Lessons from BRCA: The Tubal Fimbria Emerges as an Origin for Pelvic Serous Cancer
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Open Access
- 1 March 2007
- journal article
- review article
- Published by Marshfield Clinic Research Institute in Clinical Medicine & Research
- Vol. 5 (1), 35-44
- https://doi.org/10.3121/cmr.2007.702
Abstract
Ovarian epithelial cancer is diagnosed in approximately 25,000 women yearly in the United States, accounting for approximately 12,500 deaths. Of these tumors, serous cancer is the most lethal, due to its capacity to spread beyond the reproductive tract and involve the peritoneal surfaces or distant organs. Conventional classification systems designate tumor origins principally on the location of the largest tumor. However, despite the fact that the largest tumors typically involve the ovaries, demonstrations of a precise starting point for these tumors, including precursor lesions, have been inconsistent. In recent years, a major effort to prevent serous cancer in genetically susceptible women with mutations in BRCA1 or BRCA2 has spawned the practice of prophylactic salpingo-oophorectomy. This practice has surprisingly revealed that many early cancers in these women arise in the fallopian tube, and further studies have pinpointed the distal (fimbrial) portion as the most common site of origin. Emerging studies that carefully examine the fallopian tubes suggest a high frequency of early cancer in the fimbria in unselected women with ovarian and peritoneal serous carcinoma, raising the distinct possibility that a significant proportion of these tumors have a fimbrial origin. The evidence for these discoveries and their relevance to serous cancer classification, early detection and prevention are addressed in this review. A model for pelvic serous cancer is proposed that takes into account five distinct variables which ultimately impact on origin and tumor distribution: (1) location of target epithelium, (2) genotoxic stress, (3) type of epithelium, (4) mitigating genetic factors, and (5) tumor spread pattern. Ultimately, this model illustrates the importance of identifying cancer precursors, inasmuch as these entities are useful as both surrogate endpoints for their respective malignancies in epidemiologic studies and natural targets for cancer prevention.Keywords
This publication has 56 references indexed in Scilit:
- Intraepithelial Carcinoma of the Fimbria and Pelvic Serous Carcinoma: Evidence for a Causal RelationshipThe American Journal of Surgical Pathology, 2007
- Screening for gynaecological cancersEuropean Journal of Surgical Oncology, 2006
- Ovarian Cancer Screening: A Look at the EvidenceClinical Journal of Oncology Nursing, 2006
- Ovarian cancer and genetic susceptibility in relation to the BRCA1 and BRCA2 genes. Occurrence, clinical importance and interventionActa Obstetricia et Gynecologica Scandinavica, 2006
- Advances in the Recognition of Tubal Intraepithelial CarcinomaAdvances in Anatomic Pathology, 2006
- Hereditary breast and ovarian cancer: review and future perspectivesJournal of Molecular Medicine, 2005
- Origins and molecular pathology of ovarian cancerLaboratory Investigation, 2005
- Patterns of p53 Mutations Separate Ovarian Serous Borderline Tumors and Low- and High-grade Carcinomas and Provide Support for a New Model of Ovarian CarcinogenesisThe American Journal of Surgical Pathology, 2005
- Risk-Reducing Salpingo-Oophorectomy in BRCA Mutation Carriers: Role of Serial Sectioning in the Detection of Occult MalignancyJournal of Clinical Oncology, 2005
- Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancerNature Medicine, 2004