ASSESSMENT OF TUMOUR PROLIFERATION BY USE OF THE MITOTIC ACTIVITY INDEX, Ki67 AND PHOSPHOHISTONE H3 EXPRESSION IN INFILTRATING DUCTAL CARCINOMA OF BREAST

Abstract

Background Infiltrating ductal carcinoma (IDC) of the breast is a common and aggressive form of breast cancer. Traditional histopathological methods using MAI- Hematoxylin and Eosin (H&E) staining have limitations in accurately assessing tumor proliferation. Immunohistochemical markers like Ki67 and phosphohistone H3 (PHH3) provide enhanced insights into tumor biology and prognostic evaluation. AIMS To assess PHH3 and Ki67 expression in infiltrating ductal carcinoma of the breast and correlate it with mitotic activity index. Additionally, to investigate their association with histological grade and staging of the carcinoma. OBJECTIVES 1. To determine the expression of PHH3 and Ki67 in infiltrating ductal carcinoma breast 2. To correlate mitotic activity index with the expression of PHH3 and Ki67 in infiltrating ductal carcinoma breast 3. To study the association between mitotic activity index, Ki67 and phosphohistone H3 expression with Histological grade and staging of ductal carcinoma breast. Methods A cross-sectional observational study was conducted in the Department of Pathology, Sri Devaraj Urs Medical College, from July 2019 to June 2023. The study included 102 histologically confirmed cases of IDC. Immunohistochemical staining for PHH3 and Ki67 was performed on tumor sections, and the results were compared with H&E staining. Statistical analysis was conducted using SPSS software. xxv Results The majority of the cases (56.9%) were individuals above 50 years of age, with a mean age of 51.46 years. Tumor sizes were predominantly less than 5 cm in 55.9% of the cases, and 52% were at T2 stage. Lymph node involvement was observed in 53.92% of cases, and lymphovascular invasion was present in 34.3%. Tumor-infiltrating lymphocytes (TILs) were mostly below 10% in 66.7% of cases. PHH3 staining identified higher mitotic activity compared to H&E, leading to significant upgrades in mitotic scores and Modified Bloom-Richardson (mBR) grades. Ki67 expression showed a significant correlation with lymph node involvement but not with disease stage. Conclusions PHH3 staining demonstrated superior sensitivity in detecting mitotic figures and provided more accurate grading and prognostic information compared to H&E staining. Ki67 expression was significantly associated with lymph node involvement, highlighting its prognostic value. The findings support the integration of PHH3 staining in routine diagnostic practices to improve the accuracy of breast cancer grading and prognosis.