Abstract

Ki-67 is a proliferation marker that is used not only to categorize patients in luminal A and B subtypes of breast cancers, but also to determine the aggressiveness of the disease in triple negative and human epidermal growth factor 2 (HER2) over expressed molecular subtypes. The present study was designed to evaluate the role of Ki-67 with cut off value of 14% in molecular subgroups and its association with patient prognosis. Immunostaining was performed on histopathologically confirmed sections (n = 278) to assess expression of Ki-67, estrogen receptor (ER), progesterone receptor (PR) and HER2. Immunoreactivity of molecules was recorded as percentage scoring. Adopting a cut off value of 14%, Ki-67 was high in 88%of the cases included in the study. High Ki-67 was significantly associated with pathological parameters including histological grade, advanced stage and nodal/distant metastasis. Immunoexpression of ER, PR and HER2 also showed strong correlation with high expression of Ki-67. Based on the St. Gallen classification, the cases were categorized into luminal A (10%) and luminal B (51%), triple negative (20%) and HER2 enriched (18%). Ki-67 index was also significantly high in 98% of HER2 enriched and 95% of TNBC patients. Interestingly, Ki-67 score with cut off value of 14% proved to be significant in deciphering prognosis in luminal patients. Moreover, high expression of Ki-67 also proved to be a marker of poor prognosis, especially in triple negative patients. We suggest that utilization of IHC4 status i.e. ER, PR, HER2 and Ki-67 along with pathological findings and molecular subtyping can considerably affect clinical as well as therapeutic decisions.

Highlights

  • Breast cancer is the most frequent cause of cancer-related death in females in underdeveloped countries because of lack of screening strategies and limited treatment facilities.[1]

  • Biomarker Status and Molecular Subtyping Biomarkers included in the study were estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2) and Ki-67 with percent positivity of 61, 46, 50 and 88% respectively while the mean Ki-67 index was found to be 44%

  • The majority of ER/PR positive patients presented with initial grades, lower invasive potential having the reverse trend for HER2 and Ki-67

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Summary

Introduction

Breast cancer is the most frequent cause of cancer-related death in females in underdeveloped countries because of lack of screening strategies and limited treatment facilities.[1]. The IHC4 panel consisting of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 receptor (HER2) and Ki-67 (proliferation index marker) is used for patient stratification in different molecular subtypes.[3] According to the St. Gallen consensus conference (2011), the expert panel simplified the therapy indications among breast cancer subtypes based on these 4 biomarkers. The intrinsic classification includes luminal type A and B, Her-2 enriched and triple negative subtype. Ki-67 is a proliferation marker that is used to categorize patients in luminal A and B subtypes of breast cancers, and to determine the aggressiveness of the disease in triple negative and human epidermal growth factor 2 (HER2) over expressed molecular subtypes. High expression of Ki-67 proved to be a marker of poor prognosis, especially in triple negative patients.

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