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Main esophageal cancers show distinct molecular differences
The two major types of esophageal cancer, esophageal adenocarcinoma and esophageal squamous cell carcinoma, show distinct molecular characteristics and should therefore be approached as separate entities in clinical trials, according to new research published in Nature.
While it is known that EACs histologically resemble gastric and colorectal cancers and ESCCs histologically resemble squamous cell carcinomas in other organs, this study reveals the extent to which these cancers differ on a molecular level, according to a press release. Specifically, ESCC showed a stronger molecular resemblance to SCCs in other organs than to EAC, whereas EAC showed a strong molecular resemblance to chromosomally unstable gastric adenocarcinoma.
“We have shown that these clinical subtypes differ profoundly at the molecular level,” Peter W. Laird, PhD, an investigator at The Cancer Genome Atlas Research Network and a professor at Van Andel Research Institute, said in a press release. “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.”
Laird and colleagues performed comprehensive molecular analyses of 164 esophageal tumors, 359 gastric adenocarcinomas and 36 gastro-esophageal junction adenocarcinomas from patients in both Eastern and Western nations.
The results suggested EACs and ESCCs have lineage-specific alterations that drive their progression; that ESCCs can be characterized by three molecular subtypes; that EACs and ESCCs show differences in frequent genomic amplifications; and that EACs strongly resemble chromosomally unstable gastric adenocarcinoma, distinct from other gastric tumor subtypes (although certain molecular features like DNA hypermethylation occurred more frequently in EAC). The results also did not support an etiologic role for human papilloma virus in ESCCs.
“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,” Yelena Y. Janjigian, MD, a gastrointestinal oncologist from Memorial Sloan Kettering Cancer Center who was not involved in the study, said in the press release. “In esophageal adenocarcinoma, 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.”
“These findings add several layers of depth and sophistication to our current understanding of esophageal cancer genomics,” Adam Bass, MD, an investigator in The Cancer Genome Atlas esophageal cancer study and physician-scientist at Dana-Farber Cancer Institute, said in the press release. “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.” – by Adam Leitenberger
Disclosures: The researchers report no relevant financial disclosures.