Her-2/neu Oncogene Amplification by Fluorescence In Situ Hybridization and Protein Overexpression on Immunohistochemistry in Breast Cancer

Objective: To investigate the concordance and discordance between the test results of Her-2/neu by immunohistochemistry (IHC) and flourescence In Situ hybridization (FISH) in breast cancer cases. Study Design: Descriptive cross-sectional study. Place and Duration of Study: Department of Histopathology, Dr. Ziauddin Hospital, Karachi, from 2011 to 2016. Methodology: Forty-three specimens of invasive ductal carcinoma of breast were evaluated for grade and Her-2/neu status using IHC and FISH methods. Concordance and discordance between their results was determined. Results: There is 100% concordance between FISH and IHC in cases scoring 0, 1+ (negative) and 3+ (positive) immunostaining. Tumour cases scoring 2+ immunostaining showed amplification in 69.2% cases. All grade-I tumours were non-amplified on FISH, while most of the grade-III tumours showed Her-2/neu amplification on FISH. There is significant association of Her-2/neu IHC with tumour grade and FISH (p<0.05). A fairly high proportion i.e. 69.7% of cases showed Her-2/neu gene amplification. There was high concordance between Her-2/neu testing on IHC and FISH, (Kappa co-efficient 0.466, p <0.001). Conclusion: Her-2/neu amplification increases with increasing grade of breast cancer. A high proportion of Her-2/neu gene amplified cases indicates aggressive disease in that area and need for FISH testing on large scale, which is the gold standard for equivocal cases on immunohistochemistry.