胃癌原发灶不同区域HER2的表达及其临床意义

Detection of HER2 expression in different locations of surgical specimens in patients with primary gastric cancer

目的探讨胃癌手术标本不同区域人类表皮生长因子受体2(HER2)的异质性及其临床意义,分析原发灶HER2表达与胃癌临床病理特征的关系。方法收集2004至2012年胃癌根治手术标本70例,采用免疫组织化学(IHC)对每例胃癌3个不同区域的组织蜡块进行HER2蛋白表达检测,利用荧光原位杂交(FISH)检测HER2蛋白为2+的所有组织蜡块,参照2011年版的《胃癌HER2检测指南》中的判读标准将检测结果进行比较。结果 70例胃癌手术标本3个不同区域HER2有差异表达11例(4例1+,4例2+,3例3+),无差异表达59例(56例0,1例2+,2例3+),结合FISH1检测结果,HER2表达分别为63.6%(7★1)与5.1%(3/59),两者比较差异有统计学意义(P<0.05);胃癌HER2表达与肿瘤Lauren分型及分化程度有关(均P<0.05)。结论胃癌原发灶不同区域HER2表达存在明显异质性,多区域取材检测有助于全面可靠评估HER2表达,对于FISH检测无基因扩增的HER2蛋白为2+的患者应选取肿瘤其他部位再次进行FISH检测。

Objective To investigate the heterogeneity of HER2 detection in different location of surgical specimens in patients with gastric cancer and its clinical significance. Methods Seventy surgical specimens of gastric cancer were collect- ed from 2004 to 2012. The expression of HER2 protein was examined by immunohistochemistry （IHC） in 3 blocks taken from dif- ferent location of each specimens. Samples with HER2 protein 2＋ were also examined by fluorescence in situ hybridization （FISH）. Results of HER2 status were evaluated according to Gastric Cancer HER2 Testing Guidelines（2011 edition）. Results IHC showed that HER2 was expressed differently in different locations in 11 cases and not differently in 59 were not differentially ex- pressed （HER2 immunoreaction scorings of 0, 2＋, and 3＋ were present in 56, 1 and 2 cases. Combined with FISH results, the positive HER2 rate was 63.6% （7/11） and 5.1% （3/59）. There was a significant difference between the positive rates（P〈0.05）. The positive rate of HER2 was significantly associated with Lauren type and degree of differentiation （P〈0.05）. Conclusion The de- tection of HER2 expression showed significant heterogeneity in different locations of primary gastric cancer, and multi-region de- tection contributed to comprehensive and reliable assessment of HER2 status. The samples with non-gene amplification in FISH test and HER2 protein 2＋ should be subject to another FISH test using specimens in different locations.