The influence of desmocollin 1-3 expression on prognosis after curative resection of colorectal liver metastases.

ABSTRACT

PURPOSE: Prognosis after curative resection of colorectal liver metastases is hard to determine based on clinical parameters; biomarkers are therefore needed. The purpose of this study was to determine the value of desmocollins (DSC) as potential biomarkers. Desmocollins are responsible for cell-cell adhesion in epithelial tissue; their loss may lead to reduced cellular adhesion and facilitate cellular migration, enabling tumor cells to form distant metastases. We analyzed DSC expression in colorectal liver metastases with respect to the risk of recurrence following liver resection. METHODS: Tissue microarrays from 257 consecutive patients who underwent R0-resection of colorectal liver metastases were constructed. RESULTS: Low expression of DSC 1, 2, and 3 was observed in 55, 54, and 79 % of liver metastases. There was no correlation between site or stage of the primary tumor, presence of extrahepatic tumor, grading, size or number of metastases, and desmocollin expression. Primary tumor stage I or II (p = 0.005) and no or few lymph node metastases (p < 0.001) were associated with a significantly better disease-free survival on univariate analysis. These parameters reached only marginal significance on multivariate analysis (p = 0.059 and p = 0.052, respectively), as did desmocollin 3 expression (p = 0.050). In the subgroup of patients with stages III-IV primary tumors, however, multivariate analysis showed a significant correlation between DSC 3 expression and disease-free survival after liver resection (p = 0.009). CONCLUSIONS: Reduced expression of DSC3 correlated with an increased risk of developing tumor recurrence after resection of liver metastases. These findings may be helpful in selecting high-risk patients who might benefit from multimodal therapy.