Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-27T19:44:15.769Z Has data issue: false hasContentIssue false
  • English
  • Français

The heterogeneity of epithelial ovarian cancers: reconciling old and new paradigms

Published online by Cambridge University Press:  04 May 2007

Honami Naora
Honami Naora
Affiliation:
University of Texas M.D. Anderson Cancer Center, Department of Molecular Therapeutics, Unit 950, 7435 Fannin Street, South Campus Research Building II, Room 3.2028, Houston, TX 77054, USA. Tel: +1 713 563 4222; Fax: +1 713 563 4235; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Epithelial ovarian cancer comprises several subtypes of tumours that exhibit diverse histopathological features. The intriguing assumption by many epithelial ovarian cancers of specialised features of nonovarian tissue lineages has promoted considerable debate as to whether these tumours arise from the deceptively simple surface epithelium of the ovary. This review focuses on recent molecular and pathological studies of epithelial ovarian cancers that support and challenge their surface-epithelial derivation, and discusses the findings in the context of current views of the ‘cell-of-origin’ of solid tumours.

Type
Research Article
Information
Expert Reviews in Molecular Medicine , Volume 9 , Issue 13 , May 2007 , pp. 1 - 12
Copyright
Copyright © Cambridge University Press 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Jemal, A. et al. (2007) Cancer statistics, 2007. CA Cancer J Clin 57, 43-66Google Scholar
2BastR.C., Jr. R.C., Jr. et al. (2005) New tumor markers: CA125 and beyond. Int J Gynecol Cancer 15 (Suppl 3), 274-281Google Scholar
3Clements, P.B. and Young, R.H., eds (2000) Atlas of Gynecologic Surgical Pathology, W.B. Saunders, PhiladelphiaGoogle Scholar
4Seidman, J.D. et al. (2004) The histologic type and stage distribution of ovarian carcinomas of surface epithelial origin. Int J Gynecol Pathol 23, 41-44CrossRefGoogle ScholarPubMed
5Young, R.H. and Scully, R.E. (2001) Differential diagnosis of ovarian tumors based primarily on their patterns and cell types. Semin Diag Pathol 18, 161-235Google Scholar
6Kaku, T. et al. (2003) Histological classification of ovarian cancer. Med Electron Microsc 36, 9-17Google Scholar
7Auersperg, N. et al. (1994) Characterization of cultured human ovarian surface epithelial cells: phenotypic plasticity and premalignant changes. Lab Invest 71, 510-518Google Scholar
8Auersperg, N. et al. (2001) Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev 22, 255-288Google ScholarPubMed
9Feeley, K.M. and Wells, M. (2001) Precursor lesions of ovarian epithelial malignancy. Histopathology 38, 87-95Google Scholar
10Maines-Bandiera, S.L. and Auersperg, N. (1997) Increased E-cadherin expression in ovarian surface epithelium: an early step in metaplasia and dysplasia? Int J Gynecol Pathol 16, 250-255Google Scholar
11Davies, B.R., Worsley, S.D. and Ponder, B.A.J. (1998) Expression of E-cadherin, alpha-catenin, and beta-catenin in normal ovarian surface epithelium and epithelial ovarian cancers. Histopathology 32, 69-80Google Scholar
12Inoue, M. et al. (1992) Expression of E-cadherin in normal, benign, and malignant tissues of female genital organs. Anat Pathol 98, 76-80Google ScholarPubMed
13Sundfeldt, K. et al. (1997) E-cadherin expression in human epithelial ovarian cancer and normal ovary. Int J Cancer 74, 275-280Google Scholar
14Birchmeier, W. and Behrens, J. (1994) Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta 1198, 11-26Google Scholar
15Thiery, J.P. (2002) Epithelial-mesenchymal transitions in tumor progression. Nat Rev Cancer 2, 442-454CrossRefGoogle Scholar
16Kobayashi, A. and Behringer, R.R. (2003) Developmental genetics of the female reproductive tract in mammals. Nat Rev Genet 4, 969-980Google Scholar
17Guioli, S., Sekido, R. and Lovell-Badge, R. (2007) The origin of the Mullerian duct in chick and mouse. Dev Biol 302, 389-398Google Scholar
18Mittal, K.R. et al. (1993) Contralateral ovary in unilateral ovarian carcinoma: a search for preneoplastic lesions. Int J Gynecol Pathol 12, 59-63CrossRefGoogle ScholarPubMed
19Tresserra, F. et al. (1998) Histological features of the contralateral ovary in patients with unilateral ovarian cancer: a case control study. Gynecol Oncol 71, 437-441Google Scholar
20Salazar, H. et al. (1996) Microscopic benign and invasive malignant neoplasms and a cancer-prone phenotype in prophylactic oophorectomies. J Natl Cancer Inst 88, 1810-1820Google Scholar
