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Gynecol Oncol. 2008 May;109(2):168-73. doi: 10.1016/j.ygyno.2008.01.012. Epub 2008 Mar 14.

A candidate precursor to pelvic serous cancer (p53 signature) and its prevalence in ovaries and fallopian tubes from women with BRCA mutations.

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1
The Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.

Abstract

BACKGROUND:

Early serous carcinomas predominate in the fimbria of women with BRCA mutations (BRCA+). An entity in non-neoplastic mucosa sharing several properties of early serous carcinomas--the "p53 signature"--has been described in the distal fallopian tube and proposed as a precursor to serous carcinomas. This study compared the prevalence of p53 signatures in ovarian cortical inclusion cysts (CICs) and fallopian tubes from BRCA+ women and explored their relationship.

DESIGN:

All tissues from 75 completely excised ovaries and tubes obtained during prophylactic surgery were studied by conventional microscopy, immunostaining for p53, and in selected cases, gamma-H2AX (DNA damage). P53 signatures were defined as 12 or more consecutive p53-positive secretory cell nuclei. Their prevalence in fallopian tubes and CICs was recorded, compared to an existing database of consecutive women without a suspicion of BRCA+ or ovarian cancer, and correlated with the number of CICs.

RESULTS:

Tubal p53 signatures were detected in 29 of 75 cases (38%); 20 of 30 (66%) signatures examined were gamma-H2AX-positive. One ovary contained a small gamma-H2AX negative p53 signature on the ovarian surface; no p53 signatures were identified in CICs. The prevalence of BRCA+ p53 tubal signatures was similar to that of women with unknown BRCA status (38 v 33%). Presence of p53 signatures did not correlate with number of CICs.

CONCLUSIONS:

p53 signatures were common in the fallopian tubes of BRCA+ women, were not identified in CICs, and did not correlate with the latter. The tubal p53 signature merits serious consideration as an important early event in serous carcinogenesis in BRCA+ women.

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PMID:
18342932
PMCID:
PMC2746001
DOI:
10.1016/j.ygyno.2008.01.012
[Indexed for MEDLINE]
Free PMC Article
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