Secretory cell outgrowth, PAX2 and serous carcinogenesis in the Fallopian tube
The 'p53 signature' is a benign secretory cell outgrowth in the distal Fallopian tube that shares properties with ovarian serous cancer--including p53 mutations--and is a putative serous cancer precursor. We expanded the precursor definition to all secretory cell outgrowths (SCOUTs) of 30...
Saved in:
Published in | The Journal of pathology Vol. 222; no. 1; pp. 110 - 116 |
---|---|
Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Chichester, UK
John Wiley & Sons, Ltd
01.09.2010
Wiley |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | The 'p53 signature' is a benign secretory cell outgrowth in the distal Fallopian tube that shares properties with ovarian serous cancer--including p53 mutations--and is a putative serous cancer precursor. We expanded the precursor definition to all secretory cell outgrowths (SCOUTs) of 30 or more cells and scored normal (N) and altered (A) expression of both p53 and PAX2, a gene down-regulated in ovarian and endometrial cancer. SCOUTs were identified by BCL2/p73 staining in tubes from women with serous carcinoma, inherited mutations in BRCA1 or BRCA2 and controls. SCOUTs were prevalent in both proximal and distal tube and significantly associated with serous carcinoma versus the others (p < 0.001); 89% were PAX2 (A) and 26% were PAX2 (A)/p53 (A) (p53 signatures). PAX2 (A)/p53 (N) SCOUTs were free of p53 mutations; however, 12 of 13 p53 signatures were PAX2 (A). A tubal carcinoma and contiguous SCOUT were p53 (A)/PAX2 (A) and shared the same p53 mutation. SCOUTs are discretely localized alterations commonly containing altered expression of multiple genes within histologically benign tubal epithelium. Geographic distribution in the tube varies by genotype and immunophenotype, from regionally unrestricted (PAX2) to greater likelihood specific area (fimbria) of shared prevalence (PAX2 and p53). This study reveals, for the first time, an entity (SCOUT) that is associated with serous cancer, expands the topography of altered PAX2 expression in the female genital tract mucosa and highlights another potential pathway disturbance involved in early serous carcinogenesis in the Fallopian tube. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
---|---|
Bibliography: | http://dx.doi.org/10.1002/path.2739 Columbia Hospital for Women Research Foundation ark:/67375/WNG-8N0QMS0R-3 Francis Ward Paine ArticleID:PATH2739 NCI - No. 1R21CA124688-01A1 TSA Pemberton Funds istex:8619F0B29BD852B14D4A658F760C8857789396A1 No conflicts of interest were declared. These authors contributed equally as first and senior authors, respectively. These authors contributed equally as first and senior authors respectively. |
ISSN: | 0022-3417 1096-9896 |
DOI: | 10.1002/path.2739 |