Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada M5S 1A8.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada M5S 1A8; Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada M4N 3M5.
Hum Pathol. 2014 May;45(5):970-5. doi: 10.1016/j.humpath.2013.12.010. Epub 2014 Jan 8.
In advanced gastric and gastroesophageal junction (GEJ) adenocarcinomas that overexpress human epidermal growth factor receptor 2 (HER2), treatment with trastuzumab confers a survival benefit. To select patients for treatment, HER2 status is evaluated by immunohistochemistry (IHC) and in situ hybridization. Gastric and GEJ adenocarcinomas demonstrate heterogeneity in HER2 expression. Nonetheless, testing is often performed on biopsies alone, which raises the issue of nonrepresentative sampling. We investigated the correlation of HER2 status between matched biopsy and resection specimens and the role of tumor heterogeneity in contributing to discrepancy. A total of 128 patients with gastric or GEJ adenocarcinoma had tissue available from a biopsy and subsequent resection. HER2 IHC was performed and evaluated by the criteria used in the Trastuzumab for Gastric Cancer clinical trial. In situ hybridization was performed if IHC was equivocal (2+) in either the biopsy or resection and in discrepant cases. Tumor heterogeneity was defined as 3+ or 2+ staining in 10% to 60% of tumor cells. Overall, HER2 was overexpressed in 18 tumors (14%), with a biopsy-resection concordance of 96.1%. Five cases were discrepant; 2 were positive on biopsy only, and 3 were positive on resection only. Tumor heterogeneity was seen in 80% of discrepant biopsies and resections, compared with 24% of concordant cases (P = .016). Our study demonstrates strong concordance between biopsy and resection specimens for HER2 overexpression in gastric cancer. Discordance was correlated with tumor heterogeneity. Overall, both biopsy and resection specimens are appropriate for HER2 testing, but generous sampling for biopsy specimens is necessary to ensure accurate assessment.
在人表皮生长因子受体 2（HER2）过表达的晚期胃和胃食管交界处（GEJ）腺癌中，曲妥珠单抗治疗可带来生存获益。为了选择接受治疗的患者，通过免疫组织化学（IHC）和原位杂交来评估 HER2 状态。胃和 GEJ 腺癌的 HER2 表达存在异质性。尽管如此，检测通常仅在活检标本上进行，这就带来了代表性采样不足的问题。我们研究了匹配的活检和切除标本之间的 HER2 状态相关性，以及肿瘤异质性在导致差异方面的作用。共有 128 例胃或 GEJ 腺癌患者的活检和随后的切除标本均有组织学样本。进行了 HER2 IHC 检测，并根据曲妥珠单抗治疗胃癌临床试验中使用的标准进行了评估。如果活检或切除标本的 IHC 结果为不确定（2+），或者结果不一致，则进行原位杂交。肿瘤异质性定义为 10%至 60%的肿瘤细胞中存在 3+或 2+染色。总体而言，18 例肿瘤（14%）HER2 过表达，活检与切除标本的一致性为 96.1%。有 5 例结果不一致，其中 2 例仅在活检标本中呈阳性，3 例仅在切除标本中呈阳性。与一致性病例（24%）相比，80%不一致的活检和切除标本中存在肿瘤异质性（P =.016）。我们的研究表明，胃癌中 HER2 过表达在活检和切除标本之间具有很强的一致性。不一致与肿瘤异质性相关。总体而言，活检和切除标本均适合进行 HER2 检测，但为了确保准确评估，活检标本需要进行大量采样。
