BRCA1 Germline Mutations in Women with Uterine Papillary Serous Carcinoma
abstract & commentary
Synopsis: BRCA1 germline mutations were observed in two of nine women with uterine papillary serous carcinoma, suggesting that this tumor might be a manifestation of familial breast-ovarian cancer.
Source: Lavie O, et al. Obstet Gynecol 2000;96:28-32.
Lavie and colleagues conducted a study to determine the possible effects and incidence of BRCA1 and BRCA2 germline mutations in uterine papillary serous carcinoma (UPSC). They screened DNA from 12 women with UPSC for BRCA1 and BRCA2 germline mutations common in the Jewish population. In women with germline mutations, tumor DNA was screened for loss of heterozygosity at the appropriate loci. Nine women were of Jewish Ashkenazi origin and three were non-Ashkenazi. Two of nine Ashkenazi women were carriers of germline mutations: one 185delAG mutation and one 5382insC mutation. Five women had histories of breast carcinoma before diagnosis of UPSC. Family histories of seven women had at least one first-degree relative with malignant disease. Of those, four had at least one first-degree relative with breast, ovarian, or colon carcinoma. Both carriers had strong family histories of breast-ovarian carcinoma. Loss of heterozygosity analysis found loss of the wild-type BRCA1 allele in the primary uterine tumors. Lavie et al concluded that the loss of heterozygosity in the tumor tissue of the carriers, coupled with the high frequency of family and patient histories of breast or ovarian malignancies, suggest that UPSC might be a manifestation of familial breast-ovarian cancer.
Comment by David M. Gershenson, MD
UPSC was first described by investigators at Stanford University in 1982. UPSC accounts for approximately 5% of all endometrial cancers, and is histologically indistinguishable from papillary serous carcinoma of the ovary or peritoneum. UPSC has a much more aggressive biologic behavior than the typical endometrioid type of endometrial cancer, with a tendency to metastasize intraperitoneally. There is no standard treatment for UPSC beyond primary abdominal hysterectomy and bilateral salpingo-oophorectomy plus comprehensive surgical staging. For patients with metastatic disease, recommended treatment range from platinum-based chemotherapy to taxane-based chemotherapy to abdominopelvic radiotherapy. For patients with disease confined to the uterus, recommendations range from pelvic radiotherapy to combination chemotherapy to observation. In 1967, Dr. Henry Lynch first described the Lynch Type II syndrome, in which families had a predisposition to have members with colon, breast, ovarian, and endometrial cancers. The findings of this study suggest that UPSC may be a manifestation of BRCA1-associated familial breast-ovarian cancer syndrome. Clearly, this is a small study, and larger studies need to be conducted in the future to elucidate this issue. As Lavie et al point out, the inclusion of endometrial cancer (including UPSC) in the familial breast-ovarian cancer syndrome argues for consideration of hysterectomy in women who undergo prophylactic oophorectomy for BRCA1 or BRCA2 germline mutation.
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