Classificatory updates in verrucous and cuniculatum carcinomas:Insights from the 5^(th) edition of WHO-IARC head and neck tumor classification

The International Agency for Research on Cancer(IARC)and World Health Organization(WHO)collaboratively produce the'WHO Blue Books'essential tools standardizing the diagnostic process for human cancers.Regular updates in this classification accommodate emerging molecular discoveries,advances in immunohistochemical techniques,and evolving clinical insights.The 5th edition of the WHO/IARC classification of head and neck tumors refines the'Oral Cavity and Mobile Tongue'chapter,including sections for non-neoplastic lesions,epithelial tumors,and tumors of uncertain histogenesis.Notably,the epithelial tumors section is rearranged by tumor behavior,starting with benign squamous papillomas and progressing through potentially malignant oral disorders to oral squamous cell carcinoma(OSCC).The section on OSCC reflects recent information on epidemiology,pathogenesis,and histological prognostic factors.Noteworthy is the specific categorization of verrucous carcinoma(VC)and carcinoma cuniculatum(CC),both associated with the oral cavity and distinct in clinical and histologic characteristics.This classification adjustment emphasizes the oral cavity as their predominant site in the head and neck.Designating specific sections for VC and CC aims to provide comprehensive insights into these unique subtypes,elucidating their clinical features,distinct histological characteristics,prevalence,significance,and clinical relevance.By categorizing these subtypes into specific sections,the 5th edition of the WHO classification aims to provide a more nuanced and detailed account,enhancing our understanding of these specific variants within the broader spectrum of head and neck tumors.

Expression of Angiopoietin-2 and Vascular Endothelial Growth Factor in Oral Squamous Cell Carcinoma and Its Significance

Objective： To investigate the expression of angiopoietin-2 （Ang-2） and vascular endothelialcell growth factor （VEGF） in oral squamous cell carcinoma （OSCC） and their correlations with clinicopathologic parameters, angiogenesis and vessel maturation of OSCC. Methods： The expression of Ang-2 and VEGF was detected in 41 speciments of human OSCC, 30 adjacent noncancerous oral tissues and 10 specimens of normal oral mucosa by conventional immumohistochemistry. Microvessel density （MVD） and vessel maturation index （VMI） were also assessed by double-labelling immumohistochemistry staining against CD34, a marker of pan-endothelial cells, and that against alpha-smooth muscle actin （α-SMA）, a marker of mural cells （pericytes/smooth muscle cells）. Results： The positive expression rate of Ang-2 and VEGF in 41 OSCC tissues was 51.22% and 63.42%, respectively. The expression of Ang-2 and VEGF was significantly higher in OSCC than in adjacent noncancerous oral tissues （all P〈0.05） and normal oral mucosa （all P〈0.05）. In the clinicopathologic parameters, the Ang-2 expression was closely correlated with tumor lymph node metastasis （P〈0.01） and the VEGF expression was correlated with tumor differentiated degree （P〈0.05）, but there was no significant correlation among the Ang-2 and VEGF expression and patients＇ sex, age and TNM stages （all P〉0.05）. The MVD of OSCC positive for both Ang-2 and VEGF was significantly higher than that of OSCC negative for both Ang-2 and VEGF （P〈0.05）. The VMI of OSCC positive for Ang-2 was significantly lower than that of OSCC negative for Ang-2 （P〈0.05）. When Ang-2 expression was combined with the staus of VEGF expression, MVD of OSCC positive for both Ang-2 and VEGF was the highest （51.08±2.99） as compared with that of other status in patient with OSCC （all P〈0.05）. Conclusion： The overexpression of Ang-2 and VEGF may play a crucial role in the development of OSCC. They are closely associated with angiogenesis and vessel maturation of tumor.

