Skip to main content
SpringerLink
Log in

Ovarian Clear Cell Carcinoma

  • Chapter
  • First Online:
Rare and Uncommon Gynecological Cancers

  • 877 Accesses

Abstract

Clear cell carcinoma is a distinct entity from other epithelial ovarian carcinomas, not simply because of its characteristic histology, but because of its specific biological and clinical behaviour. It is the second most common histological subtype of ovarian cancer, after serous carcinoma, accounting for 4–12% of ovarian epithelial cancers in Western countries [1, 2]. It comprises a greater proportion of ovarian epithelial cancers in Japan, up to 20% [1], where the incidence is rising [3]. Even in the West, clear cell carcinoma accounts for a significantly higher proportion of ovarian cancers in people of Japanese descent, compared to all other ethnic groups [2].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Itamochi H, Kigawa J, Terakawa N. Mechanisms of chemoresistance and poor prognosis in ovarian clear cell carcinoma. Cancer Sci. 2008;99(4):653–8.

    Article  CAS  PubMed  Google Scholar 

  2. Chan JK, Teoh D, Hu JM, Shin JY, Osann K, Kapp DS. Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? A study of 1411 clear cell ovarian cancers. Gynecol Oncol. 2008;109(3):370–6.

    Article  PubMed  Google Scholar 

  3. Ushijimi K. Current status of gynecologic cancer in Japan. J Gynecol Oncol. 2009;20(2):67–71.

    Article  Google Scholar 

  4. Lim MC, Lee DO, Kang S, Seo SS, Lee BY, Park SY. Clinical manifestations in patients with ovarian clear cell carcinoma with or without co-existing endometriosis. Gynecol Endocrinol. 2009;25(7):435–40.

    Article  PubMed  Google Scholar 

  5. Nagle CM, Olsen CM, Webb PM, Jordan SJ, Whiteman DC, Green AC, et al. Endometrioid and clear cell ovarian cancers: a comparative analysis of risk factors. Eur J Cancer. 2008;44(16):2477–84.

    Article  PubMed  Google Scholar 

  6. Olsen CM, Nagle CM, Whiteman DC, Purdie DM, Green AC, Webb PM, et al. Body size and risk of epithelial ovarian and related cancers: a population-based case-control study. Int J Cancer. 2008;123(2):450–6.

    Article  CAS  PubMed  Google Scholar 

  7. Ness RB, Cramer DW, Goodman MT, Kjaer SK, Mallin K, Mosgaard BJ, et al. Infertility, fertility drugs, and ovarian cancer: a pooled analysis of case-control studies. Am J Epidemiol. 2002;155(3):217–24.

    Article  PubMed  Google Scholar 

  8. Kobayashi H, Sumimoto K, Kitanaka T, Yamada Y, Sado T, Sakata M, et al. Ovarian endometrioma–risks factors of ovarian cancer development. Eur J Obstet Gynecol Reprod Biol. 2008;138(2):187–93.

    Article  PubMed  Google Scholar 

  9. Orezzoli JP, Russell AH, Oliva E, Del Carmen MG, Eichhorn J, Fuller AF. Prognostic implication of endometriosis in clear cell carcinoma of the ovary. Gynecol Oncol. 2008;110(3):336–44.

    Article  CAS  PubMed  Google Scholar 

  10. Yamamoto S, Tsuda H, Takano M, Hase K, Tamai S, Matsubara O. Clear-cell adenofibroma can be a clonal precursor for clear-cell adenocarcinoma of the ovary: a possible alternative ovarian clear-cell carcinogenic pathway. J Pathol. 2008;216(1):103–10.

    CAS  PubMed  Google Scholar 

  11. Veras EMD, Mao T-LMDP, Ayhan AMDP, Ueda SMD, Lai HPM, Hayran MMD, et al. Cystic and adenofibromatous clear cell carcinomas of the ovary: distinctive tumors that differ in their pathogenesis and behavior: a clinicopathologic analysis of 122 cases. Am J Surg Pathol. 2009;33(6):844–53.

    Article  PubMed  Google Scholar 

  12. Yamamoto S, Tsuda H, Yoshikawa T, Kudoh K, Kita T, Furuya K, et al. Clear cell adenocarcinoma associated with clear cell adenofibromatous components: a subgroup of ovarian clear cell adenocarcinoma with distinct clinicopathologic characteristics. Am J Surg Pathol. 2007;31(7):999–1006.

