Expression of alpha-1-antichymotrypsin in prostate carcinoma

Abstract

Prostate specific antigen (PSA) is a glycoprotein with the enzymatic activity of serine protease, the gene which is encoded in the human glandular kallikrein gene locus. Catalytically active PSA released into serum may be inactivated by a complex formation with alpha 1ACT (ACT) and alpha 2MG (MG), two major protease inhibitors. The serum complex-to-total PSA ratio can be used as a marker for the differentiation between prostate carcinoma (PCa) and a benign lesion because of a significant elevation of PSA binding to ACT in PCa. Apparently higher immunohistochemical expressions of PSA and ACT have been reported in PCa of low Gleason scores when compared with benign lesions. The fact that only normal secretory epitheliums are capable of producing ACT was recently proved by immunohistochemical and in situ hybridization methods. Our immunohistochemical study of ACT showed a tendency toward stronger expression in high Gleason grade PCa than in low Gleason grade Pca. Prostate intraepithelial neoplasia (PIN), as well as BPH, seldom react to ACT. Expression of ACT in normal ducts or acini was influenced by their location. In a normal prostate, expression of ACT was predominantly in secretory epithelial cells, with a minority of basal cells and rarely in the interdigitating neuroendocrine cells. Whereas the potency of ACT production in epithelial cells almost always appeared to be suppressed under normal conditions, it was noted that a strong expression of ACT was apparent in the normal ducts or acini near a high grade carcinoma with a weak reaction to ACT. ACT expression is much more enhanced in high grade carcinomas and in the residual normal acini adjacent to carcinomas of low ACT expression, presumably representing scale down the elevated PSA.