Biomarkers in a Large Cohort of Gastric and GEJ Adenocarcinomas – Prevalence and Spectrum of Expression
Sandra Rost, Deborah Dunlap, Sara Chan, Susan Sa, Simonetta Mocci, Hartmut Koeppen. Genentech, South San Francisco, CA
Background: Gastric cancer is one of the most common causes of worldwide cancer-related death. The identification of biomarkers specific to gastric cancer is critical for the development of targeted therapies. Trastuzumab has been approved for the treatment of Her2-positive metastatic gastric cancer but there is no targeted therapy for patients with HER2-negative disease. An anti-Met antibody, onartuzumab, is being evaluated in patients with HER2-negative gastric cancer. We analyzed gastric and gastro-esophageal adenocarcinomas from 161 patients with various ethnic backgrounds for the expression of Her2, Met, PTEN, HGF, p53, ARID1A and FGFR2 to determine prevalence and potential overlap of these markers as well as differences in the expression pattern between different ethnic groups.
Design: Immunohistochemistry to determine expression of Her2, Met, PTEN, p53, beta-catenin and ARID1A was performed on paraffin sections. Expression of FGFR2 and HGF was evaluated by in-situ hybridization. Her2 expression was scored according to published guidelines. Expression of Met was scored based on intensity (negative to strong) and percent tumor cells positive with a 50% cutoff. PTEN was scored using an H-score with a range from 0 to 400; absence and decreased levels of PTEN were defined as H-scores of 0 and ≤ 100, respectively. Stains for p53 and ARID1A were evaluated for presence or absence of nuclear staining, respectively. ISH for FGFR2 and HGF was scored based on peak signal intensity in any area of the tumor.
Results: Her2-positive (IHC 3+) tumors accounted for 5% of all cases. Weak, moderate and strong expression of Met and FGFR2 were seen in 61, 7 and 2 and 22, 10 and 1% of cases, respectively; expression of these markers correlated with intestinal-type morphology (100% for Her2, 70% for Met and 66% for FGFR2). None of the Her2-positive cases showed strong expression of Met or FGFR2; two cases showed moderate expression of Met, one of which was also positive for FGFR2. Loss of or decreased PTEN were observed in 1% and 18% of cases, respectively. HGF RNA was observed in 23% (1+), 11% (2+) and 2% (3+) cases; expression was seen in stromal and/or malignant cells. 27% of cases showed staining for p53, loss of ARID1A staining was present in 10% of cases.
Conclusions: These data may guide the development of targeted therapies for gastric cancer. A significant proportion of Her2-negative patients express Met enabling clinical trials of Met inhibitors in this patient population. A detailed statistical analysis with respect to overlap of biomarkers and correlation with ethnicity will be described.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 98, Wednesday Afternoon