Tumors of female reproductive systemTumors of female reproductive systemОпухоли женской репродуктивной системы1994-40981999-8627Publishing House ABV Press70610.17650/1994-4098-2020-16-1-78-84GYNECOLOGY. REVIEWSГИНЕКОЛОГИЯ. ОБЗОРНЫЕ СТАТЬИMorphological basics of ovarian tumor histogenesisМорфологические основы гистогенеза опухолей яичникаhttps://orcid.org/0000-0002-8902-859XNovikovF. V.НовиковФ. В.
Russian Federation

Department of Obstetrics and Gynecology,

Филипп Владимирович Новиков 

Кафедра акушерства и гинекологии

philip.novikov@mail.ruLunevaI. S.ЛунёваИ. С.
Russian Federation

Department of Obstetrics and Gynecology,

Кафедра акушерства и гинекологии

https://orcid.org/0000-0002-6021-2068

https://orcid.org/0000-0003-3835-0594MishinaE. S.МишинаЕ. С.
Russian Federation

Department of Histology, Embryology, Cytology

кафедра гистологии, эмбриологии, цитологии

https://orcid.org/0000-0001-7147-7912MnikhovichM. V.МниховичМ. В.
Russian Federation

Central Anatomicopathological Laboratory

Центральная патологоанатомическая лаборатория

Kursk State Medical University, Ministry of Health of RussiaФГБОУ ВО «Курский государственный медицинский университет» Минздрава РоссииResearch Institute of Human MorphologyФГБНУ «Научно-исследовательский институт морфологии человека»0906202016178840906202009062020https://ojrs.abvpress.ru/ojrs/article/view/706

Researches about the origin of epithelial ovarian tumors (EOT) tell about its conception. In particular, the origin of cells from the secondary mullerian system. Also, in the article we examine a new hypothesis that the EOT originates in the epithelium of the fallopian tube (FT) – their contradictoriness and new conception of “precursor escape” which tries to explain the phenomenon of injuries absence of FT by high-grade serous ovarian carcinoma. Carcinogenesis from the FT represents great opportunities for reassessment of clinical data. Also, the article represents the role of stem cells of the surface epithelium of ovaries and FT in EOT carcinogenesis.

В обзоре литературы, посвященном происхождению эпителиальных опухолей яичника (ЭОЯ), обсуждается актуальность концепций возникновения ЭОЯ, в частности из клеток вторичной мюллеровой системы. Также рассматриваются новые гипотезы происхождения ЭОЯ из эпителия фаллопиевых труб (ФТ) – их противоречивость и новая концепция «побега предшественника», претендующая на объяснение феномена отсутствия поражений ФТ при низкодифференцированной серозной адненокарциноме яичника. Канцерогенез низкодифференцированной серозной адненокарциномы яичника из ФТ представляет большие возможности для переоценки клинических данных. Также в статье раскрывается роль стволовых клеток покровного эпителия яичников и ФТ в канцерогенезе ЭОЯ.

