Identification of the Coexisting HER2 Gene Amplification and Novel Mutations in the HER2 Protein-Overexpressed Mucinous Epithelial Ovarian Cancer
| Autor: | Jeng-Dong Hsu, Ming-Yung Lee, Wu-Hsien Kuo, Yeu-Sheng Tyan, Hung Chiang, Wea-Lung Lin, Alexandra Ruan, Fong-Lin Chen, Chih-Ping Han |
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| Rok vydání: | 2011 |
| Předmět: |
endocrine system diseases
Receptor ErbB-2 Biology Polymerase Chain Reaction Immunoenzyme Techniques Germline mutation Surgical oncology Humans Epithelial ovarian cancer skin and connective tissue diseases Gene In Situ Hybridization Fluorescence Ovarian Neoplasms Gene Amplification DNA Neoplasm Prognosis Adenocarcinoma Mucinous Molecular biology female genital diseases and pregnancy complications Cystadenocarcinoma Serous Endometrial Neoplasms Survival Rate Oncology Mutation HER2 Gene Amplification Cancer research Female Surgery Adenocarcinoma Clear Cell |
| Zdroj: | Annals of Surgical Oncology. 18:2388-2394 |
| ISSN: | 1534-4681 1068-9265 |
| DOI: | 10.1245/s10434-011-1572-z |
| Popis: | Although overexpression, amplification, and somatic mutation of the HER2 gene have been noted in various types of human cancers, we report here for the first time that novel mutations and amplification of the HER2 gene occurred concomitantly in mucinous epithelial ovarian cancer (EOC).Twenty-seven tissue microarray samples from EOC patients were analyzed by immunohistochemistry (IHC) with Dako c-erb-B2 antibody and subsequently were examined by fluorescence in situ hybridization (FISH) with the Abbott PathVysion HER2 DNA Probe Kit. HER2 gene, exon 18-24, encoding a tyrosine kinase domain, was analyzed by polymerase chain reaction (PCR) and direct sequencing.The FISH-IHC paired results confirmed 19 concordant negative results and 3 concordant positive results. Moreover, all 4 HER2-amplified cases were of the mucinous type, whereas the remaining 23 HER2-nonamplified cases were of the nonmucinous type. The 4 mucinous EOC cases with HER2 gene amplification were selected and further analyzed for HER2 gene mutations. Data revealed that somatic mutations were present in 2 cases (R970W and E971G), but absent in the other 2 cases.HER2 protein overexpression correlated significantly with HER2 gene amplification in EOC (P = 0.027). It is surprising that all 4 cases of mucinous EOC showed HER2 gene amplification confirmed by FISH testing. However, we suppose that increasing the number of cases would possibly modify the results. This study also showed that both HER2 gene amplification and somatic mutations are not mutually exclusive in mucinous EOC. Further studies are warranted to investigate the potential role of anti-HER2 therapy. |
| Databáze: | OpenAIRE |
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