Gradual loss of functional gap junction within progression of colorectal cancer -- a shift from membranous CX32 and CX43 expression to cytoplasmic pattern during colorectal carcinogenesis

Abstract

The aim of this study was the assessment of expression and location of CX32 and CX43 in colorectal adenomas and carcinomas as well as analysis of expression of these proteins in association with clinical and pathological features of tumors and evaluation of mutual relationships between CX32 and CX43.

Patients and methods: The study included 151 primary colorectal carcinoma and 71 colorectal adenomas. The control group comprised 30 colon samples. Connexins were detected with immunohistochemistry.

Results: There was a lack of membranous distribution of connexins or a shift from moderately membranous immunoreactivity to predominantly cytoplasmic accumulation of CX32 and CX43 in studied colon tumors. Mentioned alterations were found in adenomas and augmented in cancer. Expression of Cx32 was significantly associated with grading of colorectal cancer, implicating a role of intracellular CX32 in regulation of tumor growth and differentiation. A strong correlation was present between CX32 and CX43 in node-positive cases and absent from node-negative ones.

Conclusion: To our knowledge, our study is the first illustration for a gradual loss of functional gap junctions within progression of colorectal neoplasia. An intracellular location of connexins, the site of their common and the most frequent detection within cancer cells in our study may be of significance. Independently of its role in functional gap-junctions, cytoplasmic CX32 could be involved in cancer differentiation, resulting in a higher rate of CX32 positive moderately differentiated tumors (G3) than poorly differentiated CX32-positive ones (G3).