Inactivation of PTEN is associated with a low p27Kip1 protein expression in breast carcinoma.
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 p27Kip1 (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.
Tsutsui
Shinichi
S
Department of Breast Surgery, Matsuyama Red Cross Hospital, Bunkyo, Matsuyama, Japan. tsutsui@lime.ocn.ne.jp
Inoue
Hiroshi
H
Yasuda
Kazuhiro
K
Suzuki
Kosuke
K
Tahara
Kouichirou
K
Higashi
Hidefumi
H
Era
Shoichi
S
Mori
Masaki
M
D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D044584:Carcinoma, Ductal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011379:Prognosis
D014408:Biomarkers, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human