Evaluation of genetic status of HER-2/neu and aneusomy 17 by fluorescence in situ hybridization and comparison with immunohistochemistry assay from Indian breast cancer patients

The HER-2/neu proto-oncogene is amplified in 15%-25% of breast cancers. In the current study, we evaluated HER-2/neu status of 396 cases of breast cancer by fluorescence in situ hybridization (FISH), and the results were correlated with immunohistochemistry (IHC) for HER-2/neu protein expression. Overall, HER-2/neu amplification was observed in 38.4% of cases. Concordance between IHC and FISH was 90.4% considering only IHC score 0, 1 (negative), and 3 (positive). However, only 37.3% of the IHC score 2 (equivocal) cases showed HER-2/neu gene amplification. A majority of the discordant cases within the IHC negative (score 0 and 1) and IHC positive (score 3) were high-grade tumors. Polysomy 17 and monosomy 17 was seen in 7.3% of the total cases of each. Furthermore, a majority of FISH positive cases were noted in Intraductal Carcinoma grade III and cases with regional lymph nodal metastasis. Polysomy 17 was seen in 7.9% of the FISH positive cases and in 6.3% of the FISH negative cases. Monosomy 17, however was more preponderant in FISH negative cases. We believe that the FISH test should be considered as the gold standard in the estimation of the HER-2/neu status due to its increased sensitivity and better appreciation of aneusomy 17.