- Two clinical subtypes of esophageal carcinomas that differ profoundly at molecular level have been identified.
- According to this differentiation, esophageal adenocarcinomas are different from esophageal squamous cell carcinomas.
- The molecular characteristics of the tumors are more important than the place of their origin for clinical trials and new treatment decisions.
Two main types of esophageal cancer that differ markedly in their molecular characteristics have been identified.
Study states that these should be considered separate diseases.
‘The molecular differentiation will act as a definitive reference manual for researchers and drug developers seeking more effective clinical trials and new treatment approaches.’
A comprehensive analysis of 559 esophageal and gastric cancer samples, collected from patients around the world, reports two findings:
- the upper esophageal cancers more closely resemble cancers of the head and neck, while tumors formed in the lower part of the esophagus are similar to a subtype of stomach cancer
- Patients should be grouped according to these molecular subtype during clinical trials.
"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 esophageal cancer field and will serve as the definitive reference manual for researchers and drug developers seeking more effective clinical trials and new treatment approaches." Bass added.
Physicians have known for decades that esophageal cancers, when looked at under the microscope, fall into one of two categories:
- These begin in the flat cells lining the esophagus. Smoking and alcohol increases risk of adenocarcinomas and these resemble stomach or colorectal cancers.
Squamous cell carcinomas
- That begin in the cells that make mucus and other fluids. Gastroeophageal reflux disease and Barrett esophagus increases risk of these cancers, which are similar to some lung, skin, and head and neck cancers.
Esophageal cancer represents just 1% of new cancer diagnoses in the U.S.
Based on the analysis of data from 2009 to 2013, the number of new cases of esophageal cancer was 4.3 per 100,000 men and women per year. The number of deaths was 4.1 per 100,000 men and women per year.
Approximately 0.5% of men and women will be diagnosed with esophageal cancer at some point during their lifetime, based on 2011-2013 data.
In 2013, there were an estimated 36,857 people living with esophageal cancer in the United States.
The percentage of esophageal cancer related deaths is highest among people aged 65-74 years
It kills 4-in-5 patients within five years of diagnosis, and current treatment approaches often fail to help.
The cases of esophageal adenocarcinoma have increased over the last four decades, increasing seven-fold since the mid-1970s.
But the extent to which adenocarcinomas and squamous esophageal cancers differ molecularly and the relationship between esophageal adenocarcinoma and stomach adenocarcinoma was unknown.
"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." Peter added.
This study revealed that esophageal adenocarcinomas have striking molecular similarity to a class of stomach cancers called chromosomally unstable tumors
, which are differentiated by their structural chromosomal aberrations.
This detailed analysis of the disease will change the approach of oncologists 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 esophageal adenocarcinoma, a combination of pathways and therapeutic strategies will be successful.
The study is published in Nature
from The Cancer Genome Atlas (TCGA) Research Network.
- SEER Stat Fact Sheets: Esophageal Cancer - (https://seer.cancer.gov/statfacts/html/esoph.html)
- Adam Bass et al. Integrated genomic characterization of oesophageal carcinoma. Nature; (2017)