Smoothelin as a marker of muscularis propria in biopsies of colorectal carcinomas.

Abstract

e14076 Background: Preoperative staging is of eminent importance for the treatment of colorectal carcinomas (CRCs). Especially the distinction of carcinoma in situ (not permigrating the muscularis mucosae (MM)), the pT1 stage (limited to the submucosa) and pT2 and above, infiltrating the muscularis propria(MP) in endoscopic biopsies could change the therapeutic regimen. Smoothelin (SMT) is a robust marker of the MP in normal colon, which is not expressed in MM; therefore, we analysed its expression in biopsies and resections of CRCs, to test its predictive value in staging of CRCs. Methods: 50 CRCs, diagnosed in biopsy particles and staged in the surgical specimens were analysed by IHC for expression of smoothelin (MoAb R4A, DCS Hamburg), Desmin and smooth muscle antigen SMA (all DAKO ) in MP and MM in the vicinity of invading carcinoma cells and in distance to the tumor. Semiquantitative grading REMMELE. Results: Desmin and SMA were consistently expressed in the smooth muscle cells of MM and MP near and distant to carcinoma cells. SMT showed no or little expression in the muscle cells of MM. The penetration of the MM by tumorcells did not alter their reactivity. In the MP however, the invasion by carcinoma cells caused a total or subtotal loss of SMT in the cytoplasm of the smooth muscle cells. The diameter of the nucleus and the longitudinal axis in SMT-deprivated cells did not change, but the transversal diameters of the cells were decreased. Reducing the mechanical stress of smooth muscle cells diminishes also the expression of SMT. No predictive correlation between biopsy-estimated depth and real depth of tumorinfiltration was seen. Conclusions: Expression of SMT correlates to functional status of the cells. The reliable difference in the IHC-expression of SMT in MM and MP in normal colon is not seen in the colon near carcinomas: the muscle cells of MP also lose their STM expression. Thus, negativity for SMT in smooth muscle cells near tumorcells does not necessarely proof, that this will be MM; as well, it could be SMT-deprivated cells of the MP. To rely upon SMT in biopsies for the determination of the depth of invasion is highly dangerous.