PMID- 21347793
OWN - NLM
STAT- MEDLINE
DCOM- 20111207
LR  - 20141120
IS  - 1534-4681 (Electronic)
IS  - 1068-9265 (Linking)
VI  - 18
IP  - 8
DP  - 2011 Aug
TI  - Identification of the coexisting HER2 gene amplification and novel mutations in 
      the HER2 protein-overexpressed mucinous epithelial ovarian cancer.
PG  - 2388-94
LID - 10.1245/s10434-011-1572-z [doi]
AB  - 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.
FAU - Lin, Wea-Lung
AU  - Lin WL
AD  - Department of Pathology, Chung-Shan Medical University Hospital and School of 
      Medicine, Chung-Shan Medical University, Taichung, Taiwan.
FAU - Kuo, Wu-Hsien
AU  - Kuo WH
FAU - Chen, Fong-Lin
AU  - Chen FL
FAU - Lee, Ming-Yung
AU  - Lee MY
FAU - Ruan, Alexandra
AU  - Ruan A
FAU - Tyan, Yeu-Sheng
AU  - Tyan YS
FAU - Hsu, Jeng-Dong
AU  - Hsu JD
FAU - Chiang, Hung
AU  - Chiang H
FAU - Han, Chih-Ping
AU  - Han CP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110223
PL  - United States
TA  - Ann Surg Oncol
JT  - Annals of surgical oncology
JID - 9420840
RN  - 0 (DNA, Neoplasm)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adenocarcinoma, Clear Cell/genetics/metabolism/pathology
MH  - Adenocarcinoma, Mucinous/genetics/metabolism/pathology
MH  - Cystadenocarcinoma, Serous/genetics/metabolism/pathology
MH  - DNA, Neoplasm/genetics
MH  - Endometrial Neoplasms/genetics/metabolism/pathology
MH  - Female
MH  - *Gene Amplification
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization, Fluorescence
MH  - Mutation/*genetics
MH  - Ovarian Neoplasms/*genetics/*metabolism/pathology
MH  - Polymerase Chain Reaction
MH  - Prognosis
MH  - Receptor, ErbB-2/*genetics/*metabolism
MH  - Survival Rate
EDAT- 2011/02/25 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/02/25 06:00
PHST- 2010/10/07 00:00 [received]
PHST- 2011/02/25 06:00 [entrez]
PHST- 2011/02/25 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - 10.1245/s10434-011-1572-z [doi]
PST - ppublish
SO  - Ann Surg Oncol. 2011 Aug;18(8):2388-94. doi: 10.1245/s10434-011-1572-z. Epub 2011 
      Feb 23.