    Article  PubMed  Google Scholar 

  13. Roth LM, Langley FA, Fox H, Wheeler JE, Czernobilsky B. Ovarian clear cell adenofibromatous tumors. Benign, of low malignant potential, and associated with invasive clear cell carcinoma. Cancer. 1984;53(5):1156–63.

    Article  CAS  PubMed  Google Scholar 

  14. Savvari P, Peitsidis P, Alevizaki M, Dimopoulos MA, Antsaklis A, Papadimitriou CA. Paraneoplastic humorally mediated hypercalcemia induced by parathyroid hormone-related protein in gynecologic malignancies: a systematic review. Onkologie. 2009;32(8–9):517–23.

    Article  PubMed  Google Scholar 

  15. Duska LR, Garrett L, Henretta M, Ferriss JS, Lee L, Horowitz N. When ‘never-events’ occur despite adherence to clinical guidelines: The case of venous thromboembolism in clear cell cancer of the ovary compared with other epithelial histologic subtypes. Gynecol Oncol. 2010;116(3):374–7.

    Article  PubMed  Google Scholar 

  16. Lim MC, Lee HS, Kang S, Seo SS, Lee BY, Park SY. Minimizing tumor burden by extensive cytoreductive surgery decreases postoperative venous thromboembolism in ovarian clear cell carcinoma. Arch Gynecol Obstet. 2010;281(2):329–34.

    Article  PubMed  Google Scholar 

  17. Uno K, Homma S, Satoh T, Nakanishi K, Abe D, Matsumoto K, et al. Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer. Br J Cancer. 2007;96(2):290–5.

    Article  CAS  PubMed  Google Scholar 

  18. Ho C-M, Chien T-Y, Shih B-Y, Huang S-H. Evaluation of complete surgical staging with pelvic and para-aortic lymphadenectomy and paclitaxel plus carboplatin chemotherapy for improvement of survival in stage I ovarian clear cell carcinoma. Gynecol Oncol. 2003;88(3):394–9.

    Article  CAS  PubMed  Google Scholar 

  19. Chan JK, Munro EG, Cheung MK, Husain A, Teng NN, Berek JS, et al. Association of lymphadenectomy and survival in stage I ovarian cancer patients. Obstet Gynecol. 2007;109(1):12–9.

    PubMed  Google Scholar 

  20. Suzuki S, Kajiyama H, Shibata K, Ino K, Nawa A, Sakakibara K, et al. Is there any association between retroperitoneal lymphadenectomy and survival benefit in ovarian clear cell carcinoma patients? Ann Oncol. 2008;19(7):1284–7.

    Article  CAS  PubMed  Google Scholar 

  21. Kajiyama H, Shibata K, Suzuki S, Ino K, Yamamoto E, Mizuno K, et al. Is there any possibility of fertility-sparing surgery in patients with clear-cell carcinoma of the ovary? Gynecol Oncol. 2008;111(3):523–6.

    Article  PubMed  Google Scholar 

  22. Timmers PJ, Zwinderman AH, Teodorovic I, Vergote I, Trimbos JB. Clear cell carcinoma compared to serous carcinoma in early ovarian cancer: same prognosis in a large randomized trial. Int J Gynecol Cancer. 2009;19(1):88–93.

    CAS  PubMed  Google Scholar 

  23. du Bois A, Luck H-J, Meier W, Adams H-P, Mobus V, Costa S, et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst. 2003;95(17):1320–9.

    PubMed  Google Scholar 

  24. Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage iii ovarian cancer: a gynecologic oncology group study. J Clin Oncol. 2003;21(17):3194–200.

    Article  CAS  PubMed  Google Scholar 

  25. Enomoto T, Kuragaki C, Yamasaki M, Sugita N, Otsuki Y, Ikegami H, et al. Is clear cell carcinoma and mucinous carcinoma of the ovary sensitive to combination chemotherapy with paclitaxel and carboplatin? Proc Am Soc Clin Oncol. 2003;22:abstr 1797.

    Google Scholar 

  26. Takano M, Kita T, Kikuchi Y, Yaegashi N, Kuzuya K, Tsuda H, et al. Clinical characteristics of clear cell adenocarcinoma of the ovary -Japan Clear Cell Carcinoma Study Group. J Clin Oncol (Meeting Abstracts). 2005;23(16 Suppl):5123.

