Method: A total of 274 formalin fixed paraffin embedded samples inclusive of 113 oral squamous cell carcinoma (OSCC), 34 moderate/severe dysplasia (SD), 37 mild dysplasia (MD) and 90 normal oral mucosa were retrieved from the Oral Oncology Research Program archival tissue bank. Slides were immunohistochemically stained for hMLH1, hPMS2, hMSH2 and hMSH6 and immunohistiochemical scores for the percentage and intensity of positive cells were recorded. Pearson Spearman’s product-moment correlation coefficient was used to evaluate the lesion severity relationship to MMR protein expression. MMR expression combined with patients’ age and sex were included in a backward stepwise multinomical logistic regression.
Result: A readily apparent inverse correlation between oral disease severity and both obligatory and non-obligatory components of MutLα and MutSα was observed (hMLH1, ρ = -0.715; hPMS2, ρ = -0.692; hMSH2, ρ = -0.728; and hMSH6, ρ = -0.702). Amongst 11 carcinoma in situ cases included in SD category, 9 showed a conspicuous loss of hMSH6 expression from the stratum basale.
Conclusion: Once independently validated, these findings would be a great asset to oral pathologists for diagnosis of oral dysplasia and cancer. In addition, the two-dimensional nature of H&E staining and the ambiguity among the more severe grades of oral epithelial dysplasia, carcinoma in-situ and early OSCC, highlights the imminent need for more robust diagnostic standards for these lesions.
Funding: Australian Dental Research Foundation