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PhD ceremony Ms. W. Reitsma: Pelvic high-grade serous carcinoma in women with a BRCA1/2 mutation. Carcinogenesis and early diagnosis

When:We 15-05-2013 at 16:15

PhD ceremony: Ms. W. Reitsma, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Pelvic high-grade serous carcinoma in women with a BRCA1/2 mutation. Carcinogenesis and early diagnosis

Promotor(s): prof. M.J.E. Mourits, prof. G.H. de Bock, prof. H. Hollema

Faculty: Medical Sciences

Epithelial ovarian cancer is the second most common gynecological malignancy and the deadliest in terms of absolute figures. Women with a mutation in the BRCA1 or BRCA2 gene have an increased lifetime risk to develop ovarian cancer.

A nationwide study was performed to gain more insight in the tumor and survival characteristics of ovarian cancer in BRCA1 or BRCA2 mutation carriers. Results showed a significant longer progression-free and overall survival in ovarian cancer patients with a BRCA2 mutation compared to a BRCA1 mutation. These results may have implications for future studies involving new chemotherapeutic strategies for ovarian cancer.

Seventy-five percent of the ovarian cancer cases involves the aggressive high-grade serous subtype, currently known as pelvic high-grade serous cancer (PHGSC). The cell of origin of PHGSC remains unclear. To further the debate, the prevalence of precursor lesions and early development of PHGSC were investigated. We emphasize that a precursor of PHGSC has never been found in the ovary itself. However, we did find precursor lesions of PHGSC in the distal fallopian tube, called serous tubal intraepithelial carcinoma, which appoints the fallopian tube as presumed tissue of origin of PHGSC. In addition, we demonstrated that BRCA1 and BRCA2 mutation carriers have no increased risk of developing endometrial cancer.

Finally, we investigated the expression of microRNAs. The results show that a panel of microRNAs is aberrantly expressed in PHGSC in comparison to normal fallopian tube tissue, in BRCA1 mutation carriers. Further research into the significance of microRNAs for the early detection of PHGSC is therefore potentially promising.

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