epithelial ovarian tumorshistogenesishigh-grade serous ovarian carcinomamullerian systemfallopian tubesserous tubal intraepithelial carcinomaovarian surface epitheliumstem cellsэпителиальные опухоли яичникагистогенезнизкодифференцированная серозная адненокарцинома яичникамюллерова системафаллопиевы трубысерозная интраэпителиальная карциномапокровный эпителий яичникастволовые клеткиKurman R.J., Shih I. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer – shifting the paradigm. Hum Pathol 2011;42:918–31. DOI: 10.1016/j.humpath.2011.03.003.Kroeger P.T., Drapkin R. Pathogenesis and heterogeneity of ovarian cancer. Curr Opin Obstet Gynecol 2017;29(1):26–34. DOI: 10.1097/GCO.0000000000000340.Siegel R.L., Miller K.D., Jemal A. Cancer statistics. CA Cancer J Clin 2016;66:7–30. DOI: 10.3322/caac.21332.American Cancer Society. Cancer treatment & survivorship facts & figures 2016–2017. Atlanta, 2016.Ashrafyan L.A. Sporadic ovarian cancer: The probable model of pathogenesis. Zhurnal akusherstva i zhenskikh bolezney = Journal of Obstetrics and Women’s Diseases 2012;(4):3–10. (In Russ.). DOI: 10.17816/JOWD6143-10.Ашрафян Л.А. Спорадический рак яичников: вероятная модель патогенеза. Журнал акушерства и женских болезней 2012;(4):3–10. DOI: 10.17816/JOWD6143-10.Kurman R., Shih I. The origin and pathogenesis of epithelial ovarian cancer: A proposed unifying theory. Am J Surg Pathol 2010;34:3:433–43. DOI: 10.1097/pas.0b013e3181cf3d79.Lauchlan S.C. The secondary mullerian system revisited. Int J Gynecol Pathol 1994;13:73–9.Glazunov M.F. Ovarian tumors (morphology, histogenesis, problems of pathogenesis). Leningrad, 1954. (In Russ.).Глазунов М.Ф. Опухоли яичников (морфология, гистогенез, вопросы патогенеза). Л., 1954.Dubeau L. The cell of origin of ovarian epithelial tumours. Lancet Oncol 2008;9:191–7. DOI: 10.1016/S1470-2045(08)70308-5.Banet N., Kurman R.J. Two types of ovarian cortical inclusion cysts: proposed origin and possible role in ovarian serous carcinogenesis. Int J Gynecol Pathol 2015;34:3–8. DOI: 10.1097/PGP.0000000000000120.McCaughey W.T., Kirk M.E., Lester W. et al. Peritoneal epithelial lesions associated with proliferative serous tumours of ovary. Histopathology 1984;8:195–220.Folkins A.K., Jarboe E.A., Saleemuddin A. et al. A candidate precursor to pelvic serous cancer (p53 signature) and its prevalence in ovaries and fallopian tubes from women with BRCA mutations. Gynecol Oncol 2008;109(2):168–73. DOI: 10.1016/j.ygyno.2008.01.012.Barakat R.R., Federici M.G., Saigo P.E. et al. Absence of premalignant histologic, molecular, or cell biologic alterations in prophylactic oophorectomy specimens from BRCA1 heterozygotes. Cancer 2000; 89:383–90. DOI: 10.1002/1097-0142(20000715)89:23.0.co;2-t.Bahar-Shany K., Brand H., Sapoznik S. et al. Exposure of fallopian tube epithelium to follicular fluid mimics carcinogenic changes in precursor lesions of serous papillary carcinoma. Gynecol Oncol 2014;132:322–7. DOI: 10.1016/j.ygyno.2013.12.015.Danilova N.V., Andreeva Yu.Yu., Korolev A.V. et al. Role of dysplastic changes in the uterine tubal epithelium in the histogenesis of ovarian cancer. Arkhiv patologii = Archive of Pathology 2014;(4):9–14. (In Russ.).Данилова Н.В., Андреева Ю.Ю., Королев А.В. и др. Роль диспластических изменений эпителия маточной трубы в гистогенезе рака яичников. Архив патологии 2014;(4):9–14.Piek J.M., Verheijen R.H., Kenemans P. et al. BRCA1/2-related ovarian cancers are of tubal origin: a hypothesis. Gynecol Oncol 2003;90(2):491. DOI: 10.1016/s0090-8258(03)00365-2.Shaw P.A., Rouzbahman M., Pizer E.S. et al. Candidate serous cancer precursors in fallopian tube epithelium of BRCA1/2 mutation carriers. Mod Pathol 2009;22:1133–8. DOI: 10.1038/modpathol.2009.89.Lee Y., Miron A., Drapkin R. et al. A candidate precursor to serous carcinoma that