Correlation of proliferative index with various clinicopathologic prognostic parameters in primary breast carcinoma: A study from North India

Abstract

Aim: Routine assessment of cell proliferation is recommended in the pathologic evaluation for all breast cancers. Considering the poor reproducibility and interobserver variability in mitotic counts, Ki-67 is an easily available and reliable substitute for mitotic counts and has been shown to have a significant relationship with the histologic grade of malignancy and the mitotic activity of tumors. Our study aimed at exploring Ki-67 expression and studying its correlation with other established prognostic parameters.

Materials and methods: Seventy-five cases of primary breast cancer undergoing radical or modified radical mastectomy constituted the study group. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)/neu, and Ki-67 was assessed in each case. Ki-67 labeling index (Ki-67-LI) was estimated as the number of positive nuclei divided by total number of nuclei scanned counting a minimum of 1000 cells in 10 selected high power fields that displayed the highest immunoreactivity and was expressed as percentage. Ki-67 expression was correlated with various clinicopathologic prognostic parameters including age, tumor size, tumor type, axillary lymph node status, and histologic tumor grade.

Results: A statistically significant direct association was observed between Ki-67-LI and tumor size, histologic grade and Nottingham prognostic index. A statistically significant inverse association was observed between Ki-67-LI and ER and PR expression. However, no association was observed between Ki-67-LI and menopausal status, lymph node involvement and HER2/neu expression.

Conclusion: Based on our results, we concluded that modified Bloom-Richardson (MBR) grading has been recognized as a treatment related indicator. The accuracy and reliability in grading have always been a matter of concern, hence, the reproducibility of grading should be enhanced. Ki-67-a proliferation marker is easily identified and provides comparable accurate information. In contrast to poor reproducibility of mitotic counts, Ki-67 can achieve high agreement between pathologists; is more reproducible; adds complementary value to the MBR grading system and correlates well with other clinicopathologic parameters. It may act as a significant prognostic indicator for routine clinical use and be helpful for selection of adjuvant treatment. It can also add value in categorizing Grade II tumors into two prognostic subgroups with prognosis equivalent to Grades I and III, respectively.

Keywords: Breast carcinoma; Ki-67; Ki-67 labeling index.