall survival and disease-specific survival were determined by the Kaplan-Meier method. RESULTS There were 75 consecutive patients (58 men, 17 women) between January 1994 and September 2006. Median age was 68 years. Hospital mortality was 2.6% (2 of 75). Thirty patients had T1a and 45 had T1b. Sixty patients had adenocarcinoma. Nodal metastases were present in 2 of 30 (6%) T1a and 8 of 45 (17.5%) T1b tumors. MFN was present in 30% (9 of 30) of T1a tumors and 29% (13 of 45) of T1b tumors. All 9 patients with LVI had T1b tumors. Collectively, 10 of 30 (33.3%) patients with T1a and 25 of 45 (58%) with T1b had MFN, LVI, or nodal metastases. Forty-nine patients had adenocarcinoma with associated BE (23 SSBE, 26 LSBE). There was no difference between patients with SSBE and those with LSBE in the incidence of nodal disease (2 of 23 vs. 2 of 26) but a significant difference in the incidence of MFN (3 of 23 vs. 13 of 26, P = 0.006). Four patients with squamous carcinoma had nodal metastases and 5 had MFN. Overall 5-year survival was 78% (T1a:90% T1b: 71%, P = 0.07). Five-year disease-specific survival was 86.5% (T1a: 96.7%, T1b: 79.6%, P = 0.06). CONCLUSION The combined high incidence of MFN, LVI, and occult nodal metastases does not support the use of ET in patients with T1 esophageal cancer regardless of depth of invasion, cell type, differentiation or extent of BE. ET may be of value in patients in whom surgical risk is considered prohibitive.
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Bahnassy AA, Zekri ARN, Abdallah S, El-Shehaby AMR, Sherif GM. Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival. Pathol Int 2005; 55:53-62. [PMID: 15693850 DOI: 10.1111/j.1440-1827.2005.01804.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf). Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are independent prognostic markers.
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Affiliation(s)
- Abeer A Bahnassy
- Department of Pathology, National Cancer Institute, Kaser El-Aini School of Medicine, Cairo University, Fom El-Khalig, Cairo 11796, Egypt
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Natsugoe S, Matsumoto M, Okumura H, Ishigami S, Uenosono Y, Owaki T, Takao S, Aikou T. Multiple primary carcinomas with esophageal squamous cell cancer: clinicopathologic outcome. World J Surg 2005; 29:46-9. [PMID: 15592914 DOI: 10.1007/s00268-004-7525-y] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The incidence of multiple primary carcinomas (MPCs) associated with esophageal cancer has increased. The purpose of this study was to analyze clinicopathologic findings for MPC and for only esophageal cancer (OEC). Of 157 patients with MPCs, 60 had synchronous cancer and 97 metachronous cancer. Another 42 patients had antecedent esophageal cancer (AEC), and 55 patients had subsequent esophageal cancer (SEC). We retrospectively analyzed the clincopathologic findings for patients in these categories. The incidence of early-stage carcinoma was higher in patients with MPCs than in those with an OEC. Of patients with MPCs, those with metachronous cancer had a higher rate of early-stage carcinoma than those with synchronous cancer. The 5-year survival rates were not significantly different for MPC and OEC patients. Patients with metachronous cancer had a significantly better prognosis than those with synchronous cancer (p = 0.017); and in the metachronous cancer group the prognosis was significantly better for patients with AEC than for those with SEC (p = 0.0005). Meticulous follow-up after treatment of a first cancer should be required to detect other early-stage carcinomas.
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Affiliation(s)
- Shoji Natsugoe
- Department of Surgical Oncology and Digestive Surgery, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, 890-8520 Kagoshima, Japan.
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Yamamoto S, Tomita Y, Hoshida Y, Iizuka N, Kidogami S, Miyata H, Takiguchi S, Fujiwara Y, Yasuda T, Yano M, Nakamori S, Sakon M, Monden M, Aozasa K. Expression level of valosin-containing protein (p97) is associated with prognosis of esophageal carcinoma. Clin Cancer Res 2005; 10:5558-65. [PMID: 15328197 DOI: 10.1158/1078-0432.ccr-0723-03] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE Esophageal squamous cell carcinoma (ESCC) frequently shows a poor prognosis because of the occurrence of systemic metastasis, mainly via lymphatic vessels. Valosin-containing protein (VCP) has been shown to be associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. In the present study, we examined the association of VCP with the recurrence and prognosis of ESCC. EXPERIMENTAL DESIGN VCP expression in 156 ESCC patients [139 males and 17 females; age range, 38-82 (median, 60) years] was analyzed by immunohistochemistry. Staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. The correlation of VCP expression between the mRNA and protein levels was examined in 12 patients. RESULTS Fifty-seven (37.3%) cases showed level 1 and 96 (62.7%) level 2 VCP expression. Quantitative reverse transcription-PCR analysis revealed greater VCP mRNA expression in level 2 (n = 6) than level 1 cases (n = 6; P < 0.05). ESCC with level 2 expression showed higher rates of lymph node metastasis (P < 0.01) and deep tumor invasion (P < 0.01), and poorer disease-free and overall survival rates (P < 0.001 for both analyses) than ESCC with level 1 expression. Multivariate analysis revealed that VCP expression level is an independent prognosticator for disease-free and overall survival. Furthermore, VCP level was an indicator for disease-free survival in the early (pT1) and the advanced (pT2-pT4) stage groups. CONCLUSION This study demonstrated the prognostic significance of VCP expression in ESCC.
