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


METHODS
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.
Folkins
Ann K
AK
The Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Jarboe
Elke A
EA
Saleemuddin
Aasia
A
Lee
Yonghee
Y
Callahan
Michael J
MJ
Drapkin
Ronny
R
Garber
Judy E
JE
Muto
Michael G
MG
Tworoger
Shelley
S
Crum
Christopher P
CP
D000290:Adnexa Uteri / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000473:pathology*; D003560:Cysts / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage; D005187:Fallopian Tubes / Q000378:metabolism; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D016147:Genes, Tumor Suppressor; D006657:Histones / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010049:Ovarian Diseases / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000378:metabolism; D010386:Pelvic Neoplasms / Q000473:pathology*; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C468783:H2AX protein, human; D006657:Histones; D016159:Tumor Suppressor Protein p53