Ki67 expression in oestrogen receptor positive breast ductal carcinoma

Abstract

Aims Gene expression profiling classifies ER positive breast cancer into two main subtypes.1 Luminal A tumours have a better prognosis than luminal B tumours, are tamoxifen sensitive and derive less benefit from adjuvant chemotherapy. A high Ki67 proliferation index (>14%) has been proposed as a cost-effective means to distinguish luminal B from luminal A tumours.2 We aimed to assess the reproducibility of classifying ductal carcinomas into luminal subtypes by Ki67 expression using manual scoring and image analysis. Method Immunohistochemistry for Ki67 was performed on ninety ER positive invasive ductal breast carcinomas diagnosed at Austin Pathology. The Ki67 index was assessed semi-quantitatively by two pathologists and quantitatively by image analysis using Aperio digital scanning system. Correlation between scoring methodologies and BRE grade were assessed. Results Preliminary results show a correlation between high Ki67 index and high BRE grade. Manual Ki67 index scoring and Aperio image analysis scoring results were well correlated, but indicate a differing proportion of tumours exceeding the 14% cut-point. Discussion Most ductal carcinomas were classifiable as Ki67 low or Ki67 high by either technique, though different methods may require validation of differing cut-points. The heterogeneous distribution of Ki67 expression can limit the precision of quantitative measurement. Gene expression profiling classifies ER positive breast cancer into two main subtypes.1 Luminal A tumours have a better prognosis than luminal B tumours, are tamoxifen sensitive and derive less benefit from adjuvant chemotherapy. A high Ki67 proliferation index (>14%) has been proposed as a cost-effective means to distinguish luminal B from luminal A tumours.2 We aimed to assess the reproducibility of classifying ductal carcinomas into luminal subtypes by Ki67 expression using manual scoring and image analysis. Immunohistochemistry for Ki67 was performed on ninety ER positive invasive ductal breast carcinomas diagnosed at Austin Pathology. The Ki67 index was assessed semi-quantitatively by two pathologists and quantitatively by image analysis using Aperio digital scanning system. Correlation between scoring methodologies and BRE grade were assessed. Preliminary results show a correlation between high Ki67 index and high BRE grade. Manual Ki67 index scoring and Aperio image analysis scoring results were well correlated, but indicate a differing proportion of tumours exceeding the 14% cut-point. Most ductal carcinomas were classifiable as Ki67 low or Ki67 high by either technique, though different methods may require validation of differing cut-points. The heterogeneous distribution of Ki67 expression can limit the precision of quantitative measurement.