HER2基因扩增和蛋白表达与胃癌临床病理特征和预后的关系

摘要

背景:曲妥珠单抗在人表皮生长因子受体2(HER2)阳性胃癌分子靶向治疗中的作用已得到确认,研究HER2评分与患者临床结局的关系可确定哪些患者可能从曲妥珠单抗治疗中获益.目的:探讨HER2基因扩增和蛋白表达与胃癌临床病理特征和预后的关系.方法:应用美国食品药品管理局(FDA)认证的检测试剂盒和Hofmann等报道的共识小组推荐胃癌HER2评分系统,采用荧光原位杂交(FISH)和免疫组化方法(IHC)检测177例胃癌组织的HER2基因扩增和蛋白表达.比较不同临床病理特征胃癌亚组间HER2阳性率的差异,以Kaplan-Meier生存曲线分析HER2与预后的关系.结果:177例胃癌组织中31例(17.5%)HER2阳性,肠型胃癌阳性率显著高于弥漫型/混合型胃癌(28.1%对12.5%,P=0.0109),分化较好的胃癌阳性率显著高于分化较差的胃癌(37.0%对10.7%,P＜0.0001).HER2与性别、年龄、肿瘤部位和TNM分期无关.HER2阳性与阴性者总体生存率无明显差异,但在分化较好的胃癌中,HER2阳性者预后差于HER2阴性者(P=0.0084).结论:肠型胃癌和分化较好的胃癌是曲妥珠单抗治疗的主要候选人群.HER2尚不能作为独立指标判断胃癌预后.%Background: The efficacy of trastuzumab for treating human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) has been confirmed by phase Ⅲ clinical trial. Investigation on correlation of HER2 score with clinical outcome will be helpful for determining which patient might be benefit from trastuzumab therapy. Aims: To study the correlation of HER2 gene amplification and protein expression with clinicopathological characteristics and prognosis of GC. Methods: One hundred and seventy-seven GC specimens were collected. HER2 gene amplification and protein expression were determined by using the Food and Drug Administration (FDA)-approved kits for fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), and were scored according to the consensus panel recommendations on HER2 scoring for GC. The difference in HER2 positivity rate among GC with different clinicopathological characteristics was analyzed, and the correlation between HER2 and prognosis was estimated by Kaplan-Meier survival curve. Results: Thirty-one cases of GC (17.5％) were positive for HER2. The positivity rates in intestinal type GC and well-differentiated GC were higher than those in diffuse/mixed type GC and poorly-differentiated GC, respectively (28.1％ vs. 12.5％, P=0.0109; 37.0％ vs. 10.7％, P＜0.0001), but were not correlated with gender, age, tumor location and TNM stage. The overall survival was not significantly different between HER2-positive and HER2-negative GC, but in welldifferentiated cases, the survival of HER2-positive GC was worse than that of HER2-negative GC (P = 0.0084). Conclusions: Patients with intestinal type GC and well-differentiated GC may be the potential responders to trastuzumab therapy. HER2 can not yet be served as an independent predictor for prognosis of GC.