engleski

Expression of phosphorylated HER-2 receptor in ductal invasive breast cancer

HER-2/neu oncogene is amplified/overexpressed in 15-30% cases of invasive human breast carcinomas (BC), resulting with a high risk of relapse and poor survival. Due to reduction in BC recurrence and markedly improved survival, treatment of HER-2/neu overexpressing patients with humanized monoclonal antibody trastuzumab (Herceptin®) has become a worldwide treatment of choice. Unfortunately, in some patients responses to trastuzumab vary in magnitude and can be short-lived, with clinical limitations resulting from acquisition of trastuzumab resistance. We evaluated the expression of Tyr-1248 phosphorylated form of HER2 receptor (pHER2) among 83 patients diagnosed with ductal invasive BC. Immunohistochemically detected expression of pHER2 was correlated with known prognostic markers for BC. 42 selected patients were HER2 negative while 41 showed HER2 overexpression and were scheduled for trastuzumab therapy. Overexpressed HER2 was mainly in its phosphorylated/active form (p<0.001). Patients with higher pHER2 expression exhibited more positive axillary lymph nodes (p=0.010), poorly differentiated tumor (p=0.003), smaller primary tumor (p=0.017) and less expressed estrogen receptors (p=0.011). Low pHER2 values were detected in 22.0% of patients overexpressing HER2 while 7.1% of HER2 negative patients showed high pHER2 expression. High pHER2 expression was found in 67% (20/30) of patients sensitive to trastuzumab therapy compared to 27% (3/11) of drug resistant patients. Our preliminary data suggests that evaluation of pHER2 expression may be very important prognostic biomarker. It seems that higher expression of pHER2 determines BCs with increased metastatic potential but better response to trastuzumab therapy while low pHER2 expression among patients selected for trastuzumab, may predict resistance to therapy.

pHER2; phosphorylated HER2; trastuzumab; Herceptin resistance; prognostic factors; breast cancer

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