21Piek, J.M.J., Kenemans, P. and Verheijen, R.H.M. (2004) Intraperitoneal serous adenocarcinoma: a critical appraisal of three hypotheses on its cause. Am J Obstet Gynecol 191, 718-732Google Scholar
22Crum, C.P. et al. (2007) The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol 19, 3-9CrossRefGoogle ScholarPubMed
23Colgan, T.J. et al. (2001) Occult carcinoma in prophylactic oophorectomy specimens. Prevalence and association with BRCA germline mutation status. Am J Surg Pathol 25, 1283-1289Google Scholar
24Paley, P.J. et al. (2001) Occult cancer of the fallopian tube in BRCA1 germline mutation carriers at prophylactic oophorectomy: a case for recommending hysterectomy at surgical prophylaxis. Gynecol Oncol 80, 176-180Google Scholar
25Lee, Y. et al. (2007) A candidate precursor to serous carcinoma that originates in the distal fallopian tube. J Pathol 211, 26-35Google Scholar
26Young, R.H., Gilks, C.B. and Scully, R.E. (1991) Mucinous tumors of the appendix associated mucinous tumors of the ovary and pseudomyxoma peritonei. A clinicopathological analysis of 22 cases supporting an origin in the appendix. Am J Surg Pathol 15, 415-429Google Scholar
27Dubeau, L. (1999) The cell of origin of ovarian epithelial tumors and the ovarian surface epithelium dogma: does the emperor have no clothes? Gynecol Oncol 72, 437-442Google Scholar
28Sainz de la Cuesta, R. et al. (1996) Histologic transformation of benign endometriosis to early epithelial ovarian cancer. Gynecol Oncol 60, 238-244Google Scholar
29Ogawa, S. et al. (2000) Ovarian endometriosis associated with ovarian carcinoma: a clinicopathological and immunohistochemical study. Gynecol Oncol 77, 298-304Google Scholar
30Prowse, A.H. et al. (2006) Molecular genetic evidence that endometriosis is a precursor of ovarian cancer. Int J Cancer 119, 556-562Google Scholar
31Sato, N. et al. (2000) Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid and clear cell carcinoma of the ovary. Cancer Res 60, 7052-7056Google Scholar
32Dinulescu, D.M. et al. (2005) Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med 11, 63-70Google Scholar
33Vercellini, P. et al. (1994) Analysis of p53 and ras gene mutations in endometriosis. Gynecol Obstet Invest 38, 70-71Google Scholar
34Connolly, D.C. et al. (2003) Female mice chimeric for expression of the simian virus 40 TAg under control of the MISIIR promoter develop epithelial ovarian cancer. Cancer Res 63, 1389-1397Google Scholar
35Flesken-Nikitin, A. et al. (2003) Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium. Cancer Res 63, 3459-3463Google Scholar
36Orsulic, S. et al. (2002) Induction of ovarian cancer by defined multiple genetic changes in a mouse model system. Cancer Cell 1, 53-62Google Scholar
37Schwartz, D.R. et al. (2002) Gene expression in ovarian cancer reflects both morphology and biological behavior, distinguishing clear cell from other poor-prognosis ovarian carcinomas. Cancer Res 62, 4722-4729Google Scholar
38Lu, K.H. et al. (2004) Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis. Clin Cancer Res 10, 3291-3300Google Scholar
39Zorn, K.K. et al. (2005) Gene expression profiles of serous, endometrioid and clear cell subtypes of ovarian and endometrial cancer. Clin Cancer Res 11, 6422-6430CrossRefGoogle ScholarPubMed
40Heinzelmann-Schwarz, V.A. et al. (2006) A distinct molecular profile associated with mucinous epithelial ovarian cancer. Br J Cancer 94, 904-913Google Scholar
41Shih, I.M. and Kurman, R.J. (2004) Ovarian tumorigenesis: A proposed model based on morphological and molecular genetic analysis. Am J Pathol 164, 1511-1518Google Scholar
42Singer, G. et al. (2003) Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst 95, 484-486Google Scholar
43Enomoto, T. et al. (1991) K-ras activation occurs frequently in mucinous adenocarcinomas and rarely in other common epithelial tumors of the ovary. Am J Pathol 139, 777-785Google Scholar
44Obata, K. et al. (1998) Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors. Cancer Res 58, 2095-2097Google ScholarPubMed
45Palacios, J. and Gamallo, C. (1998) Mutations in the beta-catenin gene (CTNNB1) in endometrioid ovarian carcinomas. Cancer Res 58, 1344-1347Google Scholar
46Tashiro, H. et al. (1997) Mutations in PTEN are frequent in endometrioid carcinoma but rare in other common gynecological malignancies. Cancer Res 57, 3935-3940Google Scholar
47Lax, S.F. et al. (2000) The frequency of p53, K-ras mutations and microsatellite instability differs in uterine endometrioid and serous carcinoma. Cancer 88, 814-824Google Scholar
