In the USA, the incidence of esophageal adenocarcinoma has risen more than 350% since 1974 while long-term survival rates have remained at 10-15%. Current staging methods are inadequate for predicting survival in this disease, as evidenced by the fact that even patients with early stage, potentially resectable tumors frequently recur and die. Since treatment options are based on pathologic stage, clinicians need improved staging methods to assist in appropriate treatment planning for these patients. Our previously published reports indicate that disease recurrence and poor survival in esophageal cancer patients may be predicted, in part, by the presence of occult metastases to lymph nodes. Recently however, Beer et al. reported in Nature Medicine that gene expression patterns in primary tumors can predict outcome in stage I lung cancer patients. In addition, three new reports in Nature Genetics and The Lancet and Cancer Cell 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 can 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 adenocarcinoma. Subsequently, we believe that microarray analysis of esophageal tumors will allow us 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 will identify overlapping sets of patients at high risk for recurrence. In this proposal, we intend to explore the relationship between data obtained from microarray analysis of the primary tumors and analysis of occult lymph node involvement. We believe that the combination of this comprehensive molecular staging will allow us to significantly improve upon the current staging of esophageal adenocarcinoma. In addition, we believe that this research will answer some very interesting questions about tumor biology and metastasis in esophageal cancer. ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA090665-07
Application #
7215585
Study Section
Special Emphasis Panel (ZRG1-CBSS (01))
Program Officer
Thurin, Magdalena
Project Start
2001-03-09
Project End
2010-02-28
Budget Start
2007-03-07
Budget End
2008-02-29
Support Year
7
Fiscal Year
2007
Total Cost
$260,665
Indirect Cost
Name
University of Pittsburgh
Department
Surgery
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Chen, Zhang-Hui; Yu, Yan P; Tao, Junyan et al. (2017) MAN2A1-FER Fusion Gene Is Expressed by Human Liver and Other Tumor Types and Has Oncogenic Activity in Mice. Gastroenterology 153:1120-1132.e15
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Dulak, Austin M; Stojanov, Petar; Peng, Shouyong et al. (2013) Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet 45:478-86
Pennathur, Arjun; Gibson, Michael K; Jobe, Blair A et al. (2013) Oesophageal carcinoma. Lancet 381:400-12
Dulak, Austin M; Schumacher, Steven E; van Lieshout, Jasper et al. (2012) Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis. Cancer Res 72:4383-93
Choy, Bonnie; Bandla, Santhoshi; Xia, Yinglin et al. (2012) Clinicopathologic characteristics of high expression of Bmi-1 in esophageal adenocarcinoma and squamous cell carcinoma. BMC Gastroenterol 12:146
Ferris, Robert L; Stefanika, Patrick; Xi, Liqiang et al. (2012) Rapid molecular detection of metastatic head and neck squamous cell carcinoma as an intraoperative adjunct to sentinel lymph node biopsy. Laryngoscope 122:1020-30
Pennathur, Arjun; Awais, Omar; Luketich, James D (2010) Minimally invasive esophagectomy for Barrett's with high-grade dysplasia and early adenocarcinoma of the esophagus. J Gastrointest Surg 14:948-50
Pennathur, Arjun; Zhang, Jie; Chen, Haiquan et al. (2010) The ""best operation"" for esophageal cancer? Ann Thorac Surg 89:S2163-7
Pennathur, Arjun; Farkas, Andrew; Krasinskas, Alyssa M et al. (2009) Esophagectomy for T1 esophageal cancer: outcomes in 100 patients and implications for endoscopic therapy. Ann Thorac Surg 87:1048-54; discussion 1054-5

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