Cancer Causes & Control

, Volume 24, Issue 4, pp 749–757

Agreement for tumor grade of ovarian carcinoma: analysis of archival tissues from the surveillance, epidemiology, and end results residual tissue repository

  • Rayna K. Matsuno
  • Mark E. Sherman
  • Kala Visvanathan
  • Marc T. Goodman
  • Brenda Y. Hernandez
  • Charles F. Lynch
  • Olga B. Ioffe
  • David Horio
  • Charles Platz
  • Sean F. Altekruse
  • Ruth M. Pfeiffer
  • William F. Anderson
Original paper



Emerging data suggest that ovarian cancers differ by tumor grade. However, the reliability of microscopic grade from paraffin tissue in the general medical community and as reflected in population-based cancer registries is unknown.


We examined grade agreement between two gynecologic pathologists and the Surveillance Epidemiology and End Results Residual Tissue Repository (SEER). Grade agreement was assessed with percent observer agreement and kappa coefficients for 664 invasive ovarian carcinomas, using previously defined three-tier and two-tier grading systems. A random subset of ovarian carcinomas was selected to compare intra- and inter-pathologist agreement.


Five hundred and eighty-six of SEER’s 664 tumors were confirmed invasive. Percent agreement was 49 % with fair kappa coefficient = 0.25 (95 % CI: 0.20–0.30) for the 664 tumors. Agreement improved slightly when restricted to the 586 confirmed invasive cancers; it was better for high grade than low grade tumors, for two-tier than three-tier grading systems, and within (66 %) than between study pathologists (43 %). Grade was not a robust independent predictor of ovarian cancer-specific survival.


Grade agreement was fair between SEER and study pathologists irrespective of grading system. Recorded grade in SEER should be used with caution and is probably not a reliable metric for ovarian cancer epidemiology.


Epidemiology Ovarian cancer Tumor grade SEER Kappa coefficient 

Supplementary material

10552_2013_157_MOESM1_ESM.docx (42 kb)
Supplementary material 1 (DOCX 42 kb)


  1. 1.
    Singer G, Kurman RJ, Chang HW, Cho SK, Shih Ie M (2002) Diverse tumorigenic pathways in ovarian serous carcinoma. Am J Pathol 160(4):1223–1228 (Epub 2002/04/12)PubMedCrossRefGoogle Scholar
  2. 2.
    ShihIe M, Kurman RJ (2004) Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol 164(5):1511–1518CrossRefGoogle Scholar
  3. 3.
    Kurman RJ, Shih IM (2008) Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications. Int J Gynecol Pathol 27:151–160PubMedGoogle Scholar
  4. 4.
    Landen CN Jr, Birrer MJ, Sood AK (2008) Early events in the pathogenesis of epithelial ovarian cancer. J Clin Oncol 26(6):995–1005PubMedCrossRefGoogle Scholar
  5. 5.
    Levanon K, Crum C, Drapkin R (2008) New insights into the pathogenesis of serous ovarian cancer and its clinical impact. J Clin Oncol 26(32):5284–5293PubMedCrossRefGoogle Scholar
  6. 6.
    Kuo KT, Guan B, Feng Y, Mao TL, Chen X, Jinawath N et al (2009) Analysis of DNA copy number alterations in ovarian serous tumors identifies new molecular genetic changes in low-grade and high-grade carcinomas. Cancer Res 69(9):4036–4042PubMedCrossRefGoogle Scholar
  7. 7.
    Grimley PM, Matsuno RK, Rosenberg PS, Henson DE, Schwartz AM, Anderson WF (2009) Qualitative age interactions between low and high grade serous ovarian carcinomas. Cancer Epidemiol Biomarkers Prev 18(8):2256–2261PubMedCrossRefGoogle Scholar
  8. 8.
    Classification and staging of malignant tumors in the female pelvis, accepted by the General Assembly of FIGO in New York, April 12, 1970. Acta Obstet Gynecol Scand 50(1):1–7Google Scholar
  9. 9.
    Silverberg SG (2000) Histopathologic grading of ovarian carcinoma: a review and proposal. Int J Gynecol Pathol 19(1):7–15PubMedCrossRefGoogle Scholar
  10. 10.
    Shimizu Y, Kamoi S, Amada S, Akiyama F, Silverberg SG (1998) Toward the development of a universal grading system for ovarian epithelial carcinoma: testing of a proposed system in a series of 461 patients with uniform treatment and follow-up. Cancer 82(5):893–901PubMedCrossRefGoogle Scholar
  11. 11.
