Serous Carcinogenesis in the Fallopian Tube
- 1 January 2008
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in International Journal of Gynecological Pathology
- Vol. 27 (1), 1-9
- https://doi.org/10.1097/pgp.0b013e31814b191f
Abstract
The fimbria is the most common site of early serous cancer (tubal intraepithelial carcinoma or STIC) in women with BRCA mutations (BRCA+). A candidate serous cancer precursor--the p53 signature--has been found in nonneoplastic secretory cells of the fimbria, suggesting serous carcinogenesis in the tube (SCAT). This study surveyed fallopian tubes from 3 populations to characterize the morphological and immunohistochemical correlates of SCAT. The SCAT sequence was defined by strong nuclear p53 staining and DNA damage (gamma-H2AX+) in secretory cells and subdivided morphologically by (1) degree of nuclear stratification, (2) proliferative index, and (3) degree of disorganized growth. Fallopian tubes from women without a current ovarian cancer, women with BRCA mutations, and women with a coexisting pelvic serous cancer were completely examined. p53 signatures exhibited cuboidal to pseudostratified, polarized p53+ epithelial segments with variable nuclear enlargement and a MiB1 index of 0% to 30%. Tubal intraepithelial carcinomas contained from single (uncommon) to multilayered, poorly polarized, uninterrupted neoplastic cell populations that completely displaced the normal mucosa; MiB1 index exceeded 45% and was usually more than 70%. An uncommon third category, p53-positive foci with features intermediate between p53 signatures and STICs, exhibited preserved epithelial polarity, pseudostratification, incomplete replacement of the adjacent normal ciliated cells, and a MiB1 index between 40% and 75%. Transitions from 1 category to another were documented. Combined with recent reports associating STICs with pelvic serous cancer, this continuum of epithelial change validates the SCAT sequence and the fimbrial secretory cell as the site of origin for many serous carcinomas.Keywords
This publication has 16 references indexed in Scilit:
- Intraepithelial Carcinoma of the Fimbria and Pelvic Serous Carcinoma: Evidence for a Causal RelationshipThe American Journal of Surgical Pathology, 2007
- Cancer Statistics, 2007CA: A Cancer Journal for Clinicians, 2007
- The Tubal Fimbria Is a Preferred Site for Early Adenocarcinoma in Women With Familial Ovarian Cancer SyndromeThe American Journal of Surgical Pathology, 2006
- Clinical and pathologic findings of prophylactic salpingo-oophorectomies in 159 BRCA1 and BRCA2 carriersGynecologic Oncology, 2006
- BRCA-Mutation–Associated Fallopian Tube CarcinomaObstetrics & Gynecology, 2005
- Intraperitoneal serous adenocarcinoma: A critical appraisal of three hypotheses on its causeAmerican Journal of Obstetrics and Gynecology, 2004
- Pathologic Findings in Prophylactic Oophorectomy Specimens in High-Risk WomenGynecologic Oncology, 2002
- Absence of premalignant histologic, molecular, or cell biologic alterations in prophylactic oophorectomy specimens fromBRCA1 heterozygotesCancer, 2000
- Ovarian dysplasia in prophylactic oophorectomy specimensCancer, 1999
- Early de novo ovarian carcinoma. A study of fourteen casesCancer, 1994