CORRESPONDENCE

Is Systemic Disease in the Coelomic Epithelium Associated With BRCA1 Germline Mutations?

Patricia Pautier, Philippe Morice, Suzette Delaloge, Brigitte Bressac-de Paillerets, Alain Spatz

Affiliations of authors: Department of Medical Oncology (PP, SD), Department of Surgery (PM), Unit of Genetics (BBP), Department of Pathology (AS), Institut Gustave-Roussy, Villejuif Cedex, France

Correspondence to: Patricia Pautier, MD, Service de Gynécologie Médicale, Institut Gustave-Roussy, 39 rue Camille-Desmoulins, 94805 Villejuif Cedex, France (e-mail: pautier{at}igr.fr)

Although most ovarian cancers associated with germline mutations in BRCA1 have serous or endometrial histology, other types of ovarian tumors, including mucinous and transitional cell ovarian tumors, have been described (1,2). However, only two cases of malignant ovarian transitional cell tumors have been reported so far that are associated with mutations in BRCA1 (i.e., 1136insA and 5382insC mutations) (3,4). Here, we report two new cases of malignant ovarian transitional cell tumors in patients carrying germline mutations in BRCA1. Neither patient had a history of other carcinomas. However, both patients had family histories of ovarian and/or breast cancer. Patient 1 had two first-degree relatives with breast cancer, and patient 2 had two first-degree relatives and one second-degree relative with breast cancer and one second-degree relative with ovarian cancer. We were unable to obtain the histologic reports for the family members.

Patient 1 (aged 43 years) presented with a stage IIB ovarian carcinoma [staged according to the International Federation of Gynecology and Obstetrics (5)]. She had a mutation in exon 11 of BRCA1 that resulted in a C-to-T substitution at nucleotide 1806, which led to the Q563X nonsense mutation. The histologic examination revealed an undifferentiated transitional cell carcinoma of the ovary. There was no associated urothelial tumor. Patient 2 (aged 41 years) presented with a stage IIIC ovarian carcinoma. She had a mutation in exon 5 of BRCA1 that resulted in an A-to-G substitution at nucleotide 330, which led to an R71G mutation. Histologic examination revealed a poorly differentiated carcinoma with transitional characteristics that are typically associated with Brenner tumors, which are benign ovarian tumors that are thought to be derived from the pluripotent coelomic epithelium (6).

In breast cancer, tumor differentiation is related to genetic status, i.e., breast tumors in women with germline BRCA1 mutations are more likely to be estrogen receptor–negative, progesterone receptor–negative, HER-2–negative, and have mutations in tp53 than sporadic breast tumors in women without germline BRCA1 mutations. It has been assumed that the differentiation of ovarian tumors is not related to BRCA1 mutation status because hereditary and sporadic ovarian tumors have been reported to be histologically similar and to have a similar histogenesis (2). No malignant tumors of the urothelial epithelium have been reported to be linked to a BRCA1 or BRCA2 gene mutation. Our description of two cases of malignant Brenner tumors in patients with BRCA1 mutations suggests that a systemic disease of coelomic epithelium may be associated with BRCA1 mutations. This hypothesis could explain why peritoneal carcinomas and other epithelial ovarian tumors, such as Brenner tumors, are sometimes associated with BRCA1 mutations.

REFERENCES

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2 Boyd J, Sonoda Y, Federici MG, Bogomolniy F, Rhei E, Maresco DL, et al. Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA 2000; 283: 2260–5.[Abstract/Free Full Text]

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6 Shevchuk MM, Fenoglio CM, Richart RM. Histogenesis of Brenner tumors, I: histology and ultrastructure. Cancer 1980; 46: 2607–16.[ISI][Medline]



             
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