A Large Cohort of Consecutive Patients Confirmed Frequent HER2-Positivity in Gastric Carcinomas with Advanced Stages
Soomin Ahn, Junhun Cho, Cheol Keun Park, Sung Kim, Kyoung-Mee Kim. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
Background: Trastuzumab in association with systemic cytotoxic chemotherapy is the standard of care for patients with advanced HER2-positive gastric carcinoma (GC) and gastroesophageal (GE) junction cancer based on ToGA trial. However, the role of HER2 as a prognostic factor in GC remains controversial. This study was performed to investigate the clinicopathologic characteristics of HER2-positive GC in a large cohort of consecutive patients.
Design: HER2 overexpression/amplification was evaluated by immunohistochemistry (IHC) and silver in situ hybridization (SISH) in 2,798 GCs obtained from 2,727 total/subtotal gastrectomy specimens 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% to 70% of tumor cells in a representative block of surgical specimens. Genetic heterogeneity was determined by the existence of HER2/CEP17 ratio higher than 2.0 in 5–50% of the tumor cells.
Results: In IHC, 184 cases (6.6%) were 3+ and 44 cases (1.6%) were 2+. Out of 44 HER2 2+ cases, SISH showed HER2 gene amplification in 21 cases (47.7%), chromosome 17 polysomy in 6 cases (13.6%), and genetic heterogeneity in 5 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<0.002) and AJCC stage (p=0.033). Regional heterogeneity of HER2 expression was closely associated with 2+ (70.5% vs 42.9% in 3+, p=0.001) and diffuse or mixed histologic type (68.4% and 70.0% vs 43.1% in intestinal-type, p=0.005).
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.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 99, Wednesday Afternoon