|The following article features coverage from the Society of Gynecologic Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Results of a study comparing immunohistochemical and transcriptomic analyses of specimens of normal fallopian tube fimbriae from women with and without a germline BRCA1 mutation identified a potential precursor of cellular transformation. These findings were accepted for presentation at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer and released on March 28, 2020.
Emerging evidence supports the fallopian tubes as a site of origin for many ovarian cancers, particularly high-grade serous ovarian cancer, a common and aggressive histologic subtype of epithelial ovarian cancer that is also associated with the presence of deleterious germline BRCA mutations.2
The aim of this study was to identify potential molecular predictors of transformation of the secretory epithelium of the fallopian tube fimbriae in carriers of a germline BRCA1 mutation.
Tissue sections from the fimbriae of normal fallopian tubes from 38 women with and 36 women without a deleterious germline BRCA1 mutation were stained for PAX8 and FOXJ1, markers of secretory cells and ciliated cells, respectively, and these specimens were also analyzed by RNA sequencing.
In women with a germline BRCA1 mutation, 2 subgroups were evident based on the PAX8/FOXJ1 cell ratio. One subgroup of carriers, seen in 70% of these patients, resembled the ratio found in women without a BRCA1 mutation (ie, noncarriers), and another subgroup, observed for the remaining 30% of women, included patients that had a higher PAX8/FOXJ1 cell ratio. The presence of these 2 subgroups was particularly evident in fallopian tube fimbriae specimens from postmenopausal women.
Furthermore, signaling pathways associated with ovarian cancer, including those related to RAS, as well as the JAK/STAT3 pathway, were enriched in the fimbriae of postmenopausal women characterized by a higher PAX8/FOXJ1 ratio.
In summarizing the findings of this study, the study authors noted that “the PAX8/FOXJ1 cell ratio demarcates a unique population of postmenopausal BRCA1 mutation carriers in which cancer-related gene sets emerge in healthy tubal fimbria. Further investigation is needed to determine whether these represent the earliest stages of cancerous transformation in hereditary ovarian cancer patients.”
Read more of Cancer Therapy Advisor‘s coverage of SGO 2020 by visiting the conference page.
- Raz Y, Trabert B, Taylor-Harding B, et al. Histopathological characterization of the tubal fimbria reveals a subgroup of BRCA1 mutation carriers with tumor-promoting gene-set enrichment. Submitted to: Society of Gynecologic Oncology (SGO) 2020 Annual Meeting on Women’s Cancer. Abstract 56.
- George SHL, Garcia R, Slomovitz BM. Ovarian cancer: The fallopian tube as the site of origin and opportunities for prevention. Front Oncol. 2016;6:108.