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MUC1 and Nuclear ß-Catenin Are Coexpressed at the Invasion Front of Colorectal Carcinomas and Are Both Correlated with Tumor Prognosis

¹ Institute of Pathology, ² Department of Visceral and Vascular Surgery, and ³ Center of Biochemistry, University of Cologne, Cologne, Germany

Purpose: Overexpression of MUC1 and cytosolic interaction of the mucin with ß-catenin are claimed to be involved in colorectal carcinogenesis. In vitro data published recently suggest that MUC1 overexpression results in an increase of steady state levels of nuclear ß-catenin. We tried to elucidate the coexpression of both molecules in colorectal cancer to demonstrate possible correlations with clinical, pathological, and prognostic data.

Experimental Design: An immunohistochemical double staining study was performed to characterize the expression and subcellular distribution of MUC1 and ß-catenin in a series of 205 patients with colorectal carcinoma. The results were correlated with clinicopathological variables as well as overall survival.

Results: MUC1 was strongly expressed in the tumor center and at the invasion front in 50% of the cases. Similar results were obtained with regard to nuclear accumulation of ß-catenin at the invasive tumor parts. MUC1 protein expression in the tumor center correlated significantly with a low grade of differentiation, and nuclear ß-catenin in the tumor periphery was more frequent in carcinomas of the left colon and rectum. Overexpression of MUC1 and ß-catenin, as well as their nuclear coexpression at the invasion front correlated with a worse overall survival in an univariate analysis. However, only pathological tumor-node-metastasis staging and MUC1 at the invasion front revealed as independent prognostic factors.

Conclusions: These results suggest that MUC1 and ß-catenin are coexpressed at the invasion front of colorectal carcinomas and that this feature is associated with an accelerated course of disease and worse prognosis.

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