Peritoneal serous papillary carcinoma, a phenotypic variant of familial ovarian cancer: implications for ovarian cancer screening.
OBJECTIVE
Our purpose was to report the cancers arising during a familial ovarian cancer screening program and investigate the tumor's clonality and association with BRCA1 and BRCA2 mutations.


METHODS
Program participants with a diagnosis of ovarian cancer or peritoneal serous papillary carcinoma were identified and their demographic characteristics, ultrasonographic findings, CA 125 results, operative reports, and pathology slides reviewed. Immunohistochemical analysis of p53, bcl-2, HER-2/neu, and nm23 H1 expression was performed on tumor tissues from multiple metastatic sites, and germline BRCA1 and BRCA2 mutations were identified.


RESULTS
Three stage I ovarian cancers and 7 cases of peritoneal serous papillary carcinoma were diagnosed from among 1261 program participants. Ultrasonographic abnormalities triggered surgical exploration in all 3 cases of stage I disease. Elevated levels of CA 125 were the harbinger in 2 of 7 cases of peritoneal serous papillary carcinoma, abnormal ultrasonographic findings prompted diagnosis in 2 of 7 cases, and 3 of 7 women had abdominal symptoms 5, 6, and 16 months after screening. Results of immunohistochemical studies suggested multifocal disease in 5 of 7 patients with peritoneal serous papillary carcinoma. At least 3 of the patients with peritoneal serous papillary carcinoma carry BRCA1 185delAG mutations.


CONCLUSIONS
Multifocal peritoneal serous papillary carcinoma may be a phenotypic variant of familial ovarian cancer, and screening strategies for these women cannot rely on ultrasonography and CA 125 testing to detect early disease.
Karlan
B Y
BY
Departments of Obstetrics and Gynecology, Pediatrics and Medical Genetics, and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Baldwin
R L
RL
Lopez-Luevanos
E
E
Raffel
L J
LJ
Barbuto
D
D
Narod
S
S
Platt
L D
LD
D000328:Adult; D000368:Aged; D024682:BRCA2 Protein; D018394:CA-125 Antigen / Q000032:analysis; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D030342:Genetic Diseases, Inborn / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008403:Mass Screening / Q000379:methods / Q000592:standards; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D010534:Peritoneal Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics; D018615:Ultrasonography, Doppler, Color
D024682:BRCA2 Protein; D018394:CA-125 Antigen; D009363:Neoplasm Proteins; D014157:Transcription Factors