313P Secretory cells expansion as a very early event in ovarian high-grade serous carcinoma

Abstract

Background Ovarian high-grade serous carcinoma (HGSC) is one of the most aggressive and widely spread gynecological tumors all over the world. We studied the incidenceofsecretorycellexpansion(SCE) andsecretorycells outgrowth (SCOUT) in the of the fallopian tube in patients with gynecological pathology, determined their immunophenotypeandbiologicalroleintheearlystagesofovarianofHGCSsearching the early diagnostic test for HGSC. Methods 287 patients with benign serous ovarian cystadenomas (n = 75), borderline serous ovarian tumors (n = 73), HGSC (n = 69) and extraovarian pathology (n = 70) were recruited, the fallopian tubes were investigated morphologically and immunohistochemically (p53, Ki-67, PAX2, bcl-2, beta-catenin, ALDH1) with semiquantative assessment (0 for negative, 1 - for weak, 2 - for moderate and 3 - for strong expression. Mann-Whitney and v2 tests was used for statistics. Results Incidenceof SCE(>10 secretorycellsinarow) andSCOUT(>30secretory cells in a row) increases with age in all groups. SCE were revealed 5.9-fold more frequent inpatients withHGSCthan in patientswithextraovarian pathology(p<0.01), while SCOUTwererevealed3.4-foldmorefrequent(p<0.05). PAX2expression innormal epitheliumwas2.8, inSCE-1.3, inSCOUT-1.2, inHGSC-0.9. bcl-2expressioninthe normalepithelium was2.2, theSCE-2.1, in SCOUT-2.2, in HGSC-0.6, beta-catenin expressioninnormalepithelium was0.5, in SCE-2.85, in SCOUT-2.95, inHGSC-0.5, ALDH1 expression innormalepitheliumwas0.5, inSCE-2.91, inSCOUT-2.92, in HGSC-0.6. Statisticallysignificantdifferences werefoundforallmarkersbetween normalepithelium, secretorycellschanges(SCEandSCOUT) andHGSC(p <0.05). Conclusions >WehaveshownthattheSCEwasanindependentintraepitheliallesions.The frequency of SCE increase with age. The difference in frequency of SCE between patients withextraovarianpathologyandHGSCwasmoresignificantthandifferenceinfrequency of SCOUT between these groups. Thus, SCE can be a more sensitive marker for the early stages of the pathogenesis of HGSC. Multiple molecular events occur in SCE and the therapeuticeffectontheearlystagesofpathogenesismayhaveseveralpointsofapplication. Legal entity responsible for the study Federal State Budget Institution “Research Center for Obstetrics, Gynecology and Perinatology” Ministry of Healthcare of the Russian Federation Funding Federal State Budget Institution “Research Center for Obstetrics, Gynecology and Perinatology” Ministry of Healthcare of the Russian Federation Disclosure All authors have declared no conflicts of interest.