Advertisement

Of mice and women - Non-ovarian origins of “ovarian” cancer

  • Author Footnotes
    1 Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Room 3-118, Vancouver, BC V5Z 1L3, Canada.
    Anthony N. Karnezis
    Footnotes
    1 Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Room 3-118, Vancouver, BC V5Z 1L3, Canada.
    Affiliations
    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    Search for articles by this author
  • Kathleen R. Cho
    Correspondence
    Corresponding author at: Department of Pathology, University of Michigan Medical School, 1506 BSRB, 109 Zina Pitcher, Ann Arbor, MI 48109, United States.
    Affiliations
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, United States
    Search for articles by this author
  • Author Footnotes
    1 Department of Pathology and Laboratory Medicine, University of British Columbia, 675 West 10th Avenue, Room 3-118, Vancouver, BC V5Z 1L3, Canada.
Published:November 24, 2016DOI:https://doi.org/10.1016/j.ygyno.2016.11.039
      A number of recent publications have presented competing views on origins of the heterogeneous group of epithelial malignancies currently classified as ovarian carcinomas (OCs) [
      • Karnezis A.N.
      • Cho K.R.
      • Gilks C.B.
      • Pearce C.L.
      • Huntsman D.G.
      The disparate origins of ovarian cancers: pathogenesis and prevention strategies.
      ,
      • Kurman R.J.
      • Shih I.M.
      The dualistic model of ovarian carcinogenesis: revisited, revised, and expanded.
      ,
      • Cardenas C.
      • Alvero A.B.
      • Yun B.S.
      • Mor G.
      Redefining the origin and evolution of ovarian cancer: a hormonal connection.
      ,
      • Perets R.
      • Drapkin R.
      It's totally tubular…riding the new wave of ovarian cancer research.
      ,
      • Silva E.G.
      The origin of epithelial neoplasms of the ovary: an alternative view.
      ,
      • Dubeau L.
      • Drapkin R.
      Coming into focus: the nonovarian origins of ovarian cancer.
      ,
      • Auersperg N.
      The origin of ovarian cancers—hypotheses and controversies.
      ,
      • Kuhn E.
      • Kurman R.J.
      • Shih I.M.
      Ovarian cancer is an imported disease: fact or fiction?.
      ]. On one end of the spectrum, some have argued that OC is not ovarian in origin, but arises instead from Müllerian-derived extra-ovarian cells that involve the ovary secondarily. Others have been reluctant to embrace this view. Much of the debate has focused on the origin(s) of high-grade serous carcinoma (HGSC), the most common OC subtype and the one responsible for most deaths attributed to OC. While analyses of non-neoplastic and tumor tissues from women with OC, particularly those with genetic predisposition, have led to important new insights into OC origins, studies in animal model systems are beginning to shed light on questions that have been difficult to address in humans. Developing a more complete understanding of OC origins is not a purely academic exercise, but rather, can be expected to lead to more effective strategies for prevention, early detection, and treatment of OC. Here we will highlight selected studies in humans that provide insights into – and raise additional questions about – OC origins. We will also review some recent studies using genetically engineered mice that illustrate the relative influences of genetics and cells of origin on OC histopathology and biological behavior. Collectively, these studies are helping to refine current views on OC origins and to identify some of the important knowledge gaps that remain.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Gynecologic Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Karnezis A.N.
        • Cho K.R.
        • Gilks C.B.
        • Pearce C.L.
        • Huntsman D.G.
        The disparate origins of ovarian cancers: pathogenesis and prevention strategies.
        Nat. Rev. Cancer. 2016; (in press)
        • Kurman R.J.
        • Shih I.M.
        The dualistic model of ovarian carcinogenesis: revisited, revised, and expanded.
        Am. J. Pathol. 2016; 186: 733-747
        • Cardenas C.
        • Alvero A.B.
        • Yun B.S.
        • Mor G.
        Redefining the origin and evolution of ovarian cancer: a hormonal connection.
        Endocr. Relat. Cancer. 2016; 23: R411-R422
        • Perets R.
        • Drapkin R.
        It's totally tubular…riding the new wave of ovarian cancer research.
        Cancer Res. 2016; 76: 10-17
        • Silva E.G.
        The origin of epithelial neoplasms of the ovary: an alternative view.
        Adv. Anat. Pathol. 2016; 23: 50-57
        • Dubeau L.
        • Drapkin R.
        Coming into focus: the nonovarian origins of ovarian cancer.
        Ann. Oncol. 2013; 24: viii28-viii35
        • Auersperg N.
        The origin of ovarian cancers—hypotheses and controversies.
        Front. Biosci. 2013; 5: 709-719
        • Kuhn E.
        • Kurman R.J.
        • Shih I.M.
        Ovarian cancer is an imported disease: fact or fiction?.
        Curr. Obstet. Gynaecol. Rep. 2012; 1: 1-9
        • Kindelberger D.W.
        • Lee Y.
        • Miron A.
        • Hirsch M.S.
        • Feltmate C.
        • Medeiros F.
        • et al.
        Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship.
