Expansion of secretory cells in the fallopian tubal epithelium in the early stages of the pathogenesis of ovarian serous carcinomas

Abstract

SCE was shown to be an independent intraepithelial lesion. The incidence of this abnormality increased with age and significantly differed in the patients with fallopian tubal lesions in extraovarian diseases from that in those with malignant ovarian serous tumors (by 5.3 times), while these groups showed a three-fold difference in SCO. Thus, SCP may serve as a more sensitive marker for the early stages of the pathogenesis of ovarian serous carcinoma. The studied types of SCE demonstrated multiple molecular events (loss of PAX2 expression and increased Bcl-2, beta-catenin, and ALDH1 expressions), some of which underwent considerable changes, by increasing the severity of a pathological process (loss of ALDH1, and beta-catenin, and bcl-2 expressions). Thus, therapeutic exposure in the early stages of pathogenesis may have a few points of application and just several molecules can serve as independent markers for early pathological changes in the fallopian tubal epithelium.

Focal Serous Tubal Intra-Epithelial Carcinoma Lesions Are Associated With Global Changes in the Fallopian Tube Epithelia and Stroma

“…Until recently, only STIC lesions were considered to be bona fide early precursors to HGSOC because of the existence of matching STIC and HGSOC site-specific TP53 mutations which strongly suggested the same lineage identity ( 20 ). However, the recent discovery of matching site-specific TP53 mutations between other ESPs and HGSOC as well as associations between ESPs and the increased risk of HGSOC ( 3 , 22 , 23 ) led to the “precursor escape” theory in which ESPs undergo malignant transformation after shedding into the peritoneal cavity, thus bypassing the formation of STIC lesions in the fallopian tube as a required intermediate step to HGSOC ( 24 ). Genomic profiling did not reveal significant differences between HGSOC with and without STIC lesions ( 10 ).…”

“…Initially, only STIC lesions were thought to be the true fallopian tube precursor to HGSOC as they have similar morphologic and molecular features ( 19 – 21 ). However, ovarian cancer risk has been associated with other potential early serous precursors (ESPs) that have a benign appearance and a low proliferative index and do not satisfy the criteria of a STIC diagnosis ( 3 , 9 , 22 – 24 ). These ESPs include: serous tubal intraepithelial lesions (STIL) ( 17 ), which are characterized by lower Ki67 positivity and less cytologic atypia than STIC ( 16 , 18 ), p53 signatures defined as a single layer of >12 consecutive secretory cells with aberrant p53 expression ( 7 , 25 , 26 ), benign secretory cell outgrowth (SCOUT) defined as a continuous run of >30 secretory cells ( 3 , 5 , 9 , 22 , 23 , 27 ), and secretory cell expansion (SCE) defined as a continuous run of >10 secretory cells with normal p53 expression ( 3 , 22 , 23 ).…”

Comparative anatomy of the uterine tube of human and laboratory white rat females

“…The role of cilia is most pronounced in the ampulla of the uterine tube, where the thickness of the subserosa is up to five times smaller than the isthmus [6,13]. According to many authors, the contraction of the subserosa help to captures the egg by fimbriae [2,4,19]. Other authors believe that the frequency of cilia movement influences the speed of movement of the egg and the embryo [8,16,22].…”