PTEN is a
tumor suppressor that negatively regulates the PI3 K-AKT signaling pathway which is involved in the pathogenesis of many different
tumor types and serves as a prognostic marker in
breast cancer. However, the significance of the role of PTEN in Middle Eastern ethnic
breast cancer has not been explored especially with the fact that
breast cancer originating from this ethnic population tend to behave more aggressively than
breast cancer in the west. In this study, we analyzed PTEN alteration in a tissue microarray format containing more than 1000 primary breast
cancers with clinical follow-up data. Tissue Microarray sections were analyzed for
protein expression and copy number change using immunohistochemistry and fluorescence in situ hybridization. Loss of PTEN immunostaining was observed in 77 % of the cases. PTEN loss was significantly associated with large
tumor size (p = 0.0030), high grade (p = 0.0281),
tumor recurrence (p = 0.0333), and
triple-negative breast cancers (p = 0.0086). PTEN loss in
triple-negative breast cancers was significantly associated with rapid
tumor cell proliferation (p = 0.0396) and poor prognosis (p = 0.0408). PTEN deletion was found only in 60 cases (6.4 %). Loss of
PTEN protein expression occurs at high frequency in Middle Eastern
breast cancer. PTEN inactivation may potentially lead to an aggressive behavior of
tumor cells through stimulation of
tumor cell proliferation. Furthermore, PTEN signaling pathway might be used as potential therapeutic target in
triple-negative breast cancers since loss of its expression is shown to be significantly associated with this aggressive subtype of
breast cancer.