Immunohistochemistry, next generation sequencing (NGS), and whole exome sequencing concordance in HER2 testing in uterine serous carcinoma: a retrospective analysis.

BACKGROUND

HER2-targeted treatments are an important therapeutic option for a subset of uterine serous carcinoma (USC) patients. We evaluated the concordance of routine immunohistochemistry (IHC) testing and fluorescence in situ hybridization (FISH) for HER2 expression versus next generation sequencing (NGS) by a commercial platform (Foundation Medicine), and comprehensive whole exome sequencing (WES).

METHODS

Two groups of USC patients with IHC and FISH results for HER2 were compared for concordance with matched NGS data (152 USC patients) and WES (76 USC patients) performed at the Yale Center for Genome Analysis (YCGA). Clinical HER2 positivity was defined as 3+ IHC staining or 2+ IHC staining with reflex gene amplification utilizing fluorescent-in-situ-hybridization (FISH). NGS HER2 positivity was defined as ERBB2 amplifications identified in the NGS/WES report.

RESULTS

In the IHC/NGS group, the overall correlation was 81 % (p < 0.001), which improved to 85 % (p < 0.001) when IHC/FISH and NGS were performed on the same pathology tissue block of a particular specimen. In the IHC/WES group, the overall correlation was similar at 82 % (p < 0.001). NGS captured 1 additional patient missed by IHC/FISH, while WES captured 11 additional patients not identified by IHC/FISH.

CONCLUSIONS

The correlation of HER2 IHC/FISH with NGS and WES ranges between 80 and 85 %, with improvement in correlation when testing is performed on the same tissue block. WES may be superior to commercially available NGS platforms in the detection/identification of HER2 treatment-eligible patients. While highly correlated, these results confirm that IHC should not be abandoned in the evaluation of patients eligible for HER2-targeted therapy.