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Affiliation(s)
- Shinji Yamamoto
- Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, Osaka, Japan
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Ito S, Ohga T, Saeki H, Nakamura T, Watanabe M, Tanaka S, Kakeji Y, Maehara Y. p53 mutation profiling of multiple esophageal carcinoma using laser capture microdissection to demonstrate field carcinogenesis. Int J Cancer 2005; 113:22-28. [PMID: 15386362 DOI: 10.1002/ijc.20500] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Inactivation of the p53 tumor suppressor gene is one of the most frequent genetic alterations observed in human esophageal carcinomas. In patients with esophageal carcinoma, one of the significant pathological features of the tumor is the presence of multiple lesions within the esophagus. However, the molecular mechanisms involved in the occurrence of multiple lesions have remained elusive. To characterize p53 alterations in multiple esophageal carcinomas and to study their roles in carcinogenesis, we performed p53 immunohistochemical and p53 mutation analyses using laser capture microdissection on surgically resected human esophageal carcinomas from 11 patients: 9 patients with multiple esophageal carcinomas, 1 with an intramural metastasis lesion within the esophagus and 1 with an intraepithelial carcinoma lesion contiguous to the main lesion. In each of the patients with multiple esophageal carcinomas, we examined samples from 1 main lesion and 1 representative concomitant lesion. Molecular analyses of samples from fresh-frozen normal tissues and tumor tissues of the main lesion (whole tumor) were also performed by the same method. p53 protein accumulation was observed in 16 (72.7%) of 22 lesions from the 11 cases. No p53 mutation was found in normal esophageal tissues. In the 9 cases of multiple esophageal carcinomas, point mutations were detected in the whole tumor in 1 (11.1%) case, in the microdissected tumor samples of main lesions in 3 (33.3%) cases and in the microdissected tumor samples of concomitant lesions in 3 (33.3%) cases. For the microdissected tumor samples, there was a 54.5% (12/22) concordance rate between the results of immunostaining and molecular analysis. In the 8 cases of whole tumors in which a p53 mutation was not observed, 2 cases revealed p53 mutation in the microdissected tumor samples of the main lesion. All 6 cases of multiple esophageal carcinomas that showed a p53 mutation in the microdissected tumor sample had a discordant p53 mutational status between the main and concomitant lesions. In contrast, both the intramural metastasis lesion and the intraepithelial carcinoma contiguous to the main lesion showed p53 mutational patterns identical to those of the main lesions. In conclusion, the analysis of microdissected DNA by laser capture microdissection is useful for characterizing the heterogeneity of the p53 gene mutation in multiple carcinoma lesions that cannot be accurately analyzed in whole esophageal tumor DNA. The finding of different p53 gene mutations among multiple esophageal carcinoma lesions suggest further evidence of multicentric or field carcinogenesis of the human esophagus.
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Affiliation(s)
- Shuhei Ito
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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Zuo LF, Lin PZ, Qi FY, Guo JW, Liu JH. Flow cytometric analysis of DNA, telomerase content and multi-gene expression in esophageal epithelial dysplasia. World J Gastroenterol 2003; 9:2409-12. [PMID: 14606066 PMCID: PMC4656511 DOI: 10.3748/wjg.v9.i11.2409] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the alteration of molecular events and the early carcinogenesis mechanism of esophageal epithelial cells in the high incidence area of esophageal cancer.
METHODS: Esophageal epithelial cells of esophageal cancer patients were collected from the high incidence area in China. Content of DNA and telomerase as well as multi-gene expressions such as p53, p21 and cyclin D1 in esophageal precancer cells were quantitatively analysed by flow cytometry (FCM) with indirect immunofluorescence technique and DNA propidium iodide fluorescence staining.
RESULTS: FCM analysis results showed the DNA content increased significantly and the heteroploid rate was 87.9% in occurred carcinogenesis. P53 protein accumulation and ras p21 increase were seen in the early carcinogenesis of the esophagus. The positive rate of p53 and ras p21 was 100% (5/5, 4/4 respectively) in the cancer group. Telomerase and oncogene cyclin D1 were over- expressed in all of the cancer patients.
