Peritoneal Serous Papillary Carcinoma, a Phenotypic Variant of Familial Ovarian Cancer: Implications for Ovarian Cancer Screening
abstract & commentary
Source: Karlan BY, et al. Am J Obstet Gynecol 1999; 180:917-928.
Synopsis: 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 and associates have reported their experience with a high-risk ovarian cancer screening program. In addition to demographic characteristics, sonography findings, CA 125 results, operative reports, and pathology slides were reviewed. They also performed immunohistochemical analysis of p53, bcl-2, HER-2/neu, and nm23 H1 expression on tumor tissues from multiple metastatic sites. In addition, BRCA1 and BRCA2 mutations were identified. During the study period, Karlan et al diagnosed three stage I ovarian cancers and seven cases of peritoneal serous papillary carcinoma among 1261 program participants. Ultrasonographic findings prompted surgery in all three cases of stage I disease. Elevated levels of CA 125 were the harbinger in two of seven cases of primary peritoneal cancer; abnormal sonographic findings prompted diagnosis in two of seven cases; and three of seven women had abdominal symptoms five, six, and 16 months after screening. Results of immunohistochemical studies suggested multifocal disease in five of seven patients with primary peritoneal cancer. At least three of the patients with primary peritoneal cancer carried BRCA1 185delAG mutations. Karlan et al conclude that multifocal primary peritoneal cancer 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.
Comment by David M. Gershenson, MD
This report represents an extraordinary confluence of several exciting, emerging areas of research in ovarian cancer and related conditions. Currently, there is no effective screening method for this devastating disease. Although several groups have studied serum CA 125 and sonography in the general population, their lack of sensitivity and specificity have been major barriers to success. Therefore, several groups have focused their attention on so-called high-risk women. Since Swerdlow first described peritoneal cancer in 1959, there has been considerable confusion surrounding this malignancy, particularly in terms of its histologic characterization, its nomenclature, and its biologic behavior. Most studies have indicated that peritoneal cancer looks and behaves like advanced ovarian cancer, and we treat it in an identical manner. Harvard investigators have reported on the molecular pathogenesis of peritoneal cancer. They suggest that, in contradistinction to primary ovarian cancer, which appears to have a uniclonal origin, at least some peritoneal cancers have a multifocal origin. The main message of this report is that, despite relatively close surveillance, peritoneal cancer developed in seven women. At least some of these women had a mutation of the BRCA1 gene. The importance of this information cannot be overemphasized in terms of the implications for women who are enrolled in high-risk screening programs worldwide. However, further information will be necessary to draw definitive conclusions regarding the incidence of peritoneal cancer both with and without prophylactic oophorectomy. Although not directly addressed by this report, information about peritoneal cancer after prophylactic oophorectomy is of paramount importance in this patient population. The incidence was 11% in one study and 1.8% in a much larger cohort. It will likely be several years before we learn the true incidence of peritoneal cancer after prophylactic oophorectomy in these high-risk women.
Primary peritoneal cancer differs from primary epithelial ovarian cancer with regard to:
a. biologic behavior.
b. histopathology.
c. presence of BRCA1 mutation in some cases.
d. pathogenesis (unifocal vs multifocal).
e. treatment.
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