• Humans
• Leukoplakia, Oral/genetics
• Leukoplakia, Oral/pathology
• Cell Transformation, Neoplastic/genetics
• Cell Transformation, Neoplastic/pathology
• Aneuploidy
• Ploidies
• Mouth Neoplasms/genetics
• Mouth Neoplasms/pathology

• DNA ploidy
• Oral squamous cell carcinoma
• Recurrence
• S phase fraction
• Second primary tumor
• Wide field of cancerization

• Humans
• Mouth Neoplasms/genetics
• Mouth Neoplasms/pathology
• Male
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/pathology
• Female
• Middle Aged
• Neoplasm Recurrence, Local
• Prospective Studies
• Ploidies
• Sudan
• Adult
• Longitudinal Studies
• Aged
• Lymphatic Metastasis/pathology
• Neoplasms, Second Primary/genetics
• Neoplasms, Second Primary/pathology
• S Phase/genetics
• Follow-Up Studies
• Prognosis
• Flow Cytometry
• Aneuploidy
• DNA, Neoplasm/analysis
• Neoplasm Staging
• Aged, 80 and over

• aneuploidy
• dysplasia
• oral cytology
• oral squamous cell carcinoma
• prognosis

• Adult
• Aged
• Aged, 80 and over
• Female
• Humans
• Male
• Middle Aged
• Algorithms
• Cytodiagnosis/methods
• Disease Progression
• Early Detection of Cancer
• Mouth Neoplasms/pathology
• Mouth Neoplasms/genetics
• Ploidies
• Precancerous Conditions/pathology
• Precancerous Conditions/genetics
• Prognosis
• Retrospective Studies
• Sensitivity and Specificity

• 23490 Mitacs Accelerate
• 2021 (707062) Canadian Cancer Society Research Institute
• I2C02020-0727 Michael Smith Health Research BC

• DNA ploidy
• malignant transformation
• mouth neoplasms
• oral leukoplakia
• proliferative verrucous leukoplakia

• Humans
• Mouth Neoplasms/genetics
• Mouth Neoplasms/pathology
• Prospective Studies
• Leukoplakia, Oral/genetics
• Leukoplakia, Oral/pathology
• Ploidies
• Cell Transformation, Neoplastic/genetics
• Cell Transformation, Neoplastic/pathology
• DNA

• Bio-marker
• DNA ploidy
• OPMD
• brush biopsy
• image cytometry
• malignancy

• DNA ploidy
• leukoplakia
• loss of heterozygosity
• oral cancer
• oral potentially malignant disorder
• premalignancy

• DNA ploidy
• dysplasia
• leukoplakia
• malignant
• oral potentially malignant disorder

• DNA ploidy
• copy number alteration
• loss of heterozygosity (LOH)
• oral dysplasia
• oral potentially malignant disorder

Methods to analyze progression of carcinogenesis and stage of cancer are vital nowadays due to the high prevalence of these lesions. DNA ploidy analysis is one such important method in early diagnosis and improving prognosis.

The aim of this study was to correlate histopathological grading and DNA ploidy in oral leukoplakia, oral submucous fibrosis (OSMF), and oral squamous cell carcinoma (OSCC) cases.

Our study included 80 subjects, grouped into 4 groups of 20 each of OSCC, leukoplakia, OSMF, and healthy individuals. Histopathological grading was carried out in study cases, DNA ploidy was estimated using flow cytometry, and both the findings were correlated.

Among the 20 cases of leukoplakia group, 6 cases showed aneuploidy and 14 showed diploidy. In the 20 cases of OSF group, 2 cases showed aneuploidy and 18 showed diploidy, and in the 20 cases of OSCC group, 10 showed aneuploidy and 10 showed diploidy. Most of the aneuploidy cases showed severe dysplasia.

Analysis of DNA ploidy status can serve as a diagnostic tool for early detection of malignancies owing to the subjective nature of traditional histopathological grading.

