Utility of Fine Needle Aspiration Cytology in Discrimination of Breast Cancer Subtypes Based on Biomarker Expression Patterns Compared to Core Needle Biopsy

Abstract

Breast cancer is defined as a group of malignant neoplasms and accounts for up to 23% of all female cancers. It rarely occurs in men. In breast cancer, the level of human epidermal growth factor receptor-2 (HER2) overexpression is said to be a prognostic molecular marker that is used for selection of patients for targeted HER2- therapy. Estrogen receptor (ER) and progesterone receptor (PR) are both prognostic and predictive markers for response to hormonal therapy. Fine-needle aspiration (FNA) provides highly cellular sample. Assessment of HER2, ER and PR status in FNA samples is very important clinically. The study was aimed to validate that fine needle aspiration cytology can be used to assess HER2, ER and PR expression patterns in patients with breast cancer. Cell blocks were prepared from FNA and core needle biopsy material collected from 39 newly diagnosed breast cancer patients and immunocytochemistry (ICC) for HER2 and the hormonal receptors, ER and PR was done. Immunohistochemistry (IHC) for HER2, ER and PR was also done on the corresponding biopsy sections. Both positive and negative quality controls were included in the experiments. The Allred scoring system was used to determine the positivity for PR and ER. The overexpression of HER2 was assessed using a scale of 0-3+ for both proportion and intensity whereby 3+ and above was considered positive. The FNAC cell block results were compared with core biopsy results and breast cancer classified into various types as luminal A, luminal B, HER2 over expression and the triple negative. The results were then compared with those of core biopsy immunohistochemistry using ANOVA. Kappa statistics was done to check the level of agreement. Cell block and biopsy results were compared, for ER there was a concordance of 32/35(91.4%) r=0.842 Sensitivity of 83.3% and specificity of 85.0%. For PR the concordance was 32/35(91.4%) r=0.842 with sensitivity of 84.2% and specificity of 84.2%. For HER2 the concordance was 34/35 (97.1%) r=0.925 with a sensitivity of 88.9% and a specificity of 96.3%. There was moderate agreement between the two methods, k=0.719, p<0.001 .The results obtained from FNA cell blocks are reliable when compared with paired paraffin embedded tissue blocks. Therefore, HER2, ER and PR can be adequately assessed using cell blocks prepared from FNA material.