Esophageal Cancer Research Defines Precise Features of Tumors

A new study from a national team of genomic experts shows striking differences in some types of esophageal tumors and argues against treatment approaches that sometimes view esophageal cancer and stomach tumors as a single or similar disease.

Reported in the journal Nature, the study suggests re-classifying tumors based on patterns and alterations of gene mutations. The study found, for example, that one common type of esophageal cancer, called squamous cell carcinoma, had three amplified genes (CCDN1, SOX2 and TP63), whereas the other common type of esophageal cancer, called adenocarcinoma, had an over-abundance of four different genes (ERBB2, VEGFA, GATA4 and GATA6). Also, the molecular signatures often changed based on the location of the tumor. Esophageal cancer can arise near the top of esophagus, the middle, or in the lower part near the junction of the stomach.

David Zhou, M.D., Ph.D., associate professor of Pathology and Laboratory Medicine at the University of Rochester Medical Center and the Wilmot Cancer Institute, was part of the Cancer Genome Atlas Research Network that studied this issue. A specialist in gastrointestinal cancers, he was among six pathology experts who reviewed tumors samples and confirmed the diagnosis of patients who volunteered to submit tissue to the research project.

The study is important, Zhou said, because if a tumor has certain genomic mutations the patient might be eligible for modern precision therapies that target those mutations. The research provides a framework for categorizing esophageal tumors and a foundation for new treatment approaches. It was funded by the National Institutes of Health and the Intramural Research Program.

The Genome Network, which consists of scientists from more than 100 institutions worldwide, analyzed the molecular features of 164 esophagus tumors (90 squamous carcinoma, 72 adenocarcinoma, and two esophageal cancers that were undifferentiated), 359 gastric tumors, and 36 additional tumors that arose near the stomach and the lower esophagus. 

Only 12 percent to 20 percent of people survive esophageal cancer for five years or longer.  The incidence of adenocarcinoma is rising dramatically, with some data suggesting that increases in the number of cases have been as high as 700 percent in recent decades, Zhou said. Adenocarcinoma is often associated with obesity and gastric reflux disease; the squamous cell type is usually associated with smoking, salted food, and excessive alcohol consumption.