• Aneuploid
• DNA ploidy
• diploid
• flow cytometry
• leukoplakia
• oral cancer

• Fanconi anemia
• cytology
• early detection of cancer
• image cytometry
• oral cancer
• sensitivity
• squamous intraepithelial lesions

• Aneuploid
• DNA repair Capacity
• Diploid
• Telomerase
• leukoplakia

Subjectivity in oral dysplasia grading has prompted evaluation of molecular-based tests to predict malignant transformation. Aneuploidy detected by DNA image-based cytometry (ICM) is currently the best predictor but fails to detect certain high risk lesions. A novel multiplex fluorescence in situ hybridization (FISH) panel was used to explore possible explanations by detecting aneuploidy at the single cell level. FISH was compared to reference standard DNA ICM in 19 oral lesions with epithelial dysplasia and used to characterize the cellular architecture. Copy number variation at 3q28, 7p11.2, 8q24.3, 11q13.3 and 20q13.12 and matched chromosome specific loci were assessed by dual-color FISH to assess numerical and spatial patterns of copy number increase and gene amplification. FISH revealed wide variation in copy number at different loci. Only low level copy number gain was present and often in only a small proportion of cells, although usually with all or all but one locus (9/12). Four cases showed gene amplification, one at two loci. Some probes revealed an internal presumed clonal structure within lesions not apparent in routine histological examination. Both methods produced similar diagnostic results with concordance in detection of aneuploidy by both methods in 17 out of 19 samples (89%). We have shown that oral dysplastic lesions may contain very few aneuploid cells at a cellular level, high copy number gain is rare and changes appear to arise from large chromosomal fragment duplications. Single stem lines are relatively homogeneous for loci with copy number gain but there is a subclonal structure revealed by gene amplification in some lesions.

• Cytology
• PMODs
• Ploidy

• Diagnosis
• Non-invasive
• Optical imaging
• Oral cancer

The value of image cytometry DNA ploidy analysis and dysplasia grading to predict malignant transformation has been determined in oral lesions considered to be at ‘high’ risk on the basis of clinical information and biopsy result. 10-year follow up data for 259 sequential patients with oral lesions clinically at ‘high’ risk of malignant transformation were matched to cancer registry and local pathology database records of malignant outcomes, ploidy result and histological dysplasia grade. In multivariate analysis (n = 228 patients), 24 developed carcinoma and of these, 14 prior biopsy samples were aneuploid. Aneuploidy was a significant predictor (hazard ratio 7.92; 95% CI 3.45, 18.17) compared with diploidy (p < 0.001). The positive predictive value (PPV) for severe dysplasia was 50% (95% CI 31.5, 68.5) and for aneuploid lesions, 33.3% (95% CI 19.0, 47.6). Combined DNA aneuploidy and severe dysplasia increased PPV to 56.3% (95% CI 31.9, 80.6). Diploid-tetraploid and non-dysplastic status had high negative predictive values (NPV) of 94.6% (95% CI 91.4, 97.8) and 99.17% (95% CI 97.4, 100.8) respectively. DNA ploidy predicts malignant transformation well and combining it with dysplasia grading gave the highest predictive value. The predictive values reported here exceed those from other investigations to date.

• aneuploidy
• diploidy
• malignant transformation
• meta-analysis

• AgNORs
• Ameloblastic carcinoma
• Ameloblastoma
• Clear cell odontogenic carcinoma
• Flow cytometry
• Keratocystic odontogenic tumor

Cells are open, highly ordered systems that are far away from equilibrium. For this reason, the first function of any cell is to prevent the permanent threat of disintegration that is described by thermodynamic laws and to preserve highly ordered cell characteristics such as structures, the cell cycle, or metabolism. In this context, three basic categories play a central role: energy, information, and matter. Each of these three categories is equally important to the cell and they are reciprocally dependent. We therefore suggest that energy loss (e.g., through impaired mitochondria) or disturbance of information (e.g., through mutations or aneuploidy) or changes in the composition or distribution of matter (e.g., through micro-environmental changes or toxic agents) can irreversibly disturb molecular mechanisms, leading to increased local entropy of cellular functions and structures. In terms of physics, changes to these normally highly ordered reaction probabilities lead to a state that is irreversibly biologically imbalanced, but that is thermodynamically more stable. This primary change—independent of the initiator—now provokes and drives a complex interplay between the availability of energy, the composition, and distribution of matter and increasing information disturbance that is dependent upon reactions that try to overcome or stabilize this intracellular, irreversible disorder described by entropy. Because a return to the original ordered state is not possible for thermodynamic reasons, the cells either die or else they persist in a metastable state. In the latter case, they enter into a self-driven adaptive and evolutionary process that generates a progression of disordered cells and that results in a broad spectrum of progeny with different characteristics. Possibly, 1 day, one of these cells will show an autonomous and aggressive behavior—it will be a cancer cell.

