Expression and prognostic significance of P-glycoprotein [MDR-1] in infiltrating duct carcinoma of the breast

ABSTRACT

Breast cancer is a major public-health issue worldwide. It is the most common cancer in women constituting 22% of all cancer cases world wide. Until recently, breast cancer was subclassified on the basis of cellular morphology and the presence of several receptors, namely ER, PgR, and the Her2, identified by immunohistochemistry. The present study was designed aiming to determine the expression of P-glycoprotein in infiltrating ductal carcinoma [IDC] patients, to correlate the expression of P-glycoprotein with other clinical and pathological parameters and to ascertain whether pretreatment detection of P-glycoprotein in patients with breast cancer could be utilized as a reliable predictor of poor prognosis. The present study constituted thirty nine cases of IDC received at the pathology department during one year beginning at January 2004. For all studied cases, routine histopathologic diagnosis and immunodetection of P-gp, ER, PgR and Her2 were carried on. Retrospective follow up of the patients for period of 2-3 years after the mastectomy operation was carried on with statistical analysis of the results. ER positive status was encountered in 10 cases [25%]. PgR positive status was encountered in 14 cases [35.9%]. A statistically significant association was detected between both ER and PgR expression and nuclear grade [P=0.002, p=0.017]. Her 2 positive immunostaining was detected in 12 cases [30.8%]. P-gp was detected in 26 cases [66.7%]. Statistically significant association between P-gp and Her2 expression was found [p=0.027]. The present study detected that ER negativity [p=0.009], nuclear grade III [P=0.06] and triple-negative molecular subtype [P=0.017] were associated with poor local recurrence-free survival [LRFS]. Her2 positivity [P=0.06] and lymph node metastasis [P=0.08] were associated with poor distant-metastasis free survival [DMES]. Her2/neu IDC that express P-gp had the poorest DFS. Pretreatment detection of P-gp is of great value to predict the response to chemotherapy in patients with Her2 -positive and triple negative infiltrating ductal carcinomas