A large cohort of consecutive patients confirmed frequent HER2 positivity in gastric carcinomas with advanced stages.

Abstract:

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.

journal_name

Ann Surg Oncol

authors

Cho J,Jeong J,Sung J,Sung CO,Kim KM,Park CK,Choi MG,Sohn TS,Bae JM,Kim S

doi

10.1245/s10434-012-2818-0

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

S477-84

eissn

1068-9265

issn

1534-4681

journal_volume

20 Suppl 3

pub_type

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