Molecular predictors of treatment response in colon and gastric cancer.

Abstract

619 Background: With the noted exception of KRAS mutational status, currently there exists limited data regarding the incorporation of tumor-derived biomarkers in the clinical management of gastrointestinal malignancies. High ERCC1 levels have been associated with inferior results in platinum-treated patients with non-small cell lung cancer, esophageal cancers, and head and neck cancer. Lenz et al. concluded ERCC-1 gene expression levels may allow the selection of patients who may benefit from FOLFOX chemotherapy in metastatic colon cancer. Low intra-tumoral ERCC1 mRNA expression predicted improved PFS and OS in patients with esophageal adenocarcinoma who were treated with tri-modality therapy in the SWOG 0356 correlative study. Methods: To determine the prevalence and patterns of expression of select tumor biomarkers including ERCC1, TS, HER-2, KRAS, BRAF, and EGFR gene expression was measured in metastatic gastric and colorectal cancers using formalin fixed paraffin embedded tumor samples from 120 metastatic colorectal and 20 metastatic gastric cancer were dissected using laser-captured micro-dissection and analyzed for ERCC-1, TS, EGFR, RRM1, and VEGFR2a mRNA expression using a quantitative RT-PCR methodology. Gene expression values (relative mRNA levels) were recorded as ratios between the target gene and internal reference gene (beta-actin). A retrospective review of the patient’s response to therapy was planned. Results: In colorectal patients, the incidence of KRAS mutations was 50%, specifically Gly12Ser 4%, Gly12Val 11%, Gly12Asp 20%, Gly12 Cys 7% Gly12Ala 2% and Gly13Asp 8%. BRAF expression analysis displayed 91% wild type with 9% V600E mutations. Median expression values for ERCC1, TS, EGFR, RRM1, and VEGFR2A expression levels using RT-PCR were 1.23, 2.28, 1.90, 1.05, and 1.61 respectively in the colorectal subset. In gastric cancer, ERCC1, TS, and Her-2 median expression levels using RT-PCR were 1.54, 3.56, and 0.08 respectively. Correlation with clinical outcome is pending and will be reported later.