    Google Scholar 

  27. Sugiyama T, Yakushiji M, Kamura T, Ikeda M, Umesaki N, Hasegawa K, et al. Irinotecan (CPT-11) and cisplatin as first-line chemotherapy for advanced ovarian cancer. Oncology. 2002;63(1):16–22.

    Article  CAS  PubMed  Google Scholar 

  28. Takano M, Kikuchi Y, Yaegashi N, Suzuki M, Tsuda H, Sagae S, et al. Adjuvant chemotherapy with irinotecan hydrochloride and cisplatin for clear cell carcinoma of the ovary. Oncol Rep. 2006;16(6):1301–6.

    CAS  PubMed  Google Scholar 

  29. Takano M, Sugiyama T, Yaegashi N, Suzuki M, Tsuda H, Sagae S, et al. Progression-free survival and overall survival of patients with clear cell carcinoma of the ovary treated with paclitaxel-carboplatin or irinotecan-cisplatin: retrospective analysis. Int J Clin Oncol. 2007;12(4):256–60.

    Article  CAS  PubMed  Google Scholar 

  30. http://www.gcig.igcs.org/files/JGOG3017_Protocol.pdf. Accessed 3 september 2010.

  31. Takano M, Sugiyama T, Yaegashi N, Sakuma M, Suzuki M, Saga Y, et al. Low response rate of second-line chemotherapy for recurrent or refractory clear cell carcinoma of the ovary: a retrospective Japan Clear Cell Carcinoma Study. Int J Gynecol Cancer. 2008;18(5):937–42.

    Article  CAS  PubMed  Google Scholar 

  32. Crotzer DR, Sun CC, Coleman RL, Wolf JK, Levenback CF, Gershenson DM. Lack of effective systemic therapy for recurrent clear cell carcinoma of the ovary. Gynecol Oncol. 2007;105(2):404–8.

    Article  PubMed  Google Scholar 

  33. Pectasides D, Fountzilas G, Aravantinos G, et al. Advanced stage clear-cell epithelial ovarian cancer: the Hellenic cooperative oncology group experience. Gynecol Oncol. 2006;102(2):285–91.

    Article  PubMed  Google Scholar 

  34. Geyer JT, Lopez-Garcia M, Sanches-Estevez C, Sarrio D, Moreno-Bueno G, Franceschetti I, et al. Pathogenic pathways in ovarian endometrioid adenocarcinoma. A molecular study of 29 cases. Am J Surg Pathol. 2009;33(8):1157–63.

    Article  PubMed  Google Scholar 

  35. Shih I-M, Kurman RJ. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol. 2004; 164(5):1511-8

    Google Scholar 

  36. Young RH, Scully RE. Oxyphilic clear cell carcinoma of the ovary. A report of nine cases. Am J Surg Pathol. 1987;11(9):661–7.

    Article  CAS  PubMed  Google Scholar 

  37. Skirnisdottir I, Seidal T, Karlsson MG, Sorbe B. Clinical and biological characteristics of clear cell carcinomas of the ovary in FIGO stages I-II. Int J Oncol. 2005;26(1):177–83.

    PubMed  Google Scholar 

  38. Iwamoto H, Fukasawa H, Honda T, Hirata S, Hoshi K. HER-2/neu expression in ovarian clear cell carcinomas. Int J Gynecol Cancer. 2003;13(1):28–31.

    Article  CAS  PubMed  Google Scholar 

  39. Shimizu M, Nikaido T, Toki T, Shiozawa T, Fujii S. Clear cell carcinoma has an expression pattern of cell cycle regulatory molecules that is unique among ovarian adenocarcinomas. Cancer. 1999;85(3):669–77.

    Article  CAS  PubMed  Google Scholar 

  40. Kato N, Sasou S, Motoyama T. Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary. Mod Pathol. 2006;19(1):83–9.

    Article  CAS  PubMed  Google Scholar 

  41. Maeda D, Ota S, Takazawa Y, Aburatani H, Nakagawa S, Yano T, et al. Glypican-3 expression in clear cell adenocarcinoma of the ovary. Mod Pathol. 2009; 22(6):824-32.

