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Genomic Analysis of Endometrial Tumors

Genomic classification of endometrial tumors could help guide treatment strategies, according to a new analysis. The study also revealed 4 novel endometrial tumor subtypes and found similarities to other cancers.

Cancer of the endometrium, the tissue that lines the uterus, is the fourth most common cancer among women in the United States. Experts predict that close to 50,000 women will be diagnosed with the disease in 2013, with more than 8,000 deaths.

Clinically, endometrial cancers fall into 2 categories: endometrioid (type I) and serous (type II) tumors. Type I is linked to excess estrogen, obesity and a favorable prognosis. Type II is more common in older women and generally has a less favorable outcome. Pathologists currently classify endometrial tumors by examining tissue under a microscope. Categorizing these tissues can be difficult, and specialists often disagree on the diagnosis.

Investigators in The Cancer Genome Atlas (TCGA) Research Network undertook a comprehensive genomic analysis of nearly 400 endometrial tumors. TCGA is funded and managed by NIH’s National Cancer Institute (NCI) and National Human Genome Research Institute (NHGRI). The study appeared on May 2, 2013, in Nature.

The researchers found that about 25% of tumors classified by pathologists as high-grade endometrioid have a pattern of genetic alterations much like that of serous tumors. This suggests these tumors may benefit from a similar course of treatment.

The researchers found many genomic characteristics that endometrial cancers share with other tumor types. Previous TCGA research showed that a form of ovarian cancer (high-grade serous ovarian carcinoma) and a subtype of breast cancer (basal-like breast cancer) share many genomic features. The new study revealed that endometrial serous carcinoma also has some of these characteristics. Surprisingly, the researchers found similarities between endometrioid and colorectal tumors as well. These parallels might now be exploited for future therapies.

Four novel genomic-based subtypes of endometrial cancer also emerged from the analysis. This knowledge could help inform new diagnostic and treatment approaches.

“This study highlights the fact that some tumors with the same characterization by pathologists may have very different molecular features. That’s where these findings will be directly implemented in additional research, and also in the context of clinical trials,” says study co-leader Dr. Douglas A. Levine of Memorial Sloan-Kettering Cancer Center.

“Each tumor subtype might warrant dedicated clinical trials because of the marked genomic differences between them that are indicative of different drivers of cancer,” says study co-leader Dr. Elaine Mardis, at Washington University School of Medicine in St. Louis. “Developing therapies for each subtype independent of the other may improve outcomes, as has been shown in breast cancer.”