TCGA Study of Esophageal Cancers Finds Features That Aid in Their Classification

Key Points

  • Researchers observed that the esophageal squamous cell cancers share more common features with head and neck squamous cell carcinomas than with esophageal adenocarcinomas.
  • There was also a striking resemblance between the esophageal adenocarcinomas and a subtype of stomach cancer characterized by chromosomal instability, called the CIN subtype.
  • The study found genomic alterations that may represent effective targets for therapy, including alterations of cell cycle genes and the alteration of ERBB2 in one third of the esophageal adenocarcinomas studied.

A new integrated genomic study by The Cancer Genome Atlas (TCGA) Research Network identified genetic alterations that distinguish the two most common subtypes of esophageal cancer.

Esophageal cancer is a rare cancer in the United States, but the 8th most frequently diagnosed cancer worldwide. It is usually diagnosed as either esophageal adenocarcinoma or esophageal squamous cell carcinoma by its appearance under the microscope. The findings of the TCGA study, published in Nature, suggest that esophageal squamous cell and adenocarcinoma are two separate diseases that should not be combined in clinical trials and may benefit from a molecular system of classification.

Findings

Scientists often find cancers of the esophagus difficult to define because they may look and behave like head and neck cancers or like stomach cancers. To better understand the distinction between esophageal cancer and anatomically related cancers, the authors compared the genomic alterations of 164 esophageal cancers to 359 stomach cancers and 275 head and neck cancers. They observed that the esophageal squamous cell cancers share more common features with head and neck squamous cell carcinomas than with esophageal adenocarcinomas. Interestingly, esophageal squamous cell carcinomas were particularly similar to head and neck squamous cell carcinomas that do not stem from human papillomavirus (HPV) infection, consistent with the finding that the cases of these esophageal cancers that were studied were negative for HPV infection.

By comparing esophageal adenocarcinoma to stomach cancers, the researchers noticed a striking resemblance between the esophageal adenocarcinomas and a subtype of stomach cancer characterized by chromosomal instability, called the CIN subtype. CIN stomach cancers, molecularly characterized in a 2014 TCGA study also published in Nature, were found in the area of the stomach closest to the esophagus. Though the authors observed that esophageal adenocarcinomas displayed slightly less chromosomal instability than CIN stomach cancers, they determined that these two cancer types form a distinct group when compared to similar cancers and that genomic analyses could not definitively separate them into groups.

In addition, the study found genomic alterations that may represent effective targets for therapy, including alterations of cell cycle genes and the alteration of ERBB2 in one third of the esophageal adenocarcinomas studied, which may be treated with inhibitors of its protein product, HER2.

Together, these results indicate that grouping esophageal cancers based on their molecular underpinnings may lead to improved methods for preventing, diagnosing, and treating these cancers.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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