Issues

Recent studies suggest that the fimbriated end of fallopian tube (FT) harbors the precursor for the majority of high-grade serous ovarian cancers. The initial events in FT carcinogenesis are thought to involve the accumulation of mutant p53 protein in PAX8+ secretory cells leading to the “p53 signature,” the earliest putative cancer precursor lesion detected in the fimbria. Subsequent acquisition of secondary genomic alterations leads to the development of serous tubal intraepithelial carcinoma (STIC), which spreads via shedding/exfoliation directly to the adjacent ovary and into the abdominal cavity. A growing body of compelling preclinical evidence supports progestins as ovarian cancer preventives, but the biologic effect of progestins on the FT has not been well-characterized. In a study starting on page 75, using the mogp-TAg fallopian tube cancer mouse model, Nelson and colleagues demonstrate marked inhibition of carcinogenesis in the FT by administration of a progestin. Additionally, progestin treatment markedly cleared p53-positive cells in the FT, suggesting that progestins may be targeting the earliest transformative genetic alterations in the FT. These data further support progestins as ovarian cancer preventives. The cover immunofluorescence image of a human fimbria shows co-localization of p53 and PAX8 proteins in a STIC lesion.