48Auersperg, N. and Roskelley, C. (1991) Retroviral oncogenes: interrelationships between neoplastic transformation and cell differentiation. Crit Rev Oncog 2, 125-160Google Scholar
49Hoffman, A.G. et al. (1993) An in vitro model of ovarian epithelial carcinogenesis: Changes in cell-cell communication and adhesion occurring during neoplastic progression. Int J Cancer 54, 828-838Google Scholar
50Zheng, J. et al. (1995) Genetic disparity between morphologically benign cysts contiguous to ovarian carcinomas and solitary cystadenomas. J Natl Cancer Inst 87, 1146-1153Google Scholar
51Cheng, E.J. et al. (2004) Molecular genetic analysis of ovarian serous cystadenomas. Lab Invest 84, 778-784Google Scholar
52Mark, M., Rijli, F.M. and Chambon, P. (1997) Homeobox genes in embryogenesis and pathogenesis. Pediatr Res 42, 421-429Google Scholar
53Pearson, J.C., Lemons, D. and McGinnis, W. (2005) Modulating HOX gene functions during animal body patterning. Nat Rev Genet 6, 893-904Google Scholar
54Gehring, W.J. and Hiromi, Y. (1986) Homeotic genes and the homeobox. Annu Rev Genet 20, 147-173Google Scholar
55Taylor, H.S., Vanden Heuvel, G.B. and Igarashi, P. (1997) A conserved Hox axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the Hoxa cluster genes. Biol Reprod 57, 1338-1345Google Scholar
56Cheng, W. et al. (2005) Lineage infidelity of epithelial ovarian cancers is controlled by HOX genes that specify regional identity in the reproductive tract. Nat Med 11, 531-537Google Scholar
57Benson, G.V. et al. (1996) Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression. Development 122, 2687-2696Google Scholar
58Gendron, R.L. et al. (1997) Abnormal uterine stromal and glandular function associated with maternal reproductive defects in Hoxa-11 null mice. Biol Reprod 56, 1097-1105Google Scholar
59Fraggetta, F. et al. (2003) CDX2 immunoreactivity in primary and metastatic ovarian mucinous tumors. Virch Arch 443, 782-786Google Scholar
60Groisman, G.M., Meir, A. and Sabo, E. (2003) The value of Cdx2 immunostaining in differentiating primary ovarian carcinomas from colonic carcinomas metastatic to the ovaries. Int J Gynecol Pathol 23, 52-57Google Scholar
61Naora, H. (2005) Developmental patterning in the wrong context. The paradox of epithelial ovarian cancers. Cell Cycle 4, 1033-1035Google Scholar
62Li, C.I., Uribe, D.J. and Daling, J.R. (2005) Clinical characteristics of different histologic types of breast cancer. Br J Cancer 93, 1046-1052Google Scholar
63Bonnet, D. and Dick, J.E. (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3, 730-737Google Scholar
64Al-Hajj, M. et al. (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100, 3983-3988CrossRefGoogle ScholarPubMed
65Singh, S.K. et al. (2004) Identification of human brain tumor initiating cells. Nature 432, 396-401Google Scholar
66Bapat, S.A. et al. (2005) Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res 65, 3025-3029Google Scholar
67Szotek, P.P. et al. (2006) Ovarian cancer side population defines cells with stem cell-like characteristics and Müllerian inhibiting substance responsiveness. Proc Natl Acad Sci U S A 103, 11154-11159Google Scholar
68Pardal, R., Clarke, M.F. and Morrison, S.J. (2003) Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 3, 895-902Google Scholar
69Sell, S. (2004) Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol 51, 1-28Google Scholar
70Miller, S.J., Lavker, R.M. and Sun, T-T. (2005) Interpreting epithelial cancer biology in the context of stem cells: Tumor properties and therapeutic implications. Biochim Biophys Acta 1756, 25-52Google Scholar
71Karlan, B.Y. et al. (1995) Steroid hormone effects on the proliferation of human ovarian surface epithelial cells in vitro. Am J Obstet Gynecol 173, 97-104Google Scholar
72Burleson, K.M. et al. (2004) Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers. Gynecol Oncol 93, 170-181Google Scholar
73Fidler, I.J. (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 3, 453-458Google Scholar
74Pantel, K. and Brackenhoff, R.H. (2004) Dissecting the metastatic cascade. Nat Rev Cancer 4, 448-456Google Scholar
75Naora, H. and Montell, D.J. (2005) Ovarian cancer metastasis: Integrating insights from disparate model organisms. Nat Rev Cancer 5, 355-366Google Scholar
76Wu, R. et al. (2007) Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/beta-Catenin and PI3K/Pten signaling pathways. Cancer Cell 11, 321-333Google Scholar

