Beirne JP, McArt DG, Roddy A, et al. - Since the origin of high grade serous carcinoma (HGSC) from the fallopian tube via the precursor lesion; serous tubal intraepithelial carcinoma (STIC), was strongly suggested by recent pathological evidence, researchers undertook this inquiry to more clearly define the molecular pathogenesis of HGSC. From the Northern Ireland Gynaecological Cancer Centre, 6 cases of HGSC were selected, each containing ovarian HGSC (HGSC), omental HGSC, STIC, normal fallopian tube epithelium (FTE) and normal ovarian surface epithelium (OSE). They also analyzed relevant formalin-fixed paraffin-embedded tissue samples obtained from the pathology archive through the Northern Ireland Biobank. The inquiry of HGSC carcinogenesis revealed a more close association of the molecular profile of HGSC with normal FTE vs OSE. STIC lesions also clustered closely with HGSC, suggesting a common molecular origin. Strong evidence suggestive of the origin of extrauterine HGSC from the fimbria of the distal fallopian tube was generated in this study. Various potential pathways that could be targeted by new treatments for HGSC were also described.