CONCLUSION: Increased DNA content and heteroploid rate, accumulation of p53 protein, and over-expression of p21, telomerase and cyclin D1 proteins were early molecular events during the development of esophageal cancer.
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Affiliation(s)
- Lian-Fu Zuo
- Hebei Provincial Tumor Institute, Shijiazhuang 050011, Hebei Province, China.
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Masuda N, Kato H, Nakajima T, Sano T, Kashiwabara K, Oyama T, Kuwano H. Synergistic decline in expressions of p73 and p21 with invasion in esophageal cancers. Cancer Sci 2003; 94:612-7. [PMID: 12841870 PMCID: PMC11160286 DOI: 10.1111/j.1349-7006.2003.tb01491.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] [Received: 02/05/2003] [Revised: 05/08/2003] [Accepted: 05/19/2003] [Indexed: 11/27/2022] Open
Abstract
The significance of the p73 gene, a homologue of the p53 gene, in esophageal cancers is not fully understood. In order to clarify the role of p73 expression in esophageal cancers, p73 expression was immunohistochemically investigated in 106 surgically resected esophageal cancers and the results were compared with various clinicopathological factors. In normal esophageal epithelium, the expression of p73 was observed only in the nuclei of basal cells. In esophageal cancers, p73 immunoreactivity was observed in all intraepithelial lesions except one cancer, and was reduced with cancer invasion, to 78% and 64% at superficial invasion and deep invasion sites, respectively. However, p73 expression was not correlated with any other clinicopathological factor. The expressions of p53 and p21 were also investigated in esophageal cancer. To evaluate the status of the p53 gene mutation immunohistochemically, two monoclonal antibodies (DO7 and PAb240) were used. There seemed to be an inverse correlation between p73 expression and p53 mutation. Moreover, the expression of p21 was highly correlated with p73 expression irrespective of the p53 mutation status. In human esophageal cancers, p73 expression decreased with increasing degree of tumor invasion, and its decreased expression in local advanced tumor caused down-regulation of p21 expression, which might reflect tumor progression.
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Affiliation(s)
- Norihiro Masuda
- First Department of Surgery and Second Department of Pathology, Gunma University School of Medicine, Maebashi 371-8551, Japan.
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Okazaki Y, Tanaka Y, Tonogi M, Yamane G. Investigation of environmental factors for diagnosing malignant potential in oral epithelial dysplasia. Oral Oncol 2002; 38:562-73. [PMID: 12167434 DOI: 10.1016/s1368-8375(01)00119-1] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
A study was conducted in rats with early tongue carcinoma induced by 4-nitroquinoline 1-oxide (4NQO), in order to investigate the early diagnosis of malignant potential of epithelial dysplasia. The rat tongue lesions were classified by their severity into three groups corresponding to early cancer, dysplasia and no change. The grade of epithelial changes was determined according to 13 items of WHO Epithelial Dysplasia Criteria. The expression levels of p53 and Bcl-2 proteins were detected immunohistochemically, and apoptotic cells were detected using the TUNEL method. In addition, a p53 mutation by lesions was detected. The expression ratio of p53 protein was high in dysplasia, and the ratio of Bcl-2 protein was high in early cancer and dysplasia. The TUNEL-positive cells were observed primarily in the granular layers of the no change cells, and their numbers decreased as the cells shifted to the early cancer stage. The p53 mutation was detected using a microdissection method in dysplasia, where it was found in three out of nine lesions. All the mutations in dysplasia detected were on the same codon that was found to be mutated in the early cancer. These results indicate that the association between the p53 mutation and histological changes in carcinogenesis epithelial dysplasia is strong, and that both the identification of p53- and Bcl-2-positive epithelium, and decrease in the TUNEL positive ratio, were useful for the diagnosis of the malignant potential of precancerous lesions.
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Affiliation(s)
- Y Okazaki
- Department of Oral Medicine, Tokyo Dental College 5-11-13 Sugano, Chiba 272-8513, Ichikawa City, Japan.
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Saeki H, Kimura Y, Ito S, Miyazaki M, Ohga T. Biologic and clinical significance of squamous epithelial dysplasia of the esophagus. Surgery 2002; 131:S22-7. [PMID: 11821783 DOI: 10.1067/msy.2002.119290] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Squamous epithelial dysplasia is frequently encountered in the cancerous esophagus. However, its biological and clinical significance have not yet been fully elucidated. Investigations in squamous cell dysplasia of the esophagus have been performed to date in our department. We consider dysplasia to be the earliest malignancy of the esophagus based on such biologic features as the histopathologic findings, the proliferative activity, and the altered expression of cancer-associated genes. It is essential to detect and treat these early lesions endoscopically. Hopefully the findings of further studies of dysplasia can help to elucidate the mechanism of carcinogenesis in esophageal squamous cell carcinoma.
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Affiliation(s)
- Hiroshi Saeki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
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