J Gynecol Oncol.  2013 Jan;24(1):37-43. 10.3802/jgo.2013.24.1.37.

Clear cell histology as a poor prognostic factor for advanced epithelial ovarian cancer: a single institutional case series through central pathologic review

• Miyamoto M
• Takano M
• Goto T
• Kato M
• Sasaki N
• Tsuda H
• Furuya K

• KMID: 2288559
• DOI: http://doi.org/10.3802/jgo.2013.24.1.37

Abstract

OBJECTIVE
Compared with serous adenocarcinoma (SAC), clear cell carcinoma (CCC) often shows chemo-resistance, which would potentially lead to a poor prognosis. On the other hand, there have been arguments over prognoses of CCC and SAC disease. In the present study, multivariate analysis to compare prognosis of CCC patients with that of SAC was aimed for the patients selected from central pathologic review.
METHODS
Between 1984 and 2009, a total of 500 ovarian cancer patients were treated at our university hospital. Among them, 111 patients with CCC and 199 patients with SAC were identified through central pathological review. Overall survival and progression-free survival were compared using Kaplan-Meier method, and prognostic factors were investigated by multiple regression analyses.
RESULTS
Median age was 52 years for CCC and 55 years for SAC (p=0.03). The ratio of stage I patients were significantly higher in CCC compared with SAC (55% vs. 13%, p<0.01). Among evaluable cases, response rate was significantly lower in CCC than that in SAC (32% vs. 78%, p<0.01). No significant differences of progression-free survival and overall survival were observed in stage I patients; however, prognoses of CCC were significantly poorer than those of SAC in advanced-stage disease. In stage II-IV patients, not only residual tumors and clinical stages, but also clear cell histology were identified as predictors for poor prognosis.
CONCLUSION
Clear cell histology was identified as a prognostic factor for advanced-stage ovarian cancers. Histologic subtypes should be considered in further clinical studies, especially for advanced epithelial ovarian cancers.

Keyword

Clear cell adenocarcinoma; Ovarian neoplasm; Serous cystadenocarcinoma; Survival

MeSH Terms

Adenocarcinoma
Adenocarcinoma, Clear Cell
Chlormequat
Cystadenocarcinoma, Serous
Disease-Free Survival
Hand
Humans
Multivariate Analysis
Neoplasm, Residual
Ovarian Neoplasms
Prognosis
Chlormequat

Figure

• 

  Fig. 1 Progression-free and overall survival curves of the patients with advanced-staged disease. (A) Progression-free survival of stage II-IV clear cell carcinoma (CCC, n=51) was significantly worse than that of serous adenocarcinoma (SAC; n=172, p<0.01). (B) Overall survival of stage II-IV CCC (n=51) was significantly better than that of SAC (n=172, p<0.01).

Reference

1. Bray F, Loos AH, Tognazzo S, La Vecchia C. Ovarian cancer in Europe: Cross-sectional trends in incidence and mortality in 28 countries, 1953-2000. Int J Cancer. 2005. 113:977–990.

2. Edwards BK, Brown ML, Wingo PA, Howe HL, Ward E, Ries LA, et al. Annual report to the nation on the status of cancer, 1975-2002, featuring population-based trends in cancer treatment. J Natl Cancer Inst. 2005. 97:1407–1427.

3. Winter WE 3rd, Maxwell GL, Tian C, Carlson JW, Ozols RF, Rose PG, et al. Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007. 25:3621–3627.

4. Chan JK, Tian C, Monk BJ, Herzog T, Kapp DS, Bell J, et al. Prognostic factors for high-risk early-stage epithelial ovarian cancer: a Gynecologic Oncology Group study. Cancer. 2008. 112:2202–2210.

5. Winter WE 3rd, Maxwell GL, Tian C, Sundborg MJ, Rose GS, Rose PG, et al. Tumor residual after surgical cytoreduction in prediction of clinical outcome in stage IV epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2008. 26:83–89.

6. McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996. 334:1–6.

7. Bookman MA, Greer BE, Ozols RF. Optimal therapy of advanced ovarian cancer: carboplatin and paclitaxel vs. cisplatin and paclitaxel (GOG 158) and an update on GOG0 182-ICON5. Int J Gynecol Cancer. 2003. 13:735–740.

8. Serov SF, Scully RE, Sobin LH. Histological typing of ovarian tumors. 1973. Geneva: World Health Organization.

9. Kennedy AW, Biscotti CV, Hart WR, Webster KD. Ovarian clear cell adenocarcinoma. Gynecol Oncol. 1989. 32:342–349.

10. Crozier MA, Copeland LJ, Silva EG, Gershenson DM, Stringer CA. Clear cell carcinoma of the ovary: a study of 59 cases. Gynecol Oncol. 1989. 35:199–203.

11. Omura GA, Brady MF, Homesley HD, Yordan E, Major FJ, Buchsbaum HJ, et al. Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience. J Clin Oncol. 1991. 9:1138–1150.

