Chen Lingli, Xu Lei, Shen Licheng, Luo Rongkui, Jiang Dongxian, Wang Yueqi, Li Wei, Hou Yingyong
Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Front Genet. 2022 Feb 4;12:831318. doi: 10.3389/fgene.2021.831318. eCollection 2021.
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 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 ( = 0.354). However, in stage III, the mortality rate in the HER2-positive group was reduced ( = 0.005) and that in stage IV was higher ( = 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.
胆囊癌（GBC）占胆道恶性肿瘤的80%-95%，预后不良。人表皮生长因子受体2（HER2）是GBC一个有前景的治疗靶点。通过免疫组织化学（IHC）和荧光原位杂交（FISH）方法，在306例GBC病例所构建的高通量组织芯片（TMA）上鉴定HER2表达和基因扩增情况，以研究其与GBC及临床病理特征的关系。腺癌占病例的223例（72.9%），其中62例（27.8%）为乳头状腺癌或具有部分乳头状结构。腺癌患者中16.1%（36/223）和具有乳头状结构的腺癌患者中41.9%（26/62）检测到HER2阳性。对143例接受根治性切除的原发性GBC病例且有24例HER2阳性肿瘤患者的生存数据进行分析，结果有效；中位生存时间未达到，5年生存率为52.9%。0-I期的所有患者均存活，HER2阳性组和II期HER2阴性组的结果相似（P = 0.354）。然而，在III期，HER2阳性组的死亡率降低（P = 0.005），而在IV期则更高（P = 0.005）。总之，乳头状GBC患者中HER2阳性率显著更高。HER2的预测价值因临床分期而异，早期无预测价值，III期较好，IV期较差。
