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Endometrial cancers have been broadly classified into two groups: type 1, which are linked to obesity and estrogen excess and have a favorable prognosis, and type 2, which are mostly serous carcinomas and have an unfavorable prognosis. Based on these clinical subtypes, physicians make treatment decisions about chemotherapy and radiation therapy.
Now, investigators have conducted genomic and proteomic analyses of 373 endometrial tumors to further classify endometrial cancer into four groups: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. They discovered that ERBB2 (the gene encoding for HER2) was focally amplified in 25% of serous and serous-like tumors, suggesting that the use of anti-HER2 therapy may be beneficial in this patient subpopulation. They also found that a subtype of endometrial cancer shares features with high-grade ovarian cancers and basal-like breast cancer, suggesting potential similarities in treatment response. The investigators concluded that these genomic subtypes will help clinicians determine optimal therapies for patients and may help in the selection of targeted approaches.
The Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature 2013 May 2; 497:67.
Comment
It has long been recognized that cancers have distinct molecular characteristics that may not be well depicted in pathology reports but that can serve as both prognostic and predictive markers. In fact, breast cancer was the first solid tumor in which molecular subtypes were found to have a huge impact on prognosis and treatment (Nature 2000; 406:747). Now, genomic assays are routinely used in breast cancer to aid clinicians in making treatment decisions (e.g., JW Oncol Hematol Nov 15 2011). The current study is a huge step toward applying this technique in other malignancies. In the era of targeted therapies, identifying pathways that drive tumor growth will be essential for developing successful approaches.