Concordance of HER2 Gene Status between Dual-Color Silver In Situ Hybridization (DSISH) and Fluorescence In Situ Hybridization (FISH) in Invasive Breast Carcinomas (IBCs) after Preoperative Chemotherapy
Youngmee Kwon, Han Sung Kang, Eun Sook Lee, In Hae Park, Geon Kook Lee, Seog Yun Park, Jungsil Ro. National Cancer Center, Goyang, Republic of Korea
Background: HER2 FISH is a quantitative assay for selecting breast cancer patients for anti-HER2 therapy. However, disadvantages of FISH assay include the requirement for a specialized fluorescence microscope, the difficulty of preserving FISH signal for a long time, and the difficulty of evaluating the gene status in the context of tissue morphology. Recently, a brightfield DSISH has been developed to overcome these disadvantages of FISH. The aim of this study is to determine the efficacy of DSISH for the evaluation of HER2 gene status in IBCs after preoperative chemotherapy.
Design: Among 209 IBCs histologically confirmed and surgically resected after preoperative chemotherapy between Jan 2002 and Dec 2005, we included 147 breast resection specimens with available formalin fixed paraffin embedded (FFPE) IBC tissue. HER2 DSISH and FISH were performed in tissue microarray (TMA) sections constructed from representative tumor blocks of IBCs. We compared HER2 DSISH to FISH and also correlated it with HER2 immunohistochemistry (IHC).
Results: The concordance rate of HER2 status between DSISH and FISH was high (93.6%) with perfect interrater agreement (κ=0.8562, p<0.001) in 140 informative cases. Seven (77.8%) of 9 discordant cases were HER2 IHC 2+ cases. All but one of 9 exhibited equivocal DSISH with negative FISH results. The difference of mean value between HER2 DSISH and FISH ratios was statistically significant (0.42±1.41, 95% CI=0.19-0.66, p<0.001) but DSISH ratios were significantly correlated with FISH ratios with high correlation coefficient (γ=0.8613, p<0.001). The result of HER2 DSISH was significantly related to that of HER2 IHC (p<0.001), reflecting the association between HER2 gene amplification and protein overexpression.
Conclusions: The overall concordance between HER2 DSISH and FISH is excellent with HER2/CEN17 ratio using ASCO/CAP criteria. DSISH can be a feasible alternative to FISH for the evaluation of HER2 gene status in IBCs after preoperative chemotherapy.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 44, Tuesday Afternoon