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Expression of p27/kip1 is down‐regulated in human prostate carcinoma progression
Author(s) -
Fernández Pedro L.,
Arce Yolanda,
Farré Xavier,
Martínez Antonio,
Nadal Alfons,
Rey María J.,
Peiró Nerea,
Campo Elías,
Cardesa Antonio
Publication year - 1999
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199904)187:5<563::aid-path292>3.0.co;2-3
Subject(s) - prostate , intraepithelial neoplasia , pathology , medicine , malignant transformation , carcinoma , metastasis , epithelium , cancer
p27 Kip1 is a cyclin‐dependent kinase inhibitor whose down‐regulation has been observed in several tumour models, including breast, colorectal, and gastric carcinomas. The purpose of this study was to assess p27 Kip1 protein expression in normal and benign prostatic epithelia as well as the possible existence of abnormalities in prostate carcinoma progression. p27 Kip1 expression was immunohistochemically analysed in 51 normal tissue samples, 11 nodular hyperplasias (NH), 22 high‐grade prostatic intraepithelial neoplasias (PIN), 56 localized prostate adenocarcinomas, and 19 metastases. Immunoblotting was performed in ten cases. Normal prostate epithelium and NH showed diffuse and intense p27 Kip1 nuclear expression in most cases. A significant p27 Kip1 down‐regulation was observed in many carcinomas when compared with benign epithelium. Forty‐seven cases (84 per cent) were low p27 Kip1 expressors (<50 per cent positive cells) and nine cases (16 per cent) were high p27 Kip1 expressors. p27 Kip1 down‐regulation was also consistently seen in PIN. Fourteen out of 19 metastases (74 per cent) were low p27 Kip1 expressors. Six metastatic samples had their corresponding primary tumour analysed and three cases showed decreased expression in the metastasis. It is concluded that p27 Kip1 is constitutively expressed in normal and benign prostatic tissue. This expression is clearly down‐regulated in neoplastic progression from the preinvasive lesions through invasive carcinoma and metastases and this therefore occurs in early stages of neoplastic transformation. Copyright © 1999 John Wiley & Sons, Ltd.