Cell kinetics in superficial squamous cell carcinoma of the skin: Role of mismatch repair proteins and telomerase

Background: The cell kinetics of superficial squamous cell carcinoma (SCC) has revealed controversial results due to the heterogeneity of lesions considered, making it more difficult to assess key elements in squamous cell tumor progression. This study analyzes kinetics, cell survival and mismatch repair in a series of high-grade intraepithelial and microinvasive SCC. Design: We selected bowenoid actinic keratosis (HG-AK, 22 cases), SCC in-situ (37 cases) and microinvasive SCC (&lt;3mm depth, 36 cases) that had appropriate archival material. Representative samples were evaluated by standard immunohistochemistry for MCM2 (minichromosome maintenance-2), telomerase, mlh1, msh2 and TP53. The immunoexpression was assessed in the whole lesion and the positive cells as percentage of tumor cells. Appropriate controls were run in each sample. The results were statistically compared using analysis of variance and Student t-test, and considered significant if P&lt;0.05 Results: Both MCM2 and TP53 expression increased from HG-AK to microinvasive SCC, revealing no statistically significant differences (Table). Telomerase showed significantly upregulated expression in microinvasive SCC when compared with intraepidermal lesions (P=0.0037) and mlh1 expression was significantly down-regulated in HG-AK (P=0.0022). AK-HG/ SCC IN-SITU/ SCC MICRO<br>MCM2, %Cellularity/ 9.00/ 19.17/ 28.58 TELOMERASE, %Cell/ 55.75/ 48.08/ 72.39 MLH1/MSH2, %Cellularity/ 7.73/ 19.04/ 20.15 % NULL/ 58.00/ 12.70/ 10.86 TP53, %Cellularity/ 30.50/ 32.78/ 36.63<br>Conclusion: 1) The invasion capacity in superficial SCC is marked by up-regulation of telomerase in lesions preferentially expressing abnormal TP53. 2) The differential growth pattern of intraepidermal SCC is kinetically related with down-regulation of mismatch repair proteins.