Molecular pathogenesis of endometrial and ovarian cancer

Issue title: Translational Pathology of Early Cancer

Guest editors: Sudhir Srivastavax and William E. Grizzley

Article type: Research Article

Authors: Merritt, Melissa A. | Cramer, Daniel W.^{; *}

Affiliations: Brigham and Women's Hospital, Department of Obstetrics and Gynecology Epidemiology Center, Boston, MA, USA | [x] Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA | [y] Department of Pathology, Division of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence: [*] Corresponding author: Daniel W. Cramer, M.D., Sc.D., Brigham and Women's Hospital, Obstetrics and Gynecology Epidemiology Center, 221 Longwood Avenue RDB 365, Boston MA 02115, USA. Tel.: +1 617 732 4895; Fax: +1 617 732 4899; E-mail: [email protected].

Abstract: Pregnancy, breastfeeding, and oral contraceptive pill use interrupt menstrual cycles and reduce endometrial and ovarian cancer risk. This suggests the importance of turnover within Mullerian tissues, where the accumulation of mutations in p53 and PTEN has been correlated with number of cycles. The most common type of endometrial cancer (Type I) is endometrioid and molecular abnormalities include mutations in PTEN, KRAS and β-catenin. The Type I precursor is Endometrial Intraepithelial Neoplasia which displays PTEN defects. Type II endometrial cancer (whose precursors are less clear) includes serous and clear cell tumors and the most common alteration is p53 mutation. For ovarian cancer, histopathologic types parallel endometrial cancer and include serous, mucinous, endometrioid, and clear cell; some molecular features are also shared. The most frequent type of ovarian cancer is high grade serous that often displays p53 mutation and its precursor lesions may originate from normal-appearing fallopian tube epithelium that contains a p53 “signature”. Mutations in KRAS, BRAF and PTEN are described in mucinous, endometrioid and low grade serous cancers and these may originate from ovarian cortical inclusion cysts. A consideration of molecular and other pathogenetic features, like epidemiology and histopathology, may provide a better understanding of endometrial and ovarian cancer.

Keywords: Ovarian cancer, Endometrial cancer, p53, PTEN, KRAS, Precursor lesions, Endometrial intraepithelial neoplasia, Fallopian tube, Cortical inclusion cysts, mullerian, epidemiology, risk factors, Type I, Type II, serous, mucinous, endometrioid, clear cell

DOI: 10.3233/CBM-2011-0167

Journal: Cancer Biomarkers, vol. 9, no. 1-6, pp. 287-305, 2011