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Molecular alterations in the pathogenesis of endometrial adenocarcinoma. Therapeutic implications

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Summary

Molecular genetic evidence indicates that endometrial carcinoma likely develops as the result of a multistep process of oncogene activation and tumor suppressor gene inactivation. These molecular alterations appear to be specific for Type I (endometrioid) and Type II (non endometrioid) cancers. Type I cancers are characterized by mutation of PTEN, KRAS2, defects in DNA mismatch repair, as evidenced by the microsatellite instability phenotype, and a near diploid karyotype. Type II cancers often contain mutations of TP53 and Her-2/neu and are usually nondiploid. The clinical value of many of these molecular markers is now being tested and it may help to refine diagnosis and establish an accurate prognosis. Furthermore, some of these tumor biomarkers constitute the targets for emerging therapies. Transtuzumab against Her-2/neu and bevacizumab against VEGF overexpressing carcinomas are among the promising novel treatments. Additional translational research is needed to identify molecular and genetic alterations with potential for therapeutic interventions.

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Authors and Affiliations

  1. Radiation Oncology Service. La Princesa University Hospital, Autonoma University, C/Diego de León, 62, 28006, Madrid, Spain

    Laura Cerezo MD

  2. Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis. EE.UU.

    Higinia Cárdenes

  3. Department of Pathology, Indiana University School of Medicine, Indianapolis. EE.UU.

    Helen Michael

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  1. Laura Cerezo MD
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  2. Higinia Cárdenes
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Correspondence to Laura Cerezo MD.

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Supported by an unrestricted educational grant by Bristol-Myers Squibb.

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Cerezo, L., Cárdenes, H. & Michael, H. Molecular alterations in the pathogenesis of endometrial adenocarcinoma. Therapeutic implications. Clin Transl Oncol 8, 231–241 (2006). https://doi.org/10.1007/BF02664933

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