The fallopian tube, “precursor escape” and narrowing the knowledge gap to the origins of high-grade serous carcinoma
If the fallopian tubes are the origin of most high-grade serous carcinomas (HGSC), why do only 30 to 40 percent of women with advanced HGSC have cancer in the fallopian tube?
HGSC is the most common histological type of ovarian cancer. Serous tubal intraepithelial carcinomas (STIC) and premalignant, early serous proliferation (ESP) are recognised as precursor lesions of HGSC. While ESPs are relatively common in the general population, most women who have them never develop ovarian cancer.
Identical somatic mutations of TP53 (a tumour suppressor gene) in HGSC, STIC and ESP lesions suggest genetic mutation as a cause. HGSC may develop due to “precursor escape,” whereby TP53-mutated tubal epithelial cells from STIC or ESP escape from the fallopian tube, as a precursor of HGSC.
This pathway to HGSC show the challenge faced in preventing or intercepting HGSCs at a curable stage. It also supports opportunistic salpingectomy in all women, especially high-risk women.
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