Down-regulation of CEACAM1 in human prostate cancer: correlation with loss of cell polarity, increased proliferation rate, and Gleason grade 3 to 4 transition.

Many cancers have altered expression of various cell adhesion molecules. One of these is CEACAM1, which has been found to be downregulated in several carcinomas, including prostate cancer. We explored its immunohistochemical expression in a set of 64 total prostatectomy specimens and compared it with that of the epithelial cell adhesion molecule E-cadherin and occludin, a tight junction-associated molecule. The luminal surface of the epithelial cells of normal prostate glands and ducts showed a dense expression of CEACAM1. This pattern prevailed in prostate cancer of Gleason grades 1 to 3 as long as the cells maintained their polarity and formed individual glands. With "fusion" of glands (ie, in the transition to Gleason grade 4), the expression of CEACAM1 was lost in polygonal nonpolar cells and was lost or focally very weak in cells lining a lumen in the cribriform complexes. E-cadherin, which outlined the basolateral cell membranes of contacting neighboring epithelial cells was also downregulated in prostate carcinomas. However, the loss of E-cadherin expression in higher grades was gradual and not related to the Gleason 3 to >4 transition. Occludin was also lost in polygonal (ie, unpolarized) cells of Gleason grades 4 and 5, but remained expressed in all cells facing a lumen in all grades of cancer, which CEACAM1 was not. In conclusion, downregulation of CEACAM1 as well as that of occludin in prostate cancer is associated with loss of cell polarity. It coincides with the formation of the complex glandular architecture of Gleason grade 4 pattern or complete loss thereof in Gleason grade 5 patterns. The proliferative activity, measured as Ki67 labeling index, showed a fourfold increase in the carcinoma cells with lost CEACAM1 expression, supporting previous observations that CEACAM1 regulates cell proliferation. Immunohistochemical analysis of CEACAM1 expression patterns may be useful in assessment of the malignant potential of prostate carcinoma. Copyright 2002, Elsevier Science (USA). All rights reserved.