Laboissiere Renato Santos, Buzelin Marcelo Araújo, Balabram Débora, De Brot Marina, Nunes Cristiana Buzelin, Rocha Rafael Malagoli, Cabral Mônica Maria Demas Álvares, Gobbi Helenice
Departamento de Medicina DEMED-UFSJ, Campus Dom Bosco. Praça Dom Helvécio, 74. Fábricas, São João del-Rei, MG, 36301-160, Brazil.
Departamento de Anatomia Patológica FM-UFMG, Avenida Prof. Alfredo Balena, 190 - 3o. andar, Belo Horizonte, MG, 30130-100, Brazil.
BMC Gastroenterol. 2015 Nov 4;15:157. doi: 10.1186/s12876-015-0384-1.
Gastric cancer is usually diagnosed in an advanced stage of disease and treatment options are sparse. Trastuzumab was recently approved for metastatic or locally advanced carcinomas arising in the stomach or in the gastroesophageal junction in patients with HER2-positive tumors. However, data on the frequency of HER2-positive cases among Brazilian patients are limited. Our aim was to characterize HER2 protein and gene status in a series of Brazilian patients with gastric cancer and to evaluate its association with clinicopathological data.
Histological slides from 124 primary gastrectomies were reviewed and their pathological reports were retrieved from the files at a Brazilian university hospital. Automated immunohistochemistry for HER2 was performed on whole-tissue sections from each tumor. HER2-equivocal cases by immunohistochemistry were submitted to automated dual in situ hybridization for gene amplification evaluation. HER2 status was confronted with clinicopathological parameters in order to assess statistically significant associations.
Immunohistochemistry analysis revealed that 13/124 cases (10.5 %) were HER2 positive (3+), 10/124 cases (8.1 %) were equivocal (2+) and 101/124 cases (81.4 %) were negative, being 7 cases 1+. None of the equivocal cases showed gene amplification. The overall HER2 positivity rate was 10.5 %. There was an association between HER2 expression and Laurén's intestinal histological subtype (P = 0.048), well to moderately differentiated tumors (P = 0.004) and presence of lymphovascular invasion (P = 0.031). No association was found between HER2 status and tumor topography.
Confronted with data published by other authors, the lower percentage of HER2-positive cases found in our series might be partially explained by the lower frequency of tumors arising at the gastroesophageal junction in comparison with distal gastric carcinomas in Brazilian patients. This could also account for the lack of statistically significant association between HER2 status and tumor topography in our study.
胃癌通常在疾病晚期被诊断出来，治疗选择有限。曲妥珠单抗最近被批准用于治疗HER2阳性肿瘤的胃或胃食管交界部位的转移性或局部晚期癌。然而，巴西患者中HER2阳性病例的频率数据有限。我们的目的是对一系列巴西胃癌患者的HER2蛋白和基因状态进行特征分析，并评估其与临床病理数据的关联。
回顾了124例原发性胃切除术的组织学切片，并从巴西一家大学医院的档案中检索了它们的病理报告。对每个肿瘤的全组织切片进行HER2的自动免疫组织化学检测。免疫组织化学结果不明确的病例进行自动双重原位杂交以评估基因扩增情况。将HER2状态与临床病理参数进行对比，以评估统计学上的显著关联。
免疫组织化学分析显示，124例中有13例（10.5%）HER2阳性（3+），10例（8.1%）结果不明确（2+），101例（81.4%）为阴性，7例为1+。没有一例结果不明确的病例显示基因扩增。HER2总体阳性率为10.5%。HER2表达与劳伦氏肠型组织学亚型（P = 0.048）、高分化至中分化肿瘤（P = 0.004）以及淋巴管浸润的存在（P = 0.031）之间存在关联。未发现HER2状态与肿瘤部位之间存在关联。
与其他作者发表的数据相比，我们系列研究中HER2阳性病例的比例较低，部分原因可能是与巴西患者的远端胃癌相比，胃食管交界部位肿瘤的发生率较低。这也可以解释我们的研究中HER2状态与肿瘤部位之间缺乏统计学上的显著关联。
