BRCA1 germline mutations in women with uterine serous papillary carcinoma

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Abstract

Objective: To determine the possible effects and incidence of BRCA1 and BRCA2 germline mutations in uterine serous papillary carcinoma.

Methods: We screened DNA from 12 women with uterine serous papillary carcinoma for BRCA1 and BRCA2 germline mutations common in the Jewish population (BRCA1–185delAG and 5382insC, BRCA2–6174delT). In women with germline mutations, tumor DNA was screened for loss of heterozygosity at the appropriate loci.

Results: 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 uterine serous papillary carcinoma. 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.

Conclusion: BRCA1 germline mutations were observed in two of nine of the women in this series. 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 uterine serous papillary carcinoma might be a manifestation of familial breast-ovarian cancer.

Section snippets

Materials and methods

We reviewed all cases that fulfilled the International Federation of Gynecology and Obstetrics pathologic criteria for uterine serous papillary carcinoma, treated at either the Shaare Zedek Medical Center or Kaplan Medical Center between September 1994 and February 1999. Written informed consent was obtained for collection of epidemiologic information and blood samples. Participants received genetic counseling at their respective institutions. Information on ethnic backgrounds and medical and

Results

Twelve cases that met pathologic criteria for uterine serous papillary carcinoma were identified. The average age of the study population was 67.8 years (range 56–77 years). Women were diagnosed at advanced stages (IIB–IV), with grades 2 to 3 tumors. Nine of 12 women were of Ashkenazi origin and the three others were of Iraqi origin. Five of 12 had histories of breast cancer, diagnosed 1–14 years earlier. Eight of 12 had family histories of cancer (family history was defined as either personal

Discussion

Uterine serous papillary carcinoma is a histologic subtype of endometrial adenocarcinoma that shares morphologic and biochemical features with ovarian papillary serous carcinoma. Both neoplasms have aggressive biologic behavior and are diagnosed typically at advanced stages. In Israel, 30% of ovarian cancers in Ashkenazi Jews are associated with one of the three common BRCA1 and BRCA2 mutations.19, 20 BRCA1 germline mutations were recently associated with primary peritoneal serous papillary

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    Supported in part by a grant from the Israel Cancer Research Fund and by a gift from the Basker family, in loving memory of Eileen Basker.

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