Distinguishing between different types of endometrial cancers is currently based on histology; however, categorizing endometrial cancer tissues is often difficult, and specialists frequently disagree on the classification of individual cases.
“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,” said Dr. Levine.
The investigators showed approximately 25% of tumors classified by pathologists as high-grade endometrioid had frequent TP53 mutations as well as extensive copy number alterations. In contrast, most endometrioid tumors have few copy number alterations or TP53 mutations, although frequent mutations in other well known cancer-associated genes, including PTEN and KRAS, occur. This suggests some high-grade endometrioid tumors have developed a pattern of alterations similar to that of serous tumors, and may benefit from a similar course of treatment.
Dr. Levine said that based on these results, “we have a number of molecularly targeted clinical trials open around the country that take advantage of the unique mutational landscape of endometrial cancer, as reported in this publication. We are actively analyzing tumor samples from these clinical trials to see if we can correlate molecular features with response to treatment.”
“Pathologists have some tools to reproduce these subtypes, such as immunohistochemistry markers for MSI, which would reproduce the MSI subtype,” Dr. Levine added. “But the novel POLE subtype could not be identified at present. The overlap between high grade endometrioid cases and serous cases remains a diagnostic dilemma for specialty pathologists.”
The current research “did not address risk of getting the disease, as it only studied established tumors to define the molecular landscape of the disease,” Dr. Levine said. “Other ongoing research is being performed to get at the issue of genetic risk and the need for testing.”
These results represent the latest findings from the TCGA, funded and managed by the National Institutes of Health’s (NIH) National Cancer Institute and National Human Genome Research Institute (NHGRI).
“With this latest study in a series of 20 planned TCGA tumor type characterizations, more genomic similarities are emerging between disparate tumor types,” NIH Director Francis S. Collins, MD, PhD, noted in a press release. “Teasing out heretofore unknown genomic markers or mutations in various cancers is again proving the value of TCGA.”3
The TCGA Research Network consists of more than 150 researchers at dozens of US institutions (http://cancergenome.nih.gov/abouttcga/overview), who have generated data and published analyses on glioblastoma multiforme, ovarian serous adenocarcinoma, colorectal adenocarcinoma, lung squamous cell carcinoma, and invasive breast cancer. Data generated by TCGA are freely available at the TCGA Data Portal and CGHub; data specific to this study are at: https://tcga-data.nci.nih.gov/docs/publications/ucec_2013/.
1. The Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497:67-73. Available at: http://www.nature.com/nature/journal/v497/n7447/full/nature12113.html. Accessed May 16, 2013.
2. Siegel R, Haishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11-30.
3. The Cancer Genome Atlas Research Network. Study establishes basis for genomic classification of endometrial cancers. Press release. Available at: http://cancergenome.nih.gov/newsevents/newsannouncements/TCGA_UCEC_press_release_2013. Accessed May 16, 2013.