Relationship of HER2 alteration and MSI status in colorectal adenocarcinoma.

Abstract

121 Background: The impact of HER2 somatic mutations in colorectal carcinoma (CRC) has not been well studied and its relationship with MSI-H is an open question. Methods: From February 2017 to February 2020, CRC patients who received tumor specimens next-generation sequencing and detail record of clinic-pathologic information were enrolled. HER2 alteration and its relationship with MSI-H were analyzed. Results: There were totally 55 patients (7.5%) with HER2 alteration including 29 (4.0%) HER2 somatic mutations, 24 (3.3%) HER2 gene amplification, and 2 patients (0.2%) with both HER2 mutations and amplification. For HER2 mutated cases, 48.3% were MSI-H, while none of HER2 amplification cases were MSI-H. MSI-H was found in 5.2% in our cohort and 36.8% MSI-H patients were HER2 mutated. MSI-H had less frequency of lung metastasis. The mPFS for first line chemotherapy was significantly higher in MSS cases than in MSI-H cases, 11.5 months vs 3.5 months, P = 0.032. MSI-H patients with HER2 mutation had significantly worse mPFS for PD-1 antibody than those without HER2 alteration, P = 0.036. Conclusions: High MSI-H rate is found in HER2 mutated cases but no MSI-H in HER2 amplification cases. MSI-H patients with HER2 mutated had worse PFS for PD-1 antibody than those without.