胆囊腺癌HER2阳性表达的临床意义

Clinical significance of HER2 positivity in gallbladder adenocarcinoma

目的探讨胆囊腺癌HER2阳性表达的临床意义及免疫组织化学（IHC）评分标准。方法对123例胆囊腺癌切除标本进行HER2IHC染色，按胃癌HER2IHC评分标准评分，对IHC评分2＋及3＋病例行HER2双探针荧光原位杂交（FISH）检测。并将HER2阳性结果与胆囊腺癌临床病理特征进行比较。结果123例胆囊腺癌中检出HER2基因扩增27例，检出率为22．0％。IHC评分结果分别为12例2＋，24例3＋；其中FISH扩增阳性者分别为5例和22例（5／12和91．7％，22／24）。IHC染色的异质性明显。3例细胞膜完整强着色但着色细胞数量〈10％的病例中有1例显示HER2基因扩增。HER2基因扩增在高、中、低分化肿瘤间差异具有统计学意义（x^2=24．4，P〈0．01），并与组织分化程度相关（C=0．45）。结论大约20％左右的胆囊腺癌存在HER2基因扩增，为这部分患者开展靶向治疗研究奠定了基础。胃癌HER2IHC评分标准适用于胆囊腺癌，但细胞膜完整强着色且着色细胞数量〈10％的病例应该列入IHC评分2＋组，并进一步行FISH检测。

Objective To study the clinical significance of HER2 overexpression and/or amplification in gallbladder adenocarcinoma. Methods HER2 staining was performed on 123 cases of gallbladder adenocarcinoma specimens by IHC using scoring criteria for gastric cancer. FISH test was performed on the IHC score 2 ＋ and 3 ＋ cases and the results were correlated with clinicopathological findings. Results In total of 123 cases of gallbladder adenocarcinomas, HER2 amplification detection rate was 22. 0% （27/123）. Among 27 cases with HER2 gene amplification, 5 cases were IHC 2＋ （5/12） and 22 cases were IHC 3＋ （91.7%,22/24）, and the concordance rates between IHC and FISH were 41.7%and 91.7% respectively. The heterogeneity of HER2 expression was observed in 3 cases with complete strong cell membrane staining but the number of stained cells of〈 10%. Among them, 1 case showed HER2 gene amplification. The difference of HER2 gene amplification in well, moderately and lowly differentiated tumors has statistical significance（X^2= 24.4, P〈0. 01 ）, and its detection rate was related to the degree of tumor differentiation （C= 0.45）. Conclusions About 20% gallbladder adenocarcinomas have HER2 positivity, providing the targeted therapy implicationfor these patients. IHC HER2 scoring system for gastric carcinoma is suitable for gallbladder carcinoma. However, the cases with complete strong membrane staining but in 〈 10% tumor ceils should be included in the 2＋ score IHC group.