Differential expression of C-CAM cell adhesion molecule in prostate carcinogenesis in a transgenic mouse model

Purpose: The transgenic adenocarcinoma of mouse prostate (TRAMP) model, in which various grades of prostate intraepithelial neoplasia (PIN) and prosta te cancer with metastases can be reproducibly generated, is a paradigm for prostate disease progression. We have previously shown that C-CAM, an adhes ion molecule, can suppress the growth of prostate cancer. In this report, w e describe immunohistochemical characterization of differential expression of C-CAM at various stages of prostate tumorigenesis in the TRAMP model. Materials and Methods: We sampled prostate specimens and periaortic lymph n odes from TRAMP mice. Indirect immunohistochemical staining with a polyclon al anti-C-CAM antibody was performed on the formalin-fixed, paraffin-embedd ed specimens. After castration at 12 weeks of age, the TRAMP mice developed androgen-independent prostate cancer (AIPC) and lymph node metastasis at 1 8 to 24 weeks of age. Samples from these castrated mice were also analyzed. Results: C-CAM protein was expressed in the normal prostate epithelia of no n-transgenic and TRAMP mice as well as in low-grade PINs in TRAMP mice. Exp ression was uniform on the luminal surfaces of these epithelia. C-CAM expre ssion was noticeably reduced and the staining pattern heterogeneous in some high-grade PINs. C-CAM staining was generally absent in prostate cancer an d metastatic lymph nodes. Androgen independent prostate cancer and its meta static tumors generated in castrated TRAMP mice were also C-CAM negative. Conclusions: C-CAM expression correlates with the differentiation states of prostate epithelia and is down regulated early in prostate tumorigenesis i n the TRAMP model.