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Inactivation of PTEN is associated with a low p27 Kip1 protein expression in breast carcinoma
Author(s) -
Tsutsui Shinichi,
Inoue Hiroshi,
Yasuda Kazuhiro,
Suzuki Kosuke,
Tahara Kouichirou,
Higashi Hidefumi,
Era Shoichi,
Mori Masaki
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21471
Subject(s) - pten , cancer research , medicine , immunohistochemistry , protein expression , breast cancer , breast carcinoma , cell cycle , carcinoma , cell , oncology , pathology , biology , cancer , gene , signal transduction , pi3k/akt/mtor pathway , microbiology and biotechnology , biochemistry , genetics
BACKGROUND It was previously demonstrated that PTEN protein expression is reduced in 67 of 236 (28%) breast carcinomas. Recent experimental studies suggested that the cell cycle inhibitor p27 Kip1 (p27) is a downstream mediator through which PTEN negatively regulates cell cycle progression. METHODS The immunohistochemic expression of p27 and PTEN protein expression was evaluated in a series of 228 invasive ductal carcinomas of the breast. RESULTS PTEN protein expression was found to have decreased in 65 of 228 (29%) cases, while the nuclear accumulation of p27 protein was low in 99 of 228 (43%) cases. A reduced PTEN protein expression correlated significantly ( P = 0.0214) with a low p27 protein expression. Univariate analysis indicated that the patients demonstrating a combined decrease in PTEN and p27 protein expression have a significantly ( P = 0.0044) worse disease‐free survival (DFS) than those with other combinations of these two protein expression patterns, while multivariate analysis indicated that the lymph node status, MIB‐1 counts, and the combination of PTEN/p27 protein expression ( P = 0.0452) are independently significant prognostic factors for DFS. CONCLUSIONS A reduced PTEN protein expression correlated significantly with a low p27 protein expression in breast carcinoma. The finding that the patients with a combined decrease in both protein expressions had a poor prognosis thus suggests that a combined loss of PTEN and p27 function is associated with an aggressive phenotype in breast carcinoma. Cancer 2005. © 2005 American Cancer Society.