• aneuploidy
• cancer
• carcinogenesis
• entropy
• matter
• microenvironment
• mutations
• warburg effect

Oral cancer is the sixth most common malignancy with almost 500000 new cases reported worldwide annually. The diagnosis of oral cancer at an early stage has a good prognosis as the survival rate is high (around 80%). However, the majority of oral cancer cases are diagnosed at a later stage with a considerably poor 5-year survival rate of 50% according to World Health Organization statistics. Thus, an effective management strategy for oral cancer will depend on its early identification and intervention which would pave the way for superior prognosis. Despite the obvious advantage of earlier diagnosis of oral cancer, no approach has yet proven to be a reliably successful in diagnosis of oral cancer at an early stage. Currently; the primary line of screening of oral cancer is performed by visual inspection, which is a subjective examination. Among the screening tests or diagnostic aids now available for oral cancer, few (toluidine blue, brush biopsy, salivary and serum bio-markers) have been utilised and studied for many years while others have recently become commercially available. The authors in the present article review all the modalities of screening aids used in oral cancer detection and provide an update on the latest screening tools used in oral cancer detection.

• Oral cancer
• Diagnostic aids
• Brush biopsy
• Tissue fluorescence

Oral epithelial dysplasia (OED) and carcinoma in situ (CIS) are defined by dysplastic cells in the epithelium. Over a third of oral squamous cell carcinoma (OSCC) patients present with associated OED. However, accurate histopathological diagnosis of such lesions is difficult. Nucleus accumbens-associated protein 1 (NAC1) is a member of the Pox virus and Zinc finger/Bric-a-brac Tramtrack Broad complex family of proteins, and is overexpressed in OSCC. This study aimed to determine whether NAC1 has the potential to be used as a marker to distinguish OED and OSCC.

The study included 114 patients (64 men, 50 women). There were 67, 10, and 37 patients with OED, CIS, and OSCC, respectively. NAC1 labeling indices (LIs) and immunoreactivity intensities (IRI) were evaluated. The patients’ pathological classification was significantly associated with age, sex, NAC1 LIs, and NAC1 IRI (p = 0.025, p = 0.022, p < 0.001, and p < 0.001, respectively). As a result of multivariate analysis, a predictive model was made; this identified the NAC1 LIs (OR [95% CI] 1.18 [1.11–1.28], p < 0.001) and NAC1 IRI (0.78 [0.68–0.86], p < 0.001) as predictive factors for CIS/OSCC. The NAC1 LIs/IRI cut-off values which discriminated between OED and CIS/OSCC were 50%/124 pixels. For NAC1 LIs with > 50% positivity the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.766, 0.910, 0.857, and 0.847, respectively. For NAC1 IRI with ≤ 124 positive pixels, the sensitivity, specificity, PPV, and NPV were 0.787, 0.866, 0.804, and 0.853, respectively. Though there are several potential limitations to this study and the results were obtained from a retrospective analysis of a single site cohort, the data suggest that the NAC1 LIs/IRI is a strong predictor of CIS/OSCC.

NAC1 has potential as a marker for distinguishing OED from CIS/OSCC.

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/metabolism
• Carcinoma, Squamous Cell/diagnosis
• Carcinoma, Squamous Cell/metabolism
• Diagnosis, Differential
• Epithelium/metabolism
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Middle Aged
• Mouth Neoplasms/diagnosis
• Mouth Neoplasms/metabolism
• Neoplasm Proteins/metabolism
• Repressor Proteins/metabolism
• Retrospective Studies