    Article  PubMed  Google Scholar 

  42. Hashiguchi Y, Tsuda H, Inoue T, Berkowitz RS, Mok SC. PTEN expression in clear cell adenocarcinoma of the ovary. Gynecol Oncol. 2006;101(1):71–5.

    Article  CAS  PubMed  Google Scholar 

  43. Sato N, Tsunoda H, Nishida M, et al. 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 carcinoma and clear cell carcinoma of the ovary. Cancer Res. 2000;60(24):7052–6.

    CAS  PubMed  Google Scholar 

  44. Kaneuchi M, Sasaki M, Tanaka Y, et al. WT1 and WT1-AS genes are inactivated by promoter methylation in ovarian clear cell adenocarcinoma. Cancer. 2005;104(9):1924–30.

    Article  CAS  PubMed  Google Scholar 

  45. Holcomb K, Delatorre R, Pedemonte B, McLeod C, Anderson L, Chambers J. E-cadherin expression in endometrioid, papillary serous, and clear cell carcinoma of the endometrium. Obstet Gynecol. 2002;100(6):1290–5.

    Article  CAS  PubMed  Google Scholar 

  46. Suehiro Y, Sakamoto M, Umayahara K, et al. Genetic aberrations detected by comparative genomic hybridization in ovarian clear cell adenocarcinomas. Oncology. 2000;59(1):50–6.

    Article  CAS  PubMed  Google Scholar 

  47. Dent J, Hall GD, Wilkinson N, et al. Cytogenetic alterations in ovarian clear cell carcinoma detected by comparative genomic hybridisation. Br J Cancer. 2003;88(10):1578–83.

    Article  CAS  PubMed  Google Scholar 

  48. Cairns P, Tokino K, Eby Y, Sidransky D. Localization of tumor suppressor loci on chromosome 9 in primary human renal cell carcinomas. Cancer Res. 1995;55(2):224–7.

    CAS  PubMed  Google Scholar 

  49. Köbel M, Kalloger SE, Carrick J, Huntsman D, Asad H, Oliva E, et al. A limited panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of the ovary. Am J Surg Pathol. 2009; 33(1):14-21

    Google Scholar 

  50. Saga Y, Ohwada M, Suzuki M, Konno R, Kigawa J, Ueno S, et al. Glutathione peroxidase 3 is a candidate mechanism of anticancer drug resistance of ovarian clear cell adenocarcinoma. Oncol Rep. 2008;20(6):1299–303.

    CAS  PubMed  Google Scholar 

  51. Umezu T, Shibata K, Shimaoka M, Kajiyama H, Yamamoto E, Ino K, et al. Gene silencing of glypican-3 in clear cell carcinoma of the ovary renders it more sensitive to the apoptotic agent paclitaxel in vitro and in vivo. Cancer Sci. 2010;101(1):143–8.

    Article  CAS  PubMed  Google Scholar 

  52. Lee S, Garner EI, Welch WR, Berkowitz RS, Mok SC. Over-expression of hypoxia-inducible factor 1 alpha in ovarian clear cell carcinoma. Gynecol Oncol. 2007;106(2):311–7.

    Article  CAS  PubMed  Google Scholar 

  53. Kim A, Enomoto T, Serada S, Ueda Y, Takahashi T, Ripley B, et al. Enhanced expression of Annexin A4 in clear cell carcinoma of the ovary and its association with chemoresistance to carboplatin. Int J Cancer. 2009;125(10):2316–22.

    Article  CAS  PubMed  Google Scholar 

  54. Ferrandina G, Mey V, Nannizzi S, Ricciardi S, Petrillo M, Ferlini C, et al. Expression of nucleoside transporters, deoxycitidine kinase, ribonucleotide reductase regulatory subunits, and gemcitabine catabolic enzymes in primary ovarian cancer. Cancer Chemother Pharmacol. 2010;65(4):679–86.

    Article  CAS  PubMed  Google Scholar 

  55. Zorn KK, Bonome T, Gangi L, Chandramouli GV, Awtrey CS, Gardner GJ, et al. Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer. Clin Cancer Res. 2005; 11(18):6422-30

    Google Scholar 

  56. Tsuchiya A, Sakamoto M, Yasuda J, et al. Expression profiling in ovarian clear cell carcinoma: identification of hepatocyte nuclear factor-1 beta as a molecular marker and a possible molecular target for therapy of ovarian clear cell carcinoma. Am J Pathol. 2003;163(6):2503–12.

