Clinicopathological and prognostic significance of HER2 status in surgically resected colorectal liver metastases

Background The clinicopathological and prognostic significance of human epidermal growth factor receptor 2 (HER2) status in surgically resected colorectal liver metastases (CRLM) remains uncertain. Methods HER2 expression was evaluated by immunohistochemical (IHC) in two CRLM tissue microarrays (TMAs). For samples with an IHC score of 2+ or 3+, fluorescence in situ hybridization (FISH) was performed to assess HER2 amplification. The association of HER2 amplification with clinicopathological parameters and prognosis was assessed using Fisher's exact test and Kaplan-Meier method, respectively. Results HER2 expression was consistent between primary tumor and liver metastases in 66.9% (85/127) cases (r = 0.643, p = 0.001). After FISH validation, HER2 amplification was identified in 6.25% (13/208) patients. HER2 amplification was significantly associated with age (p = 0.017), bilobar involvement (p = 0.005) and left-sided RAS/RAF wild-type status (p = 0.002). In the overall cohort, HER2 amplification was correlated with significantly worse relapse-free survival (RFS). Further stratification revealed that among left-sided RAS/RAF wild-type cases, HER2 amplification was significantly associated with worse overall survival (OS) (30.2 vs. 50.9 months, p = 0.040) and RFS (5.77 vs. 19.97 months, p = 0.017). Conclusion HER2 amplification is more enriched in CRLMs with younger age, left-sided RAS/RAF wild-type, and bilobar involvement. Moreover, HER2 amplification predicts a poorer prognosis especially in left-sided RAS/RAF wild-type CRLMs.