12. O'Brien ME, Schofield JB, Tan S, Fryatt I, Fisher C, Wiltshaw E. Clear cell epithelial ovarian cancer (mesonephroid): bad prognosis only in early stages. Gynecol Oncol. 1993. 49:250–254.

13. Oncology Committee of Japan Society of Obstetrics and Gynecology. Annual report of the patients with ovarian cancers. Acta Obstet Gynaecol Jpn. 2010. 62:827–910.

14. Yahata T, Banzai C, Tanaka K. Niigata Gynecological Cancer Registry. Histology-specific long-term trends in the incidence of ovarian cancer and borderline tumor in Japanese females: a population-based study from 1983 to 2007 in Niigata. J Obstet Gynaecol Res. 2012. 38:645–650.

15. Sugiyama T, Kamura T, Kigawa J, Terakawa N, Kikuchi Y, Kita T, et al. Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy. Cancer. 2000. 88:2584–2589.

16. Pectasides D, Fountzilas G, Aravantinos G, Kalofonos C, Efstathiou H, Farmakis D, et al. Advanced stage clear-cell epithelial ovarian cancer: the Hellenic Cooperative Oncology Group experience. Gynecol Oncol. 2006. 102:285–291.

17. 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? [abstract]. Proc Am Soc Clin Oncol. 2003. 22:1797.

18. Ho CM, Huang YJ, Chen TC, Huang SH, Liu FS, Chang Chien CC, et al. Pure-type clear cell carcinoma of the ovary as a distinct histological type and improved survival in patients treated with paclitaxel-platinum-based chemotherapy in pure-type advanced disease. Gynecol Oncol. 2004. 94:197–203.

19. Utsunomiya H, Akahira J, Tanno S, Moriya T, Toyoshima M, Niikura H, et al. Paclitaxel-platinum combination chemotherapy for advanced or recurrent ovarian clear cell adenocarcinoma: a multicenter trial. Int J Gynecol Cancer. 2006. 16:52–56.

20. Ho CM, Chien TY, Shih BY, Huang SH. 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. 88:394–399.

21. 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. 19:88–93.

22. Anglesio MS, Carey MS, Kobel M, Mackay H, Huntsman DG. Vancouver Ovarian Clear Cell Symposium Speakers. Clear cell carcinoma of the ovary: a report from the first Ovarian Clear Cell Symposium, June 24th, 2010. Gynecol Oncol. 2011. 121:407–415.

23. Takano M, Sugiyama T, Yaegashi N, Suzuki M, Tsuda H, Sagae S, et al. The impact of complete surgical staging upon survival in early-stage ovarian clear cell carcinoma: a multi-institutional retrospective study. Int J Gynecol Cancer. 2009. 19:1353–1357.

24. Takano M, Kikuchi Y, Yaegashi N, Kuzuya K, Ueki M, Tsuda H, et al. Clear cell carcinoma of the ovary: a retrospective multicentre experience of 254 patients with complete surgical staging. Br J Cancer. 2006. 94:1369–1374.

25. Bamias A, Psaltopoulou T, Sotiropoulou M, Haidopoulos D, Lianos E, Bournakis E, et al. Mucinous but not clear cell histology is associated with inferior survival in patients with advanced stage ovarian carcinoma treated with platinum-paclitaxel chemotherapy. Cancer. 2010. 116:1462–1468.

26. Han G, Gilks CB, Leung S, Ewanowich CA, Irving JA, Longacre TA, et al. Mixed ovarian epithelial carcinomas with clear cell and serous components are variants of high-grade serous carcinoma: an interobserver correlative and immunohistochemical study of 32 cases. Am J Surg Pathol. 2008. 32:955–964.

27. Kajiyama H, Shibata K, Mizuno M, Yamamoto E, Fujiwara S, Umezu T, et al. Postrecurrent oncologic outcome of patients with ovarian clear cell carcinoma. Int J Gynecol Cancer. 2012. 22:801–806.

28. Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simonsen E, et al. Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst. 2000. 92:699–708.

29. 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. 21:3194–3200.

30. Takakura S, Takano M, Takahashi F, Saito T, Aoki D, Inaba N, et al. Randomized phase II trial of paclitaxel plus carboplatin therapy versus irinotecan plus cisplatin therapy as first-line chemotherapy for clear cell adenocarcinoma of the ovary: a JGOG study. Int J Gynecol Cancer. 2010. 20:240–247.

31. Gynecologic Cancer Intergroup. Japanese Gynecologic Oncology Group. Ovarian trial protocol version 3.1 (GCIG/JGOG3017) [Internet]. c2009. cited 2012 Dec 10. Tokyo: Japanese Gynecologic Oncology Group;Available from: http://www.gcig.igcs.org/files/JGOG3017_Protocol.pdf#search='JGOG 3017'.