MLH1, MSH2, MRE11, and XRCC1 in Oral Leukoplakia and Oral Squamous Cell Carcinoma.

BACKGROUND: DNA damage is accumulated in the cells over time as the result of both exogenous and endogenous factors. The objective of this study was to analyze the immunohistochemical expression of the repair proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Paraffin blocks were selected from the archives of the Laboratory of Hospital Clinico Universitario de Santiago de Compostela, Spain. The sample was composed of 16 cases of OL without dysplasia, 14 cases of OL with dysplasia, and 15 cases of OSCC. The patients' clinical data were collected and immunohistochemical analysis was performed for MLH1, MSH2, MRE11, and XRCC1. The data were submitted to the χ2 and the Kruskal-Wallis (P≤0.05) tests. RESULTS: MSH2 was overexpressed in OSCC (P=0.020) and was positive in 100% of patients with OL with dysplasia or OSCC (P=0.019). Positivity for MLH1 was significantly associated with comorbidity (P=0.040), especially in patients who presented with 2 or more pathologies (P=0.028). XRCC1 positivity was also associated with comorbidity (P=0.039). No significant associations were found for the MRE11A expression. Although the simultaneous positivity for the 4 markers was observed in presence of comorbidities (P=0.006). CONCLUSIONS: This study supports the effect of the overexpression of MSH2 protein in samples of OL with dysplasia and OSCC, most notably in patients who present with comorbidities and negativity for OL without dysplasia.

p21{Waf1/CIP1} is a poor diagnostic and prognostic marker for OSCC although its expression increases in patients with N1 regional metastasis.

OBJECTIVES: Downregulation of p21{Waf1/CIP1} (a cyclin-dependent kinase inhibitor) has been reported for mouth cancer. The goal of this article is to quantitatively report expression of p21{Waf1/CIP1} and evaluate its relationship with the clinical and prognostic factors. MATERIALS AND METHODS: this is a retrospective study of 68 patients diagnosed with OSCC. We constructed a tissue microarray to develop an immunohistochemical assessment of p21{Waf1/CIP1} expression. A multivariate analysis using a forward-selection stepwise regression model (Cox, 1972) for predicting survival was performed. RESULTS: The quantitative expression of p21{Waf1/CIP1} showed a statistically significant relationship with the risk of lymph node metastasis, showing a higher expression in patients with homolateral single nodes of less than 3 cm (N1) (X{2}=6.58; p< 0.05). We found no statistically significant relationship with any other clinical or pathological parameters. The Cox univariate regression analysis verifies that the effect of the value of p21{Waf1/CIP1} on survival was not statistically significant (p=0.6). The best predictive multivariate Cox analysis included the covariates: recurrence, p21{Waf1/CIP1}, gender, stage, and dysplasia in the adjacent margin. All these variables showed a statistically significant relationship with survival, except p21{Waf1/CIP1}. CONCLUSION: quantitative determination of p21{Waf1/CIP1} standardizes and facilitates its analysis. Although its expression increases in patients with N1 regional metastasis, the loss of p21{WAF1/CIP1} does not seem to have any relationship with the clinical and pathological variables of the tumors.