Diagram of a fimbrial plica, illustrating the stepwise progression of normal fallopian tube epithelium to invasive serous carcinoma. The fallopian tube epithelium (FTE) is composed of a single layer of ciliated and secretory cells that are exposed to ovulation-associated inflammatory cytokines and reactive oxygen species (ROS). Repetitive genotoxic stress causes DNA damage and induces p53 mutation, leading to the clonal expansion of normal looking FTE cells of secretory phenotype. This stretch of damaged cells—termed a “p53 signature”—stains strongly for p53 and -H2AX. Further genetic “hits” enable cells to acquire a proliferative capacity, giving rise to tubal intraepithelial carcinoma (TIC). As a TIC progresses to invasive serous carcinoma, malignant cells are exfoliated from the fimbria, whereupon they may spread rapidly to the surface of the peritoneum and/or ovary. Exfoliation may also occur from TICs prior to fimbrial invasion.