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. STUDY DESIGN: Program participants with a diagnosis of ovarian cancer or pe ritoneal serous papillary carcinoma were identified and their demographic c haracteristics, ultrasonographic findings, CA 125 results, operative report s, and pathology slides reviewed. Immunohistochemical analysis of p53, bcl- 2, HER-2/neu, and nm23 HI expression was performed on tumor tissues from mu ltiple metastatic sites, and germline BRCA1 and BRCA2 mutations were identi fied. RESULTS: Three stage I ovarian cancers and 7 cases of peritoneal serous pap illary carcinoma were diagnosed from among 1261 program participants. Ultra sonographic abnormalities triggered surgical exploration in all 3 cases of stage I disease. Elevated levels of CA 125 were the harbinger in 2 of 7 cas es of peritoneal serous papillary carcinoma, abnormal ultrasonographic find ings prompted diagnosis in 2 of 7 cases, and 3 of 7 women had abdominal sym ptoms 5, 6, and 16 months after screening. Results of immunohistochemical s tudies suggested multifocal disease in 5 of 7 patients with peritoneal sero us papillary carcinoma. At least 3 of the patients with peritoneal serous p apillary carcinoma carry BRCA1 185delAG mutations. CONCLUSION: Multifocal peritoneal serous papillary carcinoma may be a pheno typic variant of familial ovarian cancer, and screening strategies for thes e women cannot rely on ultrasonography and CA 125 testing to detect early d isease.