Abstract
Gallbladder carcinoma (GBC) is responsible for 80%–95% of biliary tract malignancies and has a dismal prognosis. Human epidermal growth factor receptor 2 (HER2) is a promising therapeutic target of GBC. Through immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods, HER2 expression and gene amplification were identified on high-output tissue microarrays (TMAs) developed in 306 GBC cases to investigate its relationship with GBC and clinicopathological characteristics. Adenocarcinomas accounted for 223 (72.9%) of the cases, with 62 (27.8%) being papillary adenocarcinoma or having partial papillary structure. HER2 positivity was studied in 16.1% (36/223) of patients with adenocarcinoma and 41.9% (26/62) in adenocarcinoma with papillary structures. For 143 radically resected primary GBC cases with 24 HER2-positive tumors, survival data were valid; the median survival time was not reached, and the 5-year survival rate was 52.9%. All patients in stages 0–I survived, and the results of the HER2-positive group and the stage II HER2-negative group were similar (p = 0.354). However, in stage III, the mortality rate in the HER2-positive group was reduced (p = 0.005) and that in stage IV was higher (p = 0.005). In conclusion, HER2 positivity was significantly higher in patients with papillary GBC. The predictive value of HER2 varies by clinical stage, with no prediction in the early stages, better in stage III, and worse in stage IV.
Highlights
Human epidermal growth factor receptor 2 (HER2), alias Neu or ErbB2, is an important oncogene that has an essential function in cell proliferation and dedifferentiation (Yarden and Sliwkowski, 2001) and has been extensively studied in breast (Slamon et al, 2001; Slamon et al, 2011), gastric (Bang et al, 2010), and colon cancer (El-Deiry et al, 2015)
HER2 status was evaluated in Gallbladder carcinoma (GBC) and its prognostic value assessed
The HER2 status in GBC showed considerable heterogeneity, and the frequency of HER2 positivity varied from 0% to 25% in different studies (Albrecht et al, 2020; Matsuyama et al, 2004; Nakazawa et al, 2005; Chaube et al, 2006; Kawamoto et al, 2007; Puhalla et al, 2007; Harder et al, 2009; Shafizadeh et al, 2010; Kumari et al, 2012; Toledo et al, 2012; Roa et al, 2014; Moy et al, 2015; Yoshida et al, 2016)
Summary
Human epidermal growth factor receptor 2 (HER2), alias Neu or ErbB2, is an important oncogene that has an essential function in cell proliferation and dedifferentiation (Yarden and Sliwkowski, 2001) and has been extensively studied in breast (Slamon et al, 2001; Slamon et al, 2011), gastric (Bang et al, 2010), and colon cancer (El-Deiry et al, 2015). Chemotherapy plus the anti-HER2 antibody trastuzumab is the recommended first-line therapy (Muro et al, 2019) based on the HER2 Positivity in Gallbladder Carcinoma randomized, multicenter, phase 3 ToGA (Trastuzumab for Gastric Cancer) trial, in which the overall survival (OS) was significantly longer with chemotherapy plus trastuzumab than with chemotherapy alone (Bang et al, 2010). Since most cases are in the advanced stage, GBC often leads to a poor prognosis and a less than 1year median survival rate (Lazcano-Ponce et al, 2001). Even with the current first-line standard-of-care treatment (gemcitabine–cisplatin) for advanced GBCs, the median OS is less than 1 year (Valle et al, 2014). The study included seven biliary cancers/GBCs, and the objective response rate was 29% (2/7) (95% CI = 4–71). HER2 status in GBC shows considerable heterogeneity, and the frequency of the HER2-positive ratio varies from 0% to 31.3% in different studies (Albrecht et al, 2020; Hiraoka et al, 2020)
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