HER2 status based on breast cancer guidelines as a useful prognostic marker of T2 gallbladder cancer

T2 gallbladder cancer (GBC) is the only stage showing a survival benefit after complete surgical resection, but recurrence rates remain high. Although human epidermal growth factor receptor 2 (HER2) has emerged as a therapeutic target, its role in T2 GBC remains unclear. This study investigated the status and prognostic impact of HER2 expression on T2 GBC.

HER2 expression and amplification were detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively, in 90 patients with T2 GBC who underwent radical cholecystectomy. We evaluated HER2 status according to the breast and gastric cancer guidelines and analyzed the effect of relevant prognostic factors on survival.

HER2 positive status was observed in 11.11% (10/90) and 8.89% (8/90) of cases based on gastric and breast cancer guidelines, respectively. Poor differentiation and a higher level of perineural invasion were independent prognostic factors of disease-free survival (DFS). Old age, male sex, presence of lymph node metastasis, poor differentiation, high levels of perineural invasion, and HER2 positivity based on breast cancer guidelines were identified as independent prognostic factors of overall survival (OS). Patients with HER2-positive T2 GBC according to breast cancer guidelines had worse OS.

HER2 positivity based on breast- but not gastric-cancer guidelines was associated with poorer survival. These results provide a criterion for the evaluation of HER2 and a rationale for therapeutic strategies targeting HER2 in T2 GBC.