Genetic alterations of the WT1 gene in papillary serous carcinoma of the peritoneum.
OBJECTIVE
The Wilms' tumor (WT1) gene product is consistently detectable in both normal ovarian germinal epithelium and human mesothelium. Ovarian carcinomas frequently exhibit alterations in WT1 function. Papillary serous carcinoma of the peritoneum (PSCP) is believed to develop de novo from the peritoneal lining (mesothelium) of the pelvis and abdomen. The purpose of this study was to determine if genetic alterations of the WT1 gene are associated with the development of PSCP.


METHODS
Normal and tumor tissue specimens were retrieved from patients with stage III and IV PSCP (n = 38) and serous epithelial ovarian carcinoma (n = 38). Immunohistochemistry was performed using the anti-WT1 (C-19) antibody. Loss of heterozygosity (LOH) was performed at the WT1 locus. Clinical data were obtained and correlated with molecular findings.


RESULTS
Loss of normal WT1 expression was detected in 18 (51%) of 35 PSCP specimens and 18 (53%) of 34 ovarian carcinoma specimens. Six (27%) of 22 PSCP specimens and 3 (13%) of 24 ovarian carcinoma specimens had LOH at the WT1 locus (P = 0.27). Normal WT1 gene expression was maintained in 86% of tumors exhibiting LOH. Genetic alterations of the WT1 gene were not predictive of survival, nor were they associated with other clinical or molecular factors.


CONCLUSIONS
Genetic alterations of the WT1 gene are associated with the development of PSCP. The loss of normal WT1 gene expression is a common event in both PSCP and advanced ovarian carcinoma, likely resulting from down-regulation by other regulatory factors-not from inactivating gene mutation and subsequent allelic loss.
Schorge
J O
JO
Laboratory of Gynecologic Oncology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Miller
Y B
YB
Qi
L J
LJ
Muto
M G
MG
Welch
W R
WR
Berkowitz
R S
RS
Mok
S C
SC
D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018283:Cystadenocarcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D025721:WT1 Proteins
D004268:DNA-Binding Proteins; D014157:Transcription Factors; D025721:WT1 Proteins