Study sheds light on esophageal cancer, offers insight into increasingly common disease

January 4, 2017, Van Andel Research Institute

A comprehensive analysis of 559 esophageal and gastric cancer samples, collected from patients around the world, suggests the two main types of esophageal cancer differ markedly in their molecular characteristics and should be considered separate diseases.

The study, published today in Nature from The Cancer Genome Atlas (TCGA) Research Network, includes two key takeaways. First, upper esophageal cancers more closely resemble cancers of the head and neck, while tumors further down in the esophagus are virtually indistinguishable from a subtype of . Second, cancer clinical trials should group patients according to molecular subtype—in general, grouping lower esophageal tumors with stomach cancers, while evaluating upper esophageal cancers separately.

"These findings add several layers of depth and sophistication to our current understanding of esophageal cancer genomics," said Adam Bass, M.D., co-leader of TCGA's esophageal cancer study and physician-scientist at Dana-Farber Cancer Institute. "Our hope is this work settles several long-standing uncertainties in the field and will serve as the definitive reference manual for researchers and drug developers seeking more effective clinical trials and new treatment approaches."

Physicians have known for decades that esophageal cancers, when looked at under the microscope, fall into one of two categories—adenocarcinomas, which resemble stomach or colorectal cancers, and squamous cell carcinomas, which are similar to some lung, skin, and head and neck cancers. What remained unknown was the extent to which adenocarcinomas and squamous esophageal cancers differ molecularly and the relationship between esophageal adenocarcinoma and stomach adenocarcinoma.

"We have shown that these clinical subtypes differ profoundly at the molecular level," said Peter W. Laird, Ph.D., a principal investigator in the international TCGA Research Network and a professor at Van Andel Research Institute. "These findings suggest that whether the tumor originates in the esophagus or the stomach is less relevant than the molecular characteristics of the individual tumors."

Esophageal cancer represents just 1 percent of new cancer diagnoses in the U.S. However, it kills 4-in-5 patients within five years of diagnosis, and current treatment approaches often fail to help. Additionally, cases of esophageal adenocarcinoma have skyrocketed over the last four decades, increasing seven-fold since the mid-1970s. Within the field, there has been great uncertainty regarding the relationship between this growing burden of esophageal adenocarcinoma and adenocarcinomas that occur in the stomach.

Results from this new report argue against the need to continue to debate the demarcations of esophageal and gastric adenocarcinoma and instead view gastroesophageal adenocarcinoma as a more singular entity, analogous to colorectal cancer. Specifically, this study revealed that esophageal adenocarcinomas have striking molecular similarity to a class of stomach cancers called chromosomally unstable tumors, the hallmark of which are significant structural chromosomal aberrations.

Oncologists say this nuanced view of the disease, including the detailed molecular taxonomy of esophageal adenocarcinomas, will likely change their approach to studies and treatment.

"It is clear from the TCGA data that esophageal squamous and esophageal adenocarcinomas are completely different diseases and should never be included in the same therapeutic trial," said Yelena Y. Janjigian, M.D., a gastrointestinal oncologist from Memorial Sloan Kettering Cancer Center who was not involved in the study. "In , it is likely a combination of pathways and therapeutic strategies that will be successful. The therapeutic significance of these alterations will be explored in follow-up studies."

Members of the TCGA Research Network team say these studies represent the work of dedicated collaborators, who seek to maximize results in search of new ways to battle .

"Studies from TCGA transcend the work of any one institution or individual," said Ilya Shmulevich, Ph.D., a principal investigator in the international TCGA Research Network and a professor at the Institute for Systems Biology. "These are massive undertakings that are possible only through contributions from hundreds of specialists and scientists around the world—people dedicate years of their lives to these projects in the hope of finding new treatments for people who are very sick."

Explore further: Oral bacterium related esophageal cancer prognosis in Japanese patients

More information: Integrated genomic characterization of oesophageal carcinoma, Nature, nature.com/articles/doi:10.1038/nature20805

Related Stories

Oral bacterium related esophageal cancer prognosis in Japanese patients

December 9, 2016
A type of bacterium usually found in the human mouth, Fusobacterium nucleatum (F. nucleatum), has been found to be related to the prognosis of esophageal cancer in Japanese patients by researchers from Kumamoto University, ...

Alcohol, obesity could raise esophageal cancer risk

July 28, 2016
(HealthDay)—Drinking plus being overweight may be a bad combo when it comes to risks for the two most common types of esophageal cancer, a new report warns.

Researchers discover gene variant associated with esophageal cancer

July 28, 2016
Researchers at University Hospitals Case Medical Center have discovered that a rare genetic mutation is associated with susceptibility to familial Barrett esophagus (FBE) and esophageal cancer, according to a new study published ...

AIDS patients face risk for esophageal, stomach cancers

September 24, 2012
People with AIDS are at increased risk for developing esophageal and stomach carcinoma as well as non-Hodgkin lymphomas (NHLs), according to a new study in Gastroenterology, the official journal of the American Gastroenterological ...

Biomarkers may help predict progression of Barrett's esophagus to esophageal adenocarcinoma

March 6, 2013
A series of microRNA expression signatures that may help to define progression of the precancerous condition Barrett's esophagus into esophageal adenocarcinoma was reported recently in Cancer Prevention Research, a journal ...

Recommended for you

Repurposing FDA-approved drugs can help fight back breast cancer

November 16, 2018
Screening Food and Drug Administration (FDA)-approved compounds for their ability to stop cancer growth in the lab led to the finding that the drug flunarizine can slow down the growth of triple-negative breast cancer in ...

New 'SLICE' tool can massively expand immune system's cancer-fighting repertoire

November 15, 2018
Immunotherapy can cure some cancers that until fairly recently were considered fatal. In addition to developing drugs that boost the immune system's cancer-fighting abilities, scientists are becoming expert at manipulating ...

Standard chemotherapy treatment for HPV-positive throat cancer remains the most effective, study finds

November 15, 2018
A new study funded by Cancer Research UK and led by the University of Birmingham has found that the standard chemotherapy used to treat a specific type of throat cancer remains the most effective.

Anti-malaria drugs have shown promise in treating cancer, and now researchers know why

November 15, 2018
Anti-malaria drugs known as chloroquines have been repurposed to treat cancer for decades, but until now no one knew exactly what the chloroquines were targeting when they attack a tumor. Now, researchers from the Abramson ...

Researchers identify a mechanism that fuels cancer cells' growth

November 14, 2018
Scientists at the UCLA Jonsson Comprehensive Cancer Center have identified sodium glucose transporter 2, or SGLT2, as a mechanism that lung cancer cells can utilize to obtain glucose, which is key to their survival and promotes ...

A new approach to detecting cancer earlier from blood tests: study

November 14, 2018
Cancer scientists led by principal investigator Dr. Daniel De Carvalho at Princess Margaret Cancer Centre have combined "liquid biopsy", epigenetic alterations and machine learning to develop a blood test to detect and classify ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.