Correlations between HER2 Expression and Other Prognostic Factors in Breast Cancer: Inverse Relations with the Ki-67 Index and P53 Status

Background: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases. Materials and Methods: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as ${\geq}10%$ positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3+ by IHC. For HER2 (2+), FISH was performed to determine HER2 positivity. Results: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor size<2cm and also $Ki-67{\geq}20%$ as compared to the HER2-positive group. Conclusions: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index ${\geq}20%$ in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-$67{\geq}20%$ had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.