Protein Expression Of PTEN In Primary Breast Cancer Is Linked To Prognosis, But Not Associated With P27～(kip1) And Cyclin D1 Expression

Objective To study the localization and expression lever of PTEN, a tumor suppressor gene. And their relationship to p27klpl protein and cyclin Dl which are presumed downstream targets of PTEN, and clinical pathologic factors as well as the prognostic factors in 61 primary breast cancer patients. Methods Formalin-fixed paraffin embedded tissues from 61 women with primary breast cancer were evaluated for PTEN protein expression by immunohistochemical methods. Results were compared with clinical pathologic parameters, and p27 lpl and cyclin Dl protein expression which were evaluated by immunohistochemical methods, too. Results PTEN showedcytoplasm staining and p27klpl showed in nuclear, whereas overexpression of cyclin Dl immunostaining was mostly nuclear, however, weak cytoplasmic staining was also observed. Four(6.6%) of 61 breast tumors had loss of PTEN expression(0 to 10% cells stained), 25 samples (41.0%) had reduced staining(10% to 50% cells stained), and the rest (52.5%) were PTEN-positive (>50% cells stained). Of the 61patients, p27klpl expression was low (0 to 10% cells stained and 10% to 50% cells stained) in 39(63.9%) and high (>50% cells stained) in 22(36.1%), respectively. Cyclin Dl expression was low(0 to 10% cells stained) in 19(31.2%) and high(10% to 50% cells stained, >50% cells stained) in 42(68.8%), respectively. PTEN expression level was correlated with axillary lymph node status, and loss of estrogen receptor staining, and metastasis. On univariate analysis, better disease-free survival in patients with higher PTEN expression(>50% cells stained) than in those with lower expression(P=0.0101). However, there was no correlation between p27klpl and cyclin Dl expression and PTEN expression. Conclusions Lower expression of PTEN gene protein product is associated with poor outcome , and PTEN play a prominent role in breast cancer. PTEN as a candidate tumor suppressor favors prognosis of human breast cancer. However, in vivo, p27klpl and cyclin D1 might not be the primary downstream targets, at least in breast cancer.