The long term goal of this study is development of surrogate molecular markers for early detection of micrometastatic stomach cancer. Gastric adenocarcinoma is the second leading cause of cancer-related death in the world. With a U.S. prevalence rate of 5-7 cases per 100,000 population and 20,000 new cases per year, gastric cancer nonetheless accounts for 3% of all U.S. cancer deaths. Gastric neoplasms are predominantly (95%) adenocarcinomas which are rarely diagnosed in their early stages. At diagnosis, 25% of patients have disease confined to the stomach, 50% show locoregional lymph node metastases and extragastric spread, and 25% have distant metastases. Those patients presenting with cancer confined to the stomach are candidates for curative gastric resection. Unfortunately, about 70% of these patients die from disease relapse within 5 years of surgery. Early detection of gastric micrometastases is thus a major clinical challenge. The hypothesis driving the proposed study is that gastric epithelial cell-specific genes expressed in ectopic gastric tumor cells in lymph nodes are molecular markers for early detection of metastatic gastric cancers. Our preliminary data indicate that quantitative real-time RT-PCR readily detects expression of several mRNA transcripts in human gastric biopsies and in human gastric adenocarcinoma cells. Based on these and related RT-PCR data measuring expression of lung cancer-associated mRNAs in mediastinal lymph nodes, we propose two specific aims: 1) To identify a panel of RT-PCR primer pairs for quantitative detection of genes that may be over-expressed in malignant lymph nodes of gastric cancer patients, and 2) To establish criteria for interpretation of marker gene RT-PCR data by screening lymph node aspirates from gastric cancer patients. We anticipate that the proposed study will establish criteria for interpretation of RT-PCR data from lymph node cells acquired by endoscopic ultrasonographic-fine needle aspiration, and will serve as the basis for prospective evaluation of quantitative real-time RT-PCR and its correlation with clinical outcome in a more comprehensive cohort of patients. The successful development and validation of a lymph node RT-PCR-based assay for micrometastatic stomach cancer is likely to have a significant clinical impact.
