Correlation of Expression of Androgen Receptors and P16 in Triple Negative Breast Carcinoma - A Five Years Retrospective and Prospective Study

Abstract

AIM AND OBJECTIVE Triple negative breast carcinoma (TNBC) is an aggressive breast carcinoma, lacking estrogen receptor (ER),progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2neu receptor) amplification, thereby, unresponsive to conventional hormonal therapy. The aim of present study is to examine androgen receptor (AR) and p16 expression in TNBC cases and explore its clinical significance in view of potential AR and p16 targeted TNBC therapy. MATERIAL AND METHOD A total 94 TNBC patients were included in this 5 years (3 years retrospective and 2 years prospective) study, conducted at Department of Pathology, JNMCH, Aligarh. Immunohistochemical stains for AR and p16 were performed and their relationship with TNBC clinicopathological data were analyzed. Positive AR expression was defined as ≥1% nuclear staining wheras positive p16 expression was defined as score of ≥1which in turn calculated as product of intensity score and extent of positivity score of cytoplasmic and nuclear stained cells. RESULT Out of 94 TNBC patients, 92 cases were of invasive carcinoma (NST) and 2 cases were invasive lobular carcinoma.AR was expressed in 38/94 (40.4%) cases, all of which were of invasive carcinoma (NST) type. We observed higher expression rate in postmenopausal women i.e.43.2% (16/37) cases and in patients with age ≥60 years i.e. 66.7% (8/12) cases. Statistical analysis showed significant association of AR + TNBC cases with larger tumor size (p= 0.017412) and lymph node metastases (p= 0.033119). Higher expression rate was found in lower grade and stage III, however statistically insignificant.p16 protein was positively expressed in 72.3% (68/94) of the total TNBC cases. We observed higher expression rate in premenopausal women i.e.78.9%(48/57) cases and in patients with age 40-49 years i.e. 84.4% (27/32) . Significantly higher p16 expression rate was found in grade II (90%) followed by grade I (66.7%) and grade III (65%) (p= 0.04). CONCLUSION TNBC was more common in older age group and had a higher propensity for lymph node metastases. AR positive and p16 positive TNBC cases may represent a breast cancer subtype with unique features that may be amenable to treatment with alternative targeted therapy.