Evaluation of HER-2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction.
HER-2 gene amplification and the overexpression of HER-2 protein have been observed in various solid tumors, including gastric carcinomas. HER-2 gene amplification has attracted research attention since the development of the new therapeutic agent trastuzumab. Here, we evaluated HER-2 status in the surgically resected tissues of 248 gastric carcinoma cases using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and real-time quantitative polymerase chain reaction (q-PCR) and compared the results. In addition, we compared clinicopathologic characteristics with the presence of HER-2 gene amplification and with protein overexpression. Among the 248 cases, 56 (22.6%) cases showed HER-2 overexpression (2+ or 3+) by IHC and 19 cases (7.7%) showed HER-2 gene amplification by FISH. Four (2.1%) of the 192 cases negative (0 or 1+) by IHC showed amplification by FISH, whereas 15 (26.8%) of the 56 cases with HER-2 protein overexpression showed HER-2 amplification by FISH. The correlation between IHC and FISH results was statistically significant (P < .001). HER-2 protein overexpression and HER-2 gene amplification were common in cases with a well- or moderately differentiated histology according to the World Health Organization classification (P < .001) and in cases of intestinal type by the Lauren classification (P < .001). Real-time q-PCR results showed that calculated HER-2/GAPDH ratios were higher in amplified cases with 100.0% sensitivity and 96.9% specificity using FISH results as the standard. Measurements of HER-2 expression by FISH and real-time q-PCR and of HER-2 protein by IHC were found to be highly concordant at determining HER-2 status in gastric carcinoma.
Kim
Min A
MA
Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Jung
Eun Ji
EJ
Lee
Hye Seung
HS
Lee
Hee Eun
HE
Jeon
Yoon Kyung
YK
Yang
Han-Kwang
HK
Kim
Woo Ho
WH
D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016133:Polymerase Chain Reaction / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D013274:Stomach Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases