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Ovarian cancer will be diagnosed in an estimated 26 700 women in the United States in 19% and approximately 14 800 women will die of the disease (7). Of the 26 700 new cases, roughly 6000 will be diagnosed while cancer is confined to the ovaries and 4000 will be confined to the pelvis. Thus, more than 16 000 women will have advanced stage disease (International Federation of Gynecology and Obstetrics in and IV) at the time of diagnosis. The 5-year survival rate for patients with ovarian cancer confined to the ovaries is reported to be 91 % by the Surveillance, Epidemiology, and End Results' Program of the National Cancer Institute (7). In contrast, the survival rate is only 23% for patients with stage III or IV disease. Overall 5-year survival rates for patients with ovarian cancer has improved from 32% in the early 1960s to 42% in the late 1980s (2). Most of this improvement can be attributed to improvements in surgery and chemotherapy. There has been little change in the rate of early diagnosis. While it is quite likely that continued improvements in chemotherapy and more accessibility to proper surgical treatment will be able to improve survival slightly over the next few decades, significant improvement in survival rates for women with epithelial ovarian cancer will depend on improved understanding of the biology of these cancers so that methods of early detection and prevention can be developed. The analysis of the microscopic characteristics of the ovaries of women from familial and hereditary breast and ovarian cancer families reported in this issue of the Journal by Salazar et ai. (J) is a valuable contribution to our knowledge about the biology of ovarian tissue in women at increased risk of developing ovarian cancer. These authors have studied the histologic features of ovarian tissue removed from women undergoing prophylactic oophorectomy because of familial or hereditary ovarian cancer and have compared these histologic features to ovarian tissue from 20 women undergoing oophorectomy for a variety of benign gynecologic disorders. Although evaluation of the study cases reveals that only nine of the 20 patients are known to be BRCA positive, the family histories indicate that most of the patients are at significant risk of belonging to a hereditary breast-ovary cancer family, and a large percentage of the remaining 10 patients are probably BRCA1 positive on the basis of their family history. In a similar fashion, the control population is not a pure low-risk population, since neither extensive family histories nor BRCA1 testing was available for the control subjects. Despite the above deficiencies, the populations chosen are reasonably likely to represent cancer-prone versus non-cancerprone individuals. The authors found two occult epithelial ovarian cancers that are 500 times the expected incidence for women in that age group, since, based on epidemiologic data, the incidence of ovarian cancer in women aged 35-44 years is 10 per 100 000 (4). In addition, they found a statistically significant increase in incidence of papillomatosis, inclusion cysts, epithelial invagination, epithelial pseudostratification, and increased stromal activity. All of these characteristics have been postulated by various investigators to be potentially premalignant histologic features (5). The investigators could not, however, identify a transition from any of the above features to either low malignant potential or invasive epithelial cancer of the ovary. The identification of a premalignant ovarian abnormality has eluded investigators. Bourne and Lynch (6) described a comparison between an ultrasound screening study of a random population versus an ultrasound screening study of women with an ovarian cancer family history and showed an increased incidence of primary ovarian cancer, benign epithelial tumors, bilateral masses, and mixed ovarian lesions in women with a family history of ovarian cancer. Puls et al. (7) studied ovarian cystadenocarcinomas and found what they described as transition from benign cystadenomas to malignant lesions. They postulated that benign cystadenomas might be precursors of epithelial ovarian cancer in some cases. Other authorities have questioned this theory. To date, there are no proven premalignant lesions for epithelial ovarian cancer. Nor is it known whether or not tumors of low malignant potential represent an intermediate step between a benign lesion and an invasive cancer. Although the study by Salazar et al. (3) in this issue of the Journal does not establish that the epithelial abnormalities described are premalignant changes that will develop into invasive ovarian cancer, they do add further indirect evidence that such precancerous abnormalities do exist. Identification of such abnormalities could greatly increase our knowledge about the pathogenesis of this disease. Understanding the pathogenesis is a prerequisite first step in the development of both early diagnosis and better therapies, particularly biologic therapies. Perhaps most important, these investigators have identified a

Histologic Changes in the Ovaries of Cancer-Prone Women: an Indication of Premalignant Change?