Microscopic and Early-Stage Ovarian Cancers in BRCA1/2 Mutation Carriers: Building a Model for Early BRCA-Associated Tumorigenesis

Possible pathways of BRCA-associated ovarian/fallopian tube cancer initiation and progression. A, some tumors begin in the fallopian tube and continue to grow larger, while remaining confined to the tube, creating a primary tubal cancer. However, because of the close association between the fimbria and ovarian surface, fallopian tube tumor cells could also spread to the ovary (B and C). B, cancer initiation occurs in the fallopian tube fimbria and a small number of cancer cells are deposited on to the ovarian surface, which provides a supportive environment for tumor growth. C, because of the cyclic rupture, repair, and invaginations that occurs with ovulation, cancer cells from the fimbria can be transferred into the ovarian stroma where it grows and expands. D, alternatively, early carcinogenic changes may occur within ovarian cysts where the tumor grows, again producing a dominant ovarian mass. As the tumor grows larger, involving both the fallopian tube and the ovaries, it becomes difficult to identify whether the site of origin was ovary or fallopian tube. OSE, ovarian surface epithelium.