title: Expression of p 16 protein in prostatic adenocarcinomas, intraepithelial neoplasia, and benign/hyperplastic glands.
abstract: The tumor suppressor gene CDKN2/MTSI(p16(INK4)) may be inactivated by point mutations, deletions, or methylation in many tumor types. In prostate cancer, a very low frequency of point mutations has been reported, but deletions of 9p21 and inactivation by methylation are observed more frequently. The purpose of this study was to assess the expression pattern of the CDKN2 protein product p 16 in a series of 104 prostatic adenocarcinomas treated by radical prostatectomy, using immunohistochemical detection on archival, paraffin-embedded material. Nuclear staining was completely absent in 13 (13%) of 104 cases, whereas cytoplasmic staining was found in 99 (95%) of 104 carcinomas. Significant differences were found when comparing the staining intensity of carcinomas and coexisting prostatic intraepithelial neoplasia (PIN) with benign/hyperplastic glands. In 86 (95%) of 91 cases the overall staining intensity of carcinomas was stronger than the reactivity in benign/hyperplastic glands, which were most often weakly stained. In 71 (95%) of 75 cases the staining intensity of PIN was stronger than in benign/hyperplastic glands, a contrast also observed within single glands. However, p16 immunostaining in carcinomas was not prognostically important and it was not associated with standard clinicopathologic parameters. Our results support that CDKN2/plb is inactivated in only a small proportion of localized prostate cancers. The increased p16 staining of carcinomas/PIN in comparison with benign/hyperplastic glands suggests that p 16 protein may be involved in early stages of prostate tumorigenesis by mechanisms other than CDKN2/p16 gene inactivation, and the possibility of using p(16) immunostaining as a marker for PIN is discussed.
authors.affiliation: Department of Pathology, The Gade Institute, Department of General Surgery, University of Bergen, Bergen, Norway.
authors.forename: O J
authors.initials: OJ
authors.lastname: Halvorsen
authors.forename: S
authors.initials: S
authors.lastname: Haukaas
authors.forename: P Å
authors.initials: PÅ
authors.lastname: Høisæter
authors.forename: L A
authors.initials: LA
authors.lastname: Akslen