Influence of Immunoexpression of Mismatch Repair Complex Proteins on Disease-Free Survival in Non-Surgically Treated Oropharyngeal Squamous Cell Carcinomas.

Objective: To evaluate the influence of MMR complex protein immunoexpression on disease-free survival in oropharyngeal SCC treated non-surgically.

Materials and methods: 85 cases of oropharyngeal SCC diagnosed and treated at the Ceará Cancer Institute were surveyed, from which clinical-pathological data and paraffin blocks of incisional biopsies were retrieved for immunohistochemical reaction for MSH2, MSH6, PMS2, MLH1 and p16. Disease-free survival was calculated and Kruskal-Wallis and Friedman/Dunn tests, chi-square and Fisher's exact, Log-Rank Mantel Cox and Cox regression were performed.

Results: In p16- tumors, loss of MSH2 expression was associated with shorter disease-free survival (p = 0.035) and mean MSH6 expression was significantly higher than MSH2 (p = 0.001). Loss of MSH2 expression in p16 + tumors was associated with longer disease-free survival compared to p16- tumors. Imbalance in the MSH6/MSH2 ratio in p16 + tumors was associated with longer survival compared to p16- tumors. MLH1/PMS2 imbalance was significantly higher in p16 + with recurrence (p = 0.003). Low MSH2 immunoexpression increased the risk of relapse by 9.10 times (CI95% 1.99 to 83.06).

Conclusion: Microsatellite instability in oropharyngeal SCC is demonstrated by the association between loss of protein expression and its heterodimer imbalance with disease-free survival. It was demonstrated that the imbalance of the MMR complex can consequently lead to resistance to treatment and a decrease in disease-free survival in p16 + oropharyngeal SCC tumors.