Maspin is up‐regulated in premalignant prostate epithelia

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Abstract
BACKGROUND Maspin, a novel serine protease inhibitor, has been shown to inhibit prostate tumor cell motility and invasion in vitro and to inhibit prostate tumor growth and metastasis in vivo. Maspin expression in high‐grade prostate carcinoma (PC) is reduced compared with that in low‐grade PC. Interestingly, however, compared with low‐grade PC, benign secretory prostate epithelial cells express significantly less maspin. This observation appears paradoxical to a putative tumor suppressive role of maspin in prostate carcinogenesis, and this finding issue needs to be clarified. METHODS We examined maspin expression simultaneously in benign basal cells, benign secretory cells, high‐grade prostate intraepithelial neoplasia (HGPIN), low‐grade PC, and high‐grade PC in 46 radical prostatectomy specimens plus 51 autopsy prostate glands by a combination of immunohistochemistry and in situ hybridization. RESULTS Benign basal cells consistently expressed maspin at a high level. In PC, the loss of basolateral maspin expression coincides with loss of the basal cell layer. Maspin expression in secretory cells, on the other hand, appears to undergo a biphasic differential regulation, i.e., essentially absent in benign secretory cells, dramatically up‐regulated in HGPIN, then progressively down‐regulated through low‐grade PC to high‐grade PC. Maspin expression in PC is inversely correlated with tumor grade. Furthermore, maspin expression in HGPIN is inversely correlated with the Gleason's grade of the adjacent PC. CONCLUSIONS An up‐regulation of maspin expression precedes, rather than occurs at, the critical transition from premalignant prostate lesion of HGPIN to PC. Our data suggest maspin may mark an important transitional phase and play an important role in the premalignancy of the prostate gland. Prostate 53: 255–262, 2002.