CORRELATIONS AMONG EXPRESSION OF ANGIOPOIETIN-1 TO CLINICAL PATHOLOGICAL CHARACTERISTICS AN ANGIO-GENESIS IN ORAL SQUAMOUS CELL CARCINOMA

Objective： To study the expression and the significance of Angiopoietin-1 （Ang-1） through observing the correlations among the expression of Ang-1 to clinicopathologic characteristics and microvessel density （MVD） in oral squamous cell carcinoma （OSCC）. Methods： Expressions of Angiopoietin-1 and CD34 in 41 human OSCC tissues, 30 adjacent noncancerous oral tissues and 10 normal oral mucosas were detected by immunohistochemical SABC method. MCD was also assessed. Results： Of the 41 OSCC tissues, 41.46% （17/41） was Ang-1 positive. The expression of Ang-1 was significantly lower in OSCC than that in adjacent noncancerous oral tissues （P〈0.05） and normal oral mucosa （P〈0.05）. The Ang-1 expression was significantly higher in high differentiated tumor than that in moderately differentiated tumor （P〈0.05）. The MVD was significantly higher in Ang-1-negative OSCC than in Ang-1-positive OSCC （P〈0.01）, and negatively correlated with the expression of Ang-1 （r=-0.32, P〈0.05）. Conclusion： Down-regulated expression of Ang-1 may play a crucial role in the development of OSCC. It negatively regulated the angiogenesis of tumor.

The Influence of Gene Polymorphisms on Tobacco and Alcohol-Induced Oral Cancer Risk

Aims: This study examined whether genetic polymorphisms of tobacco and alcohol-related metabolic genes such as GSTM1, GSTT1, GSTP1, CYP1A1, CYP2E1 and DNA repair genes (XRCC1 194Trp, XRCC1 399Gln, and XRCC3 Met) contribute to the risk of developing OSCC. Methods: Patients eligible for inclusion were over 18 years, had pathologically confirmed OSCC and were followed prospectively for at least two years or until death, from December 2000 to December 2004. Ninety-two OSCC patients were included along with 244 subjects from the same hospital, evaluated in the same period as patients without cancer, as the control group. Results: GSTM1 null and XRCC1-194Trp alone increased the risk of OSCC (OR, 2.15;95% CI, 1.2 - 3.6 and OR, 2.02;95% CI, 1.01 - 4.03, respectively). The joint effect of GSTM1 null with CYP1A1 or CYP2E1 polymorphism increased the risk two to threefold. Similar results were observed when XRCC1-194Trp was combined with GSTM1 null or the CYP2E1 polymorphism. By contrast, XRCC1- 399Gln was associated with protection against OSCC. Gene-gene and gene-environmental interactions were mainly detected for CYP1A1 and GSTP1 associated with more than 20 p/y of tobacco and XRCC1-194Trp when more than 30 g/L/d of alcohol was consumed (OR, 8.8;95% CI;1.3 - 45.7). Conclusions: The drug metabolizing and DNA repair enzyme polymorphisms may be informative for clinicians in the preventive management of patients at risk, particularly those with strong smoking and drinking habits.

Establishment of cervical lymph node metastasis model of squamous cell carcinoma in the oral cavity in mice

Background Oral squamous cell carcinoma （OSCC） is the most prevalent malignant tumor in the head and neck region, comprising more than 90% of all oral malignancies. A feasible approach for an animal model to study OSCC lymph node metastasis was established and biological behaviors of three oral squamous cell carcinoma cell lines were compared. Methods After implanting three kinds of cell lines （GDC185, Tca8113, Tca83） into three different anatomical sites in nude mice, namely the tongue, floor of the mouth, and axillary fossa, we observed the tumorigenicity and the metastatic capacity, which was confirmed by histopathology under a surgical microscope. Results The animal model injected with GDC185 cells into the floor of the mouth had the highest rate of neck lymph node metastasis （55.6%） and the cell lines had significantly different biological behaviors. Conclusions Nude mice injected with GDC185 cells into the floor of the mouth could be used as a feasible animal model to study neck metastasis of oral squamous cell carcinoma.