originates in the distal fallopian tube. J Pathol 2007;211:26–35. DOI: 10.1002/path.2091.Medeiros F., Muto M.G., Lee Y. et al. The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol 2006;30:230–6. DOI: 10.1097/01.pas.0000180854.28831.77.Kindelberger D.W., Lee Y., Miron A. et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am J Surg Pathol 2007;31:161–9. DOI: 10.1097/01.pas.0000213335.40358.47.Kuhn E., Kurman R.J., Vang R. et al. TP53 mutations in serous tubal intraepithelial carcinoma and concurrent pelvic high-grade serous carcinoma – evidence supporting the clonal relationship of the two lesions. J Pathol 2012;226:421–6. DOI: 10.1002/path.3023.Tone A.A., Begley H., Sharma M. et al. Gene expression profiles of luteal phase fallopian tube epithelium from BRCA mutation carriers resemble high-grade serous carcinoma. Clin Cancer Res 2008;14(13):4067–78. DOI: 10.1158/1078-0432.CCR-07-4959.Brown P.O., Palmer C. The preclinical natural history of serous ovarian cancer: defining the target for early detection. PLoS Med 2009;6(7):e1000114. DOI: 10.1371/journal.pmed.1000114.Wheeler D.T., Bell K.A., Kurman R.J. et al. Minimal uterine serous carcinoma: diagnosis and clinicopathologic correlation. Am J Surg Pathol 2000;24:797–806.Callahan M.J., Crum C.P., Medeiros F. et al. Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction. J Clin Oncol 2007;25:3985–90. DOI: 10.1200/JCO.2007.12.2622.Yang-Hartwich Y., Gurrea-Soteras M., Sumi N. et al. Ovulation and extra-ovarian origin of ovarian cancer. Sci Rep 2014;4:6116. DOI: 10.1038/srep06116.Russo A., Czarnecki A.A., Dean M. et al. PTEN loss in the fallopian tube induces hyperplasia and ovarian tumor formation. Oncogene 2018;37:1976–90. DOI: 10.1038/s41388-017-0097-8.Rabban J.T., Garg K., Crawford B. et al. Early detection of high-grade tubal serous carcinoma in women at low risk for hereditary breast and ovarian cancer syndrome by systematic examination of fallopian tubes incidentally removed during benign surgery. Am J Surg Pathol 2014;38:729–42. DOI: 10.1097/PAS.0000000000000199.Mahe E., Tang S., Deb P. et al. Do deeper sections increase the frequency of detection of serous tubal intraepithelial carcinoma (STIC) in the “sectioning and extensively examining the FIMbriated end” (SEE-FIM) protocol? Int J Gynecol Pathol 2013;32:353–7. DOI: 10.1097/PGP.0b013e318264ae09.Carlson J.W., Jarboe E.A., Kindelberger D. et al. Serous tubal intraepithelial carcinoma: diagnostic reproducibility and its implications. Int J Gynecol Pathol 2010;29:310–4. DOI: 10.1097/PGP.0b013e3181c713a8.Visvanathan K., Vang R., Shaw P. et al. Diagnosis of serous tubal intraepithelial carcinoma based on morphologic and immunohistochemical features: a reproducibility study. Am J Surg Pathol 2011;35:1766–75. DOI: 10.1097/PAS.0b013e31822f58bc.Dehari R., Kurman R.J., Logani S. et al. The development of highgrade serous carcinoma from atypical proliferative (borderline) serous tumors and low-grade micropapillary serous carcinoma: a morphologic and molecular genetic analysis. Am J Surg Pathol 2007;31:1007–12. DOI: 10.1097/PAS.0b013e31802cbbe9.Novak M., Lester J., Karst A.M. et al. Stathmin 1 and p16 (INK4A) are sensitive adjunct biomarkers for serous tubal intraepithelial carcinoma. Gynecol Oncol 2015;139:104–11. DOI: 10.1016/j.ygyno.2015.07.100.Mehra K.K., Chang M.C., Folkins A.K. et al. The impact of tissue block sampling on the detection of p53 signatures in fallopian tubes from women with BRCA 1 or 2 mutations (BRCA+) and controls. Mod Pathol 2011;24:152–6. DOI: 10.1038/modpathol.2010.171.Soong T.R., Howitt B.E., Miron A. et al. Evidence for lineage continuity between early serous proliferations (ESPs) in the fallopian tube and disseminated highgrade serous carcinomas. J Pathol 2018;25. DOI: 10.1002/path.5145.Anglesio M.S., Bashashati A., Wang