Intratumoral Heterogeneity for Ki-67 Index in Invasive Breast Carcinoma: A Study on 131 Consecutive Cases

Introduction: In addition to conventional histopathologic parameters, the assessment of proliferation is a major factor in treatment decision in breast carcinoma patients. The aim of this study was to assess whether Ki-67 heterogeneity in invasive breast carcinomas could have an impact over treatment decision. Materials and Methods: Immunohistochemistry for Ki-67 was evaluated in resection specimens of 131 consecutive invasive breast carcinomas. Heterogeneity was defined as the presence of a low ( < 17%) and high (> 35%) proliferative activity within the same tumor in the same histologic section. The rest of the cases were defined as homogenous. Clinical-pathologic features were also analyzed. Results: A total of 107 (81.67%) of the cases were homogenous and 24 of 131 cases (18.32%) showed heterogeneity as defined above. Among these, 10 (41.6%) cases showed a gradient of increasing staining toward the tumor edge and 14 (58.4%) cases showed hot spots. In general, the proliferative activity varied from 1% to 90% in different areas of the tumor. A higher incidence of breast carcinoma was observed after menopause in both groups (83.33% in heterogeneous cases and 79.43% in homogeneous cases) (P = 0.783). These groups were similar as far as the most frequent histologic types were concerned: no special type (95.83% vs. 56.07%) (P = 0.0001). Tumor histologic grade, T and N stage were similar in both groups. We noted a higher proportion of stage N3 cases in the heterogeneous tumor group (54.16% vs. 34.57%) (P = 0.14). Prognostic markers analysis in the heterogeneous cases revealed 100% positivity for hormone receptors (compared with 94.65%) and a much higher proportion of HER2-negative cases (87.5% vs. 73.83%) (P = 0.19). Conclusion: As Ki-67 heterogeneity can be encountered in breast carcinomas and Ki-67 value could have an impact on clinical decisions, it is mandatory to evaluate the whole specimen and not only the core biopsy specimen and to correlate it with mitotic count.