Is uterine serous papillary carcinoma a BRCA1-related disease? Case report and review of the literature.

Type II endometrial carcinomas are estrogen-independent and have adverse histologic features and a substantially poorer prognosis. No risk factors have been identified. Interestingly, there is a striking clinical and histopathological similarity between serous papillary carcinomas of the ovary (OSPC), endometrium, and peritoneal cavity, suggesting a common oncogenic mechanism. Several common molecular alterations were found using molecular comparative analysis of OSPC and uterine serous papillary carcinoma (USPC). Germline mutations in the BRCA1 tumor suppressor gene predispose to breast and ovarian cancer but no association with sporadic endometrial cancer has been found. A family of Ashkenazi Jewish origin, in which one sister was first diagnosed with USPC and the second diagnosed with OSPC, led to the hypothesis that a BRCA mutation may contribute to USPC. Genomic DNA from both patients as well as two unaffected siblings was analyzed for the three mutations common in Ashkenazi Jews. Loss of heterozygosity (LOH) analysis was performed on DNA extracted from USPC tumor tissue. Both affected sisters tested positive for BRCA1 5382insC germline mutation. LOH analysis confirmed the results. We present a breast-ovarian cancer family including two sisters with advanced serous papillary carcinomas of endometrial and ovarian origins, carrying the same BRCA1 mutation (5382insC). LOH analysis on USPC tumor DNA showed loss of the wild-type allele, suggesting a causal relationship between the germline BRCA1 mutation and USPC. We believe a study examining BRCA1 mutations in a large cohort of women with this high-risk endometrial carcinoma is warranted. A positive finding may have implications for surveillance and prophylactic surgery in carriers of BRCA1 mutations.

Hornreich G ，Beller U ，Lavie O ，Renbaum P ，Cohen Y ，Levy-Lahad E ... -  《GYNECOLOGIC ONCOLOGY》

BRCA germline mutations in Jewish women with uterine serous papillary carcinoma.

Lavie O ，Hornreich G ，Ben-Arie A ，Rennert G ，Cohen Y ，Keidar R ，Sagi S ，Lahad EL ，Auslander R ，Beller U ... -  《GYNECOLOGIC ONCOLOGY》

High incidence of BRCA1-2 germline mutations, previous breast cancer and familial cancer history in Jewish patients with uterine serous papillary carcinoma.

Biron-Shental T ，Drucker L ，Altaras M ，Bernheim J ，Fishman A ... -  《EJSO》

BRCA2 germline mutation in a woman with uterine serous papillary carcinoma--case report.

Lavie O ，Ben-Arie A ，Pilip A ，Rennert G ，Cohen Y ，Feiner B ，Auslnader R ... -  《GYNECOLOGIC ONCOLOGY》

Is uterine papillary serous adenocarcinoma a manifestation of the hereditary breast-ovarian cancer syndrome?

Uterine papillary serous carcinoma (UPSC) shares common pathologic, genetic, and clinical features with other serous cancers of müllerian origin. The most common histologic type of ovarian tumor associated with BRCA mutations is papillary serous. Because of these histologic similarities, we postulated that, in some cases, UPSC may be a manifestation of a field defect in BRCA1 carriers, which also includes ovarian carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. Fifty-six living patients with UPSC were contacted through their treating physicians and agreed to a family history interview and to provide a blood specimen for BRCA testing. The protein truncation test was used to detect mutations in exons 10 and 11 of BRCA1 and in exon 11 of BRCA2. The presence of four common mutations was assessed by PCR-based specific assays. A high proportion of patients had a past history of breast cancer (11%) or a first-degree relative with breast cancer (29%). Four patients were from families with site-specific hereditary breast cancer. However, there was no clear example of the hereditary breast-ovarian cancer syndrome, and none of the 56 patients was found to carry a BRCA1 or BRCA2 mutation. BRCA mutations do not appear to predispose to UPSC and this type of cancer does not appear to be a manifestation of the classical hereditary breast-ovarian cancer syndrome. The observed association between UPSC and breast cancer may be due to the presence of mutations in other cancer predisposing genes.

Goshen R ，Chu W ，Elit L ，Pal T ，Hakimi J ，Ackerman I ，Fyles A ，Mitchell M ，Narod SA ... -  《-》