Incidence and distribution of HER2-positive gastric and gastroesophageal junction (GEJ) adenocarinomas in British Columbia (BC).

Abstract

91 Background: HER2-positive rates have been reported as 20% of GC and 34% in GEJ adenocarcinoma in a recent global phase III trial with trastuzumab and chemotherapy. This study examines the incidence and distribution HER2-positive GC and GEJ adenocarcinomas in the province of BC. Methods: Formalin fixed embedded tissue from patients (pts) with resected gastric or GEJ adenocarcinoma from 2004-2007 were identified retrospectively through the BC Cancer Agency registry and prospectively for pts with a new diagnosis of advanced disease. Biopsies and resection samples were analyzed via previously validated methods IHC (Ventana 4B5 antibody), FISH (Eurovision probes) and SISH (Ventana probes). IHC scores of 3 were considered positive, 2 were cequivocal and 0 or 1 were negative. A 10% cut-off was used to determine positive samples. Equivocal staining was considered positive via FISH or SISH. A ratio of > 2.0 was considered amplified for FISH and SISH. P values were calculated using a logistic regression model with HER2 positive as the endpoint. Results: Of the 87 samples, 64 (74%) were gastric and 23 (26%) GEJ. Overall, HER2 was positive 20% (IHC), 18% (FISH) and 18% (SISH). 13% of cases tested IHC 3+ while 24% tested IHC 2+. In equivocal IHC 2+ cases, 7% were considered positive by FISH. Positivity rates were higher for GEJ (26%, 22% and 17%) vs. gastric (8%, 11% and 9%) via IHC (p = 0.02), but did not significantly differ by FISH (p = 0.19), or SISH (p = 0.30) respectively. The majority of positive cases were intestinal type vs. other (diffuse type or mixed) 25% vs. 0% IHC p = 0.0002, 25% vs. 3% FISH p = 0.001, 20% vs. 3% SISH p = 0.006. The positivity rates were similar with biopsy vs resection specimens (12% vs. 16% IHC p = 0.64, 12% vs. 21% FISH p = 0.30, 12% vs. 10%, SISH p = 0.88). Conclusions: The rates of HER2-positive disease in a Western population based study were similar to the ToGA study. HER 2 positivity was associated with cancers arising in the GEJ and of intestinal type. The frequency of positivity was similar for testing by biopsy versus resection specimens. This study is ongoing and updated results will be reported. No significant financial relationships to disclose.