        Am. J. Surg. Pathol. 2007; 31: 161-169
        • Crum C.P.
        • Drapkin R.
        • Miron A.
        • Ince T.A.
        • Muto M.
        • Kindelberger D.W.
        • et al.
        The distal fallopian tube: a new model for pelvic serous carcinogenesis.
        Curr. Opin. Obstet. Gynecol. 2007; 19: 3-9
        • Reitsma W.
        • de Bock G.H.
        • Oosterwijk J.C.
        • Bart J.
        • Hollema H.
        • Mourits M.J.
        Support of the ‘fallopian tube hypothesis’ in a prospective series of risk-reducing salpingo-oophorectomy specimens.
        Eur. J. Cancer. 2012;
        • Shaw P.A.
        • Rouzbahman M.
        • Pizer E.S.
        • Pintilie M.
        • Begley H.
        Candidate serous cancer precursors in fallopian tube epithelium of BRCA1/2 mutation carriers.
        Mod. Pathol. 2009; 22: 1133-1138
        • Crum C.P.
        • Drapkin R.
        • Kindelberger D.
        • Medeiros F.
        • Miron A.
        • Lee Y.
        Lessons from BRCA: the tubal fimbria emerges as an origin for pelvic serous cancer.
        Clin. Med. Res. 2007; 5: 35-44
        • Callahan M.J.
        • Crum C.P.
        • Medeiros F.
        • Kindelberger D.W.
        • Elvin J.A.
        • Garber J.E.
        • et al.
        Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction.
        J. Clin. Oncol. 2007; 25: 3985-3990
        • Carcangiu M.L.
        • Peissel B.
        • Pasini B.
        • Spatti G.
        • Radice P.
        • Manoukian S.
        Incidental carcinomas in prophylactic specimens in BRCA1 and BRCA2 germ-line mutation carriers, with emphasis on fallopian tube lesions: report of 6 cases and review of the literature.
        Am. J. Surg. Pathol. 2006; 30: 1222-1230
        • Piek J.M.
        • van Diest P.J.
        • Zweemer R.P.
        • Jansen J.W.
        • Poort-Keesom R.J.
        • Menko F.H.
        • et al.
        Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer.
        J. Pathol. 2001; 195: 451-456
        • Przybycin C.G.
        • Kurman R.J.
        • Ronnett B.M.
        • Shih Ie M.
        • Vang R.
        Are all pelvic (nonuterine) serous carcinomas of tubal origin?.
        Am. J. Surg. Pathol. 2010; 34: 1407-1416
        • Gilks C.B.
        • Irving J.
        • Kobel M.
        • Lee C.
        • Singh N.
        • Wilkinson N.
        • et al.
        Incidental nonuterine high-grade serous carcinomas arise in the fallopian tube in most cases: further evidence for the tubal origin of high-grade serous carcinomas.
        Am. J. Surg. Pathol. 2015; 39: 357-364
        • Morrison J.C.
        • Blanco Jr., L.Z.
        • Vang R.
        • Ronnett B.M.
        Incidental serous tubal intraepithelial carcinoma and early invasive serous carcinoma in the nonprophylactic setting: analysis of a case series.
        Am. J. Surg. Pathol. 2015; 39: 442-453
        • Rabban J.T.
        • Garg K.
        • Crawford B.
        • Chen L.M.
        • Zaloudek C.J.
        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: 729-742
        • Singh N.
        • Gilks C.B.
        • Hirschowitz L.
        • Kehoe S.
        • McNeish I.A.
        • Miller D.
        • et al.
        Primary site assignment in tubo-ovarian high-grade serous carcinoma: consensus statement on unifying practice worldwide.
        Gynecol. Oncol. 2016; 141: 195-198
        • McDaniel A.S.
        • Stall J.N.
        • Hovelson D.H.
        • Cani A.K.
        • Liu C.-J.
        • Tomlins S.A.
        • et al.
        Next-generation sequencing of tubal intraepithelial carcinomas.
        JAMA Oncol. 2015; https://doi.org/10.1001/jamaoncol.2015.1618
        • Kommoss F.
        • Faruqi A.
        • Gilks C.B.
        • Lamshang Leen S.
        • Singh N.
        • Wilkinson N.
        • et al.
        Uterine serous carcinomas frequently metastasize to the fallopian tube and can mimic serous tubal intraepithelial carcinoma.
        Am. J. Surg. Pathol. 2016;
        • Rabban J.T.
        • Vohra P.
        • Zaloudek C.J.
        Nongynecologic metastases to fallopian tube mucosa: a potential mimic of tubal high-grade serous carcinoma and benign tubal mucinous metaplasia or nonmucinous hyperplasia.
        Am. J. Surg. Pathol. 2015; 39: 35-51
        • Reyes C.
        • Murali R.
        • Park K.J.
        Secondary involvement of the adnexa and uterine corpus by carcinomas of the uterine cervix: a detailed morphologic description.
        Int. J. Gynecol. Pathol. 2015; 34: 551-563
        • Stewart C.J.
        • Leung Y.C.
        • Whitehouse A.
        Fallopian tube metastases of non-gynaecological origin: a series of 20 cases emphasizing patterns of involvement including intra-epithelial spread.
        Histopathology. 2012; 60: E106-E114
        • Sampson J.A.
        Implantation carcinoma of the tubal mucosa secondary to carcinoma of the ovary.
        Am. J. Pathol. 1938; 14 (87): 385-420
        • Worley M.J.
        • Welch W.R.
        • Berkowitz R.S.
        • Ng S.W.
        Endometriosis-associated ovarian cancer: a review of pathogenesis.
        Int. J. Mol. Sci. 2013; 14: 5367-5379
        • Zinsser K.R.
        • Wheeler J.E.
        Endosalpingiosis in the omentum: a study of autopsy and surgical material.
        Am. J. Surg. Pathol. 1982; 6: 109-117
        • Irving J.
        • Clement P.B.
        Diseases of the peritoneum.
        in: Kurman R.J. Ellenson L.H. Ronnett B. Blaustein's Pathology of the Female Genital Tract. sixth ed. Springer, New York2011
        • Gruessner C.
        • Gruessner A.
        • Glaser K.
        • Abushahin N.
        • Laughren C.
        • Zheng W.
        • et al.
        Biomarkers and endosalpingiosis in the ovarian and tubal microenvironment of women at high-risk for pelvic serous carcinoma.
        Am. J. Cancer Res. 2014; 4: 61-72
        • McConechy M.K.
        • Ding J.
        • Senz J.
        • Yang W.
        • Melnyk N.
        • Tone A.A.
        • et al.
        Ovarian and endometrial endometrioid carcinomas have distinct CTNNB1 and PTEN mutation profiles.
        Mod. Pathol. 2014; 27: 128-134
        • Anglesio M.S.
        • Carey M.S.
        • Kobel M.
        • Mackay H.
        • Huntsman D.G.
        Clear cell carcinoma of the ovary: a report from the first Ovarian Clear Cell Symposium, June 24th, 2010.
        Gynecol. Oncol. 2011; 121: 407-415
        • Wiegand K.C.
        • Shah S.P.
        • Al-Agha O.M.
        • Zhao Y.
        • Tse K.
        • Zeng T.
        • et al.
        ARID1A mutations in endometriosis-associated ovarian carcinomas.
        N. Engl. J. Med. 2010; 363: 1532-1543
        • Jones S.
        • Wang T.L.
        • Shih Ie M.
        • Mao T.L.
        • Nakayama K.
        • Roden R.
        • et al.
        Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma.
        Science. 2010; 330: 228-231
        • Kuo K.T.
        • Mao T.L.
        • Jones S.
        • Veras E.
        • Ayhan A.
        • Wang T.L.
        • et al.
        Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma.
        Am. J. Pathol. 2009; 174: 1597-1601
        • Committee on the State of the Science in Ovarian Cancer Research BoHCS
        • Institute of Medicine
        • National Academies of Sciences, Engineering, and Medicine
        Ovarian Cancers: Evolving Paradigms in Research and Care.
        National Academy of Sciences, 2016
        • Szabova L.
        • Yin C.
        • Bupp S.
        • Guerin T.M.
        • Schlomer J.J.
        • Householder D.B.
        • et al.
        Perturbation of Rb, p53, and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer.
        Cancer Res. 2012; 72: 4141-4153
        • Chandler R.L.
        • Damrauer J.S.
        • Raab J.R.
        • Schisler J.C.
        • Wilkerson M.D.
        • Didion J.P.
        • et al.
        Coexistent ARID1A–PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling.
        Nat. Commun. 2015; 6: 6118
        • Kim J.
        • Coffey D.M.
        • Ma L.
        • Matzuk M.M.
        The ovary is an alternative site of origin for high-grade serous ovarian cancer in mice.
        Endocrinology. 2015; : en20141977
        • Perets R.
        • Wyant G.A.
        • Muto K.W.
        • Bijron J.G.
        • Poole B.B.
        • Chin K.T.
        • et al.
        Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca;Tp53;Pten models.
        Cancer Cell. 2013; 24: 751-765
        • Kim J.
        • Coffey D.M.
        • Creighton C.J.
        • Yu Z.
        • Hawkins S.M.
        • Matzuk M.M.
        High-grade serous ovarian cancer arises from fallopian tube in a mouse model.
        Proc. Natl. Acad. Sci. U. S. A. 2012;
        • Wu R.
        • Hendrix-Lucas N.
        • Kuick R.
        • Zhai Y.
        • Schwartz D.R.
        • Akyol A.
        • et al.
        Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/β-catenin and PI3K/Pten signaling pathways.
        Cancer Cell. 2007; 11: 321-333
        • Wu R.
        • Zhai Y.
        • Kuick R.
        • Karnezis A.N.
        • Garcia P.
        • Naseem A.
        • et al.
        Impact of oviductal versus ovarian epithelial cell of origin on ovarian endometrioid carcinoma phenotype in the mouse.
        J. Pathol. 2016; 240: 341-351