Y.K. et al. Multifocal endometriotic lesions associated with cancer are clonal and carry a high mutation burden. J Pathol 2015;236: 201–9. DOI: 10.1002/path.4516.Anglesio M.S., Wang Y.K., Maassen M. et al. Synchronous endometrial and ovarian carcinomas: evidence of clonality. J Natl Cancer Inst 2016;108(6):djv428. DOI: 10.1093/jnci/djv428.Dinulescu D.M., Ince T.A., Quade B.J. et al. Role of Kras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med 2005;11:63–70. DOI: 10.1038/nm1173.Zhordania K.I., Payanidi Yu.G., Loginov V.I. et al. Synchronous endometrioid tumors of the uterus and the ovaries. Complicacy of interpretation. Problemy reproduktsii = Russian Journal of Human Reproduction 2018;24(4):66–70. (In Russ.). DOI: 10.17116/repro20182404166.Жорданиа К.И., Паяниди Ю.Г., Логинов В.И. и др. Синхронные эндометриоидные опухоли матки и яичников. Сложности интерпретации. Проблемы репродукции 2018;24(4):66–70. DOI: 10.17116/repro20182404166.Rinda T.S., Howitt B.E., Horowitz N. et al. The fallopian tube, “precursor escape” and narrowing the knowledge gap to the origins of high-grade serous carcinoma. Gynecol Oncol 2018;152(2):426–33. DOI: 10.1016/j.ygyno.2018.11.033.Vang R., Visvanathan K., Gross A. et al. Validation of an algorithm for the diagnosis of serous tubal intraepithelial carcinoma. Int J Gynecol Pathol 2012;31:243–53. DOI: 10.1097/PGP.0b013e31823b8831.Dubeau L., Drapkin R. Coming into focus: the nonovarian origins of ovarian cancer. Ann Oncol 2013;24(Suppl 8): viii28–35. DOI: 10.1093/annonc/mdt308.Barker N., Ridgway R.A., van Es J.H. et al. Crypt stem cells as the cells-of-origi n of intestinal cancer. Nature 2009;457:608–11. DOI: 10.1038/nature07602.Zhu L., Gibson P., Currle D.S. et al. Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 2009;457:603–7. DOI: 10.1038/nature07589.Sangiorgi E., Capecchi M.R. Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet 2008;40:915–20. DOI: 10.1038/ng.165.Bapat S.A., Mali A.M., Koppikar C.B., Kurrey N.K. Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res 2005;65:3025–9. DOI: 10.1158/0008-5472.CAN-04-3931.Ng A., Tan S., Singh G. et al. Lgr5 marks stem/progenitor cells in ovary and tubal epithelia. Nat Cell Biol 2014;16:745–57. DOI: 10.1038/ncb3000.Pail D.Y., Janzen D.M., Schafenacker A.M. et al. Stem-like epithelial cells are concentrated in the distal end of the fallopian tube: a site for injury and serous cancer initiation. Stem Cells 2012;30(11):2487–97. DOI: 10.1002/stem.1207.Flesken-Nikitin A., Hwang C., Cheng C.Y. et al. Ovarian surface epithelium at the junction area contains a cancerprone stem cell niche. Nature 2013;495: 241–5. DOI: 10.1038/nature11979.Bahar-Shany K., Brand H., Sapoznik S. et al. Exposure of fallopian tube epithelium to follicular fluid mimics carcinogenic changes in precursor lesions of serous papillary carcinoma. Gynecol Oncol 2014;132:322–7. DOI: 10.1016/j.ygyno.2013.12.015.Auersperg N. The origin of ovarian carcinomas: a unifying hypothesis. Int J Gynecol Pathol 2011;30:12–21. DOI: 10.1097/PGP.0b013e3181f45f3e.Auersperg N., Woo M.M., Gilks C.B. The origin of ovarian carcinomas: a developmental view. Gynecol Oncol 2008;110:452–4. DOI: 10.1016/j.ygyno.2008.05.031.Auersperg N. The stem-cell profile of ovarian surface epithelium is reproduced in the oviductal fimbriae, with increased stem-cell marker density in distal parts of the fimbriae. Int J Gynecol Pathol 2013;32:444–53. DOI: 10.1097/PGP.0b013e3182800ad5.Asaturova A.V. Sources of highly-malignant serous ovarian carcinomas. Zlokachestvennie opukholi = Malignant Tumors 2019;(3s1):9–14. (In Russ.). DOI: 10.18027/2224-5057-2019-9-3s1-9-14.Асатурова А.В. Источники происхождения серозных карцином яичника высокой степени злокачественности. Злокачественные опухоли 2019;(3s1):9–14. DOI: 10.18027/2224-5057-2019-9-3s1-9-14.