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Abstract & Commentary
Synopsis: Ovarian cancer diagnoses in HNPCC were typically frankly invasive, low-grade epithelial adenocarcinomas diagnosed at early stage, frequently with a synchronous endometrial cancer.
Source: Watson P, et al. Gynecol Oncol. 2001;82: 223-228.
As part of a multi-institutional study, members of the International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer (HNPCC) collected retrospective data on 90 ovarian cancer patients who were members of HNPCC families, including 31 known mutation carriers, 35 presumptive carriers (by colorectal/endometrial cancer status), and 14 at-risk family members. Data on 100 patients were submitted from 14 registries in 11 countries. The mean age at diagnosis of ovarian cancer was 42.7 years. Nonepithelial tumors constituted only 6.4% of the cancers, and borderline tumors comprised 4.1% of the epithelial cancers. Among frankly malignant epithelial cases, most cancers were well or moderately differentiated, and 85% were FIGO stage I or II at diagnosis. Synchronous endometrial cancer was reported in 21.5% of cases. Watson and colleagues concluded that ovarian cancer in HNPCC differs from ovarian cancer in the general population in several clinically important respects. It occurs at a markedly earlier age. It is more likely to be epithelial. If it is a frankly invasive epithelial cancer, it is more likely to be well or moderately differentiated. HNPCC patients with ovarian cancer are more likely to have a synchronous endometrial cancer than other ovarian cancer patients and are more likely to be diagnosed at an early stage.
Comment by David M. Gershenson, MD
HNPCC, or the Lynch syndrome, is a common hereditary cancer syndrome. The molecular basis for HNPCC is a mutation in DNA mismatch repair genes. HNPCC is associated with a significantly increased risk of colorectal cancer, which typically may occur at an early age. There is also an increased risk of other cancers, including endometrial, ovarian, gastric, small intestinal, transitional cell cancers of the genitourinary tract, skin tumor, brain tumors, and hepatobiliary tract tumors. The present paper is the most comprehensive report on ovarian cancer in HNPCC to date. Watson et al found that ovarian cancer occurring in association with HNPCC differs from typical ovarian cancer in several ways. Most important of these are the early age at diagnosis, the patterns of earlier stage and lower histologic grade, and the relatively high incidence of synchronous endometrial cancer. The major flaw in this study is the lack of central pathology review since the study spanned a 60-year-plus period. Nevertheless, it represents the best data we have thus far. The challenge for clinicians is to develop a strategy to identify members of HNPCC families and to appropriately advise them regarding their risk for multiple different malignancies and the optimal surveillance for each.