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01.08.2011 | Translational Research and Biomarkers | Ausgabe 8/2011

Annals of Surgical Oncology 8/2011

Identification of the Coexisting HER2 Gene Amplification and Novel Mutations in the HER2 Protein-Overexpressed Mucinous Epithelial Ovarian Cancer

Zeitschrift:
Annals of Surgical Oncology > Ausgabe 8/2011
Autoren:
MS, DDS Wea-Lung Lin, MD, PhD Wu-Hsien Kuo, MD, PhD Fong-Lin Chen, PhD Ming-Yung Lee, Alexandra Ruan, MD, PhD Yeu-Sheng Tyan, MS, DDS Jeng-Dong Hsu, MD Hung Chiang, MD, PhD Chih-Ping Han
Wichtige Hinweise
Epithelial ovarian cancer (EOC); Immunohistochemistry (IHC); Fluorescence in situ hybridization (FISH); Polymerase chain reaction (PCR); American Society of Clinical Oncology and the College of American Pathologists (ASCO-CAP)

Abstract

Background

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).

Methods

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.

Results

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.

Conclusions

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.

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