위샘암종에서 HER2 유전자의 변이 빈도: 면역조직화학염색과 자동화 은제자리부합법 및 형광제자리부합법과의 비교
HER2 Status in Gastric Adenocarcinomas Assessed by Immunohistochemistry, Automated Silver-Enhanced In Situ Hybridization and Fluorescence In Situ Hybridization
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Background : Recently, many studies have focused on human epidermal growth factor receptor 2 (HER2) status in gastric cancer due to HER2-targeted therapy using trastuzumab. We investigated HER2 overexpression and amplification and their concordance rate in Korean gastric adenocarcinomas. Methods : Tissue microarrays were constructed with 232 gastric adenocarcinoma samples. We performed immunohistochemistry (IHC), silver-enhanced in situ hybridization (SISH) and fluorescence in situ hybridization (FISH) for HER2. Results : IHC was negative in 94.8% (218/232), equivocal in 1.7% (4/232) and positive in 3.5% (8/232) of cases. HER2 protein expression was heterogeneous in 75% (9/12) of IHC 2+/3+ cancers. Gene amplification was observed in 6.5% (15/230) by SISH and the same 15 cases were also FISH-positive. We observed HER2 amplification in 1.4%, 27.3%, 25%, and 100% of IHC 0, 1+, 2+, and 3+ gastric adenocarcinomas, respectively. The concordance rate between IHC and SISH results was 95.7%. Conclusions : HER2 overexpression and amplification were less frequent in gastric adenocarcinomas than breast carcinomas. Compared to breast carcinoma, (1) there may be IHC-negative but gene amplification-positive cases for HER2 and (2) frequent intratumoral heterogeneity of IHC for HER2 in gastric adenocarcinomas.
Abstract
Background : Recently, many studies have focused on human epidermal growth factor receptor 2 (HER2) status in gastric cancer due to HER2-targeted therapy using trastuzumab. We investigated HER2 overexpression and amplification and their concordance rate in Korean gastric adenocarcinomas. Methods : Tissue microarrays were constructed with 232 gastric adenocarcinoma samples. We performed immunohistochemistry (IHC), silver-enhanced in situ hybridization (SISH) and fluorescence in situ hybridization (FISH) for HER2. Results : IHC was negative in 94.8% (218/232), equivocal in 1.7% (4/232) and positive in 3.5% (8/232) of cases. HER2 protein expression was heterogeneous in 75% (9/12) of IHC 2+/3+ cancers. Gene amplification was observed in 6.5% (15/230) by SISH and the same 15 cases were also FISH-positive. We observed HER2 amplification in 1.4%, 27.3%, 25%, and 100% of IHC 0, 1+, 2+, and 3+ gastric adenocarcinomas, respectively. The concordance rate between IHC and SISH results was 95.7%. Conclusions : HER2 overexpression and amplification were less frequent in gastric adenocarcinomas than breast carcinomas. Compared to breast carcinoma, (1) there may be IHC-negative but gene amplification-positive cases for HER2 and (2) frequent intratumoral heterogeneity of IHC for HER2 in gastric adenocarcinomas.
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