    CAS  PubMed  Google Scholar 

  57. Gütgemann I, Lehman NL, Jackson PK, Longacre TA. Emi1 protein accumulation implicates misregulation of the anaphase promoting complex/cyclosome pathway in ovarian clear cell carcinoma. Mod Pathol. 2008; 21(4):445-54.

    Google Scholar 

  58. Kato N, Motoyama T. Overexpression of osteopontin in clear cell carcinoma of the ovary: close association with HNF-1beta expression. Histopathology. 2008;52(6):682–8.

    Article  CAS  PubMed  Google Scholar 

  59. Ho CM, Lin MC, Huang SH, Huang CJ, Lai HC, Chien TY, et al. PTEN promoter methylation and LOH of 10q22-23 locus in PTEN expression of ovarian clear cell adenocarcinomas. Gynecol Oncol. 2009;112(2):307–13.

    Article  CAS  PubMed  Google Scholar 

  60. Furnari FB, Huang HJ, Cavenee WK. The phosphoinositol phosphatase activity of PTEN mediates a serum-sensitive G1 growth arrest in glioma cells. Cancer Res. 1998;58(22):5002–8.

    CAS  PubMed  Google Scholar 

  61. Okuda T, Otsuka J, Sekizawa A, et al. p53 mutations and overexpression affect prognosis of ovarian endometrioid cancer but not clear cell cancer. Gynecol Oncol. 2003;88(3):318–25.

    Article  CAS  PubMed  Google Scholar 

  62. Hua K, Feng W, Cao Q, Zhou X, Lu X, Feng Y. Estrogen and progestin regulate metastasis through the PI3K/AKT pathway in human ovarian cancer. Int J Oncol. 2008;33(5):959–67.

    CAS  PubMed  Google Scholar 

  63. Mabuchi S, Kawase C, Altomare DA, Morishige K, Sawada K, Hayashi M. et al. mTOR is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary. Clin Cancer Res. 2009; 15(17):5404-13.

    Article  CAS  PubMed  Google Scholar 

  64. Tan DS, Kaye S. Ovarian clear cell adenocarcinoma: a continuing enigma. J Clin Pathol. 2007; 60(4):355-60.

    Google Scholar 

  65. Kuo KT, Mao TL, Jones S, Veras E, Ayhan A, Wang TL, et al. Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma. Am J Pathol. 2009;174(5):1597–601.

    Article  CAS  PubMed  Google Scholar 

  66. Yoshida S, Furukawa N, Haruta S, Tanase Y, Kanayama S, Noguchi T, et al. Theoretical model of treatment strategies for clear cell carcinoma of the ovary: focus on perspectives. Cancer Treat Rev. 2009;35(7):608–15.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clatterbridge Centre for Oncology, Merseyside, UK

    Amy Ford

  2. School of Cancer Studies, University of Liverpool, Liverpool, L69 3BX, UK

    John A. Green

Authors
  1. Amy Ford
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John A. Green
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amy Ford .

Editor information

Editors and Affiliations

  1. Beatson Oncology Centre, Gartnavel General Hospital, Great Western Road 1053, Glasgow, G12 0YN, United Kingdom

    Nicholas Reed

  2. Clatterbridge Centre for Oncology, University of Liverpool, Clatterbridge Road, Wirral, Merseyside, L63 4JY, United Kingdom

    John Alan Green

  3. MD Anderson Cancer Center, Dept. Gynecologic Oncology, University of Texas, Holcombe Blvd . 1515, Houston, 77030, Texas, USA

    David M. Gershenson

  4. Stobhill Hospital, North Glasgow University Hospitals NHS T, Baornock Road 133, Glasgow, G61 1Ql, United Kingdom

    Nadeem Siddiqui

  5. , Department of Radiology, Victoria Infirmary, Langside Road, Glasgow, G42 9TY, United Kingdom

    Rachel Connor

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Berlin Heidelberg

About this chapter

Cite this chapter

Ford, A., Green, J.A. (2011). Ovarian Clear Cell Carcinoma. In: Reed, N., Green, J., Gershenson, D., Siddiqui, N., Connor, R. (eds) Rare and Uncommon Gynecological Cancers. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-13492-0_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-13492-0_7

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-13491-3

  • Online ISBN: 978-3-642-13492-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation