Prediction of lymph node metastasis and survival in patients with esophageal adenocarcinoma

This is a collaborative Study with Dr. James D. Luketich at the University of Pittsburgh Cancer institute.

This project is funded through 2010 by an R01 grant to Dr. Luketich from the NIH.

Summary: In the USA, the incidence of esophageal adenocarcinoma has risen more than 350% since 1974 while long-term survival rates have remained extremely poor (5-10%). As with most solid tumors, the identification of lymph node involvement and distant metastases are important determinants of prognosis and figure prominently in the clinical decision making process. Unfortunately, tumor spread to three distinct LN fields makes accurate nodal assessment of esophageal cancer difficult. Conventional imaging techniques are inaccurate for LN staging and even with radical lymph node dissection, patients with histologically negative lymph nodes have a 30-50% chance of developing recurrent disease, pointing out the limitations of current pathologic assessment and the TNM staging system. Our previously published reports, and ongoing research, indicate that disease recurrence and poor survival in these patients may be predicted by the presence of occult metastases to lymph nodes. Recently however, Beer et al. reported in Nature Medicine that gene expression in the primary site of lung adenocarcinomas can predict outcome in stage I (lymph node-negative) lung cancer patients 1 . In addition, Three other reports in Nature Genetics 2 , The Lancet 3 and Cancer Cell 4 demonstrate that the propensity to metastasize may actually be encoded in the gene expression patterns of primary tumors. Furthermore, the Lancet study by Huang et al. identified separate gene sets that seem to predict lymph node metastasis and overall recurrence in breast cancer patients. These interrelated events would thus appear to be the result of distinct biological processes that may be detected by analysis of the primary tumor.

It is our hypothesis that gene expression patterns in the primary tumor determine metastatic potential and probability of survival for patients with esophageal cancer. Subsequently, we believe that we will be able to identify sets of genes that correlate with both metastasis and survival. Given the correlation between lymph node status and survival in esophageal cancer, we also hypothesize that gene expression analysis and occult disease detection approaches may identify essentially the same sets of patients at high risk for recurrence. However, we are hopeful that the combination of these approaches will be more powerful than either approach alone for predicting overall outcome of esophageal cancer patients. If successful, this project has the potential to provide improved risk stratification of esophageal cancer patients and could eventually impact treatment decisions. In addition, we believe that this research will answer some very interesting questions about tumor biology and metastasis in esophageal adenocarcinoma.