Fas receptor (CD95) & Fas ligand (CD178) expression in patients with tobacco-related intraoral squamous cell carcinoma.

Background & objectives: Fas receptor and Fas Ligand (FasL) system has been implicated in the resistance to apoptosis, insensitivity to chemotherapy and in providing immune privileged status to most of the tumours. However, no reports are available on Fas and FasL expression in patients with tobacco-related oral carcinoma. Therefore, the present study was undertaken to observe Fas and FasL expression and their correlation with clinicopathological features as well as cell cycle parameters. Methods: Immunohistochemistry for Fas, FasL and DNA flow cytometry for cell cycle parameters was successfully done on 41 paraffin embedded tumour and 10 normal samples. The results were evaluated for possible association of Fas and FasL with clinicopathological features and cell cycle parameters. Results: Weak Fas expression was observed on the cell membrane only in 2 of 41 (5%) oral tumours while FasL immunoreactivity was seen in 26 of 41 (63.4%) tumours. In contrast, all ten normal oral tissues exhibited strong cytoplasmic and membrane Fas receptor immunoreactivity but absence of FasL staining. Older patients, greater tumour size and lymph node positivity were found to be associated with high expression of FasL. Significantly higher (P<0.01) expression of FasL was observed in oral tumours with aggressive DNA pattern like aneuploidy and high S-phase fraction. Interpretation & conclusions: Downregulation of Fas receptor and up-regulation of Fas ligand appear to be an important feature of tobacco-related intraoral carcinoma. Association of FasL expression with advanced clinical stage and aggressive DNA pattern suggests that the Fas and FasL system may be used as an important prognostic variable in patients with tobacco-related intraoral squamous cell carcinoma.

Correlation of cyclin D1 expression with aggressive DNA pattern in patients with tobacco-related intraoral squamous cell carcinoma.

Background & objectives: Cyclin D1 has been strongly implicated in cell proliferation particularly in the G1/S checkpoint of the cell cycle, and prognoses in human malignancies. We investigated the correlation between cyclin D1 overexpression and clinicopathological features as well as cell cycle parameters to understand its clinical significance in patients with tobacco-related oral squamous cell carcinoma (OSCC). Methods: Immunohistochemistry for cyclin D1 and DNA flowcytometry for cell cycle parameters was done on paraffin embedded tumour samples from 45 patients with OSCC Results: Higher expression of cyclin D1 was observed only in 30 (66.6%) of 45 cases that correlated with advanced age (P <0.02), higher tumour stage ((P<0.01), histological differentiation and lymph node metastasis (P <0.01). Analysis of nuclear DNA pattern revealed cyclin D1 immunoreactivity in tumours with aggressive DNA pattern such as aneuploidy ((P<0.05) and higher S phase fraction ((P<0.04). Interpretation & conclusions: Higher expression of cyclin D1 in oral cancer appears to be closely linked to cell proliferation, differentiation and lymph node invasion. Pre-operative evaluation of cyclin D1 in biopsy specimen may be useful in planning the most appropriate treatment strategies in patients with tobacco-related OSCC.

Age related changes in Fas (CD95) and Fas ligand gene expression and cytokine profiles in healthy Indians.

Ageing in human and animal models show changes in many aspects of protective immunity, particularly lymphopoenia and progressive decline in immune functions leading to increased frequency of infection and neoplasia. However, the exact mechanism of these defects is still unclear. In this study, elderly subjects showed a decline in CD3+ and CD4+ T-cell subsets as well as serum IL-2 levels. Serum IL-6 was significantly raised while expression of its signaling receptor gp130 was significantly impaired in elderly as compared to the younger ones. Additionally, all the elderly individuals showed constitutive expression of Fas and FasL mRNA; however, none of the younger individuals expressed mRNA transcripts constitutively although induced expression was seen in both the groups. Similarly, frequency of Fas and FasL expressing CD4+ and CD8+ T-cell subsets were significantly (p < 0.001) higher in elderly subjects as compared to the younger ones. Elderly individuals also showed a significantly (p < 0.001) higher frequency of activation induced cell death (AICD). Since interaction of Fas with its cognate ligand (FasL) activates death inducing caspases leading to apoptosis, and gp130 induces anti-apoptotic signal through STAT-3 pathway, these results suggest that the decline in protective immune functions in aged individuals may be related to Fas and FasL mediated apoptosis of peripheral T-cell subsets.

Association of DNA pattern of metastatic lymph node with disease free survival in patients with intraoral squamous cell carcinoma.

BACKGROUND AND OBJECTIVE: Intraoral squamous cell carcinoma (OSCC) is one of the common tobacco related cancers affecting Indian population. These tumours are slow growing, endophytic and are mostly well differentiated. Cervical lymph node is the common site of metastasis of these tumours. In most of the patients cervical lymph node metastasis rather than the primary tumour, affects prognosis. However, no reports are available on the DNA pattern of the metastatic lymph nodes in patients with intraoral squamous cell carcinoma. Therefore, the present study was undertaken to observe DNA pattern of primary tumours and their corresponding metastatic lymph nodes and its association with the clinicopathological parameters and prognosis. METHODS: DNA flow cytometry was successfully carried out on 68 paraffin embedded specimens of the primary tumours and their 22 corresponding metastatic cervical lymph nodes. The findings were evaluated for their possible association with clinicopathological features of the tumour and disease free survival of patients with intraoral carcinoma. RESULTS: Analysis of nuclear DNA patterns revealed 32 (47.0%) diploidy and 36 (52.9%) aneuploidy in primary tumours whereas metastatic lymph nodes showed 7 (31.8%) diploidy and 15 (68.1%) aneuploidy. The aneuploidy group in metastatic lymph node had significantly higher S phase fraction (SPF) (P<0.01) and poor histological grade (P<0.002) as compared to their counterparts with diploidy. DNA pattern of metastatic lymph node further showed a significant association with disease free survival in the log rank test. Aneuploidy and high SPF in metastatic lymph node was found to be associated with early recurrence while DNA pattern of the primary tumour did not show significant association with the disease free survival. INTERPRETATION AND CONCLUSION: It may be concluded that aneuploidy and high SPF in metastatic lymph node might be considered as an important discriminatory risk factor in patients with similarly staged intraoral squamous cell carcinoma.