Further reading, resources and contacts

Information on screening and treatment of epithelial ovarian cancer, including clinical trials, can be found at:

Auersperg, N. et al. (2001) Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev 22, 255-288Google ScholarPubMed
Cheng, W. et al. (2005) Lineage infidelity of epithelial ovarian cancers is controlled by HOX genes that specify regional identity in the reproductive tract. Nat Med 11, 531-537Google Scholar
Dubeau, L. (1999) The cell of origin of ovarian epithelial tumors and the ovarian surface epithelium dogma: does the emperor have no clothes? Gynecol Oncol 72, 437-442Google Scholar
Crum, C.P. et al. (2007) The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol 19, 3-9CrossRefGoogle ScholarPubMed
http://www.cancer.gov/cancertopics/types/ovarian Google Scholar
http://emice.nci.nih.gov/emice/mouse_models/organ_models/ovarian_modelsGoogle Scholar
Auersperg, N. et al. (2001) Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev 22, 255-288Google ScholarPubMed
Cheng, W. et al. (2005) Lineage infidelity of epithelial ovarian cancers is controlled by HOX genes that specify regional identity in the reproductive tract. Nat Med 11, 531-537Google Scholar
Dubeau, L. (1999) The cell of origin of ovarian epithelial tumors and the ovarian surface epithelium dogma: does the emperor have no clothes? Gynecol Oncol 72, 437-442Google Scholar
Crum, C.P. et al. (2007) The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol 19, 3-9CrossRefGoogle ScholarPubMed
http://www.cancer.gov/cancertopics/types/ovarian Google Scholar
http://emice.nci.nih.gov/emice/mouse_models/organ_models/ovarian_modelsGoogle Scholar