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A Large Cohort of Consecutive Patients Confirmed Frequent HER2 Positivity in Gastric Carcinomas with Advanced Stages.
MedLine Citation:
PMID:  23274580     Owner:  NLM     Status:  Publisher    
BACKGROUND: Trastuzumab in association with systemic cytotoxic chemotherapy is the standard of care for patients with advanced HER2-positive gastric carcinoma (GC). However, HER2 as a prognostic factor in GC remains controversial. METHODS: HER2 overexpression and amplification was evaluated by immunohistochemistry (IHC) and silver in situ hybridization (SISH) in 2,798 GCs obtained from 2,727 gastrectomy and 71 open/laparoscopic biopsy specimens from patients with peritoneal seeding. Regional heterogeneity was defined as the proportion of tumor cells showing membranous staining in 10-70 % of tumor cells. Genetic heterogeneity was determined by the existence of HER2/CEP17 ratio higher than 2.0 in >5 to <50 % of tumor cells. RESULTS: In IHC, 184 cases (6.6 %) were 3+ and 44 cases (1.6 %) were 2+. Of 44 HER2 2+ cases, SISH showed HER2 gene amplification in 21 cases (47.7 %), chromosome 17 polysomy in six cases (13.6 %), and genetic heterogeneity in five cases (11.4 %). HER2 positivity found in 7.3 % of GCs was significantly associated with older age, male gender, intestinal histology, upper third in location, higher lymph node stage (p < .002), and advanced AJCC stage (p = .033). Regional heterogeneity of HER2 was closely associated with 2+ (70.5 vs 42.9 % in 3+, p = .001) and diffuse or mixed histologic type (p = .005). CONCLUSIONS: Regional heterogeneity of HER2 expression was closely associated with weak HER2 overexpression (2+) and with diffuse or mixed histology. Polysomy of chromosome 17 would be an important cause of HER2 2+ in IHC. Frequent HER2 positivity observed in GCs with advanced stages suggests that HER2 may be involved in tumor progression and poor prognosis.
Junhun Cho; Jiyun Jeong; Jiyoun Sung; Chang Ohk Sung; Kyoung-Mee Kim; Cheol Keun Park; Min Gew Choi; Tae Sung Sohn; Jae Moon Bae; Sung Kim
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-30
Journal Detail:
Title:  Annals of surgical oncology     Volume:  -     ISSN:  1534-4681     ISO Abbreviation:  Ann. Surg. Oncol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9420840     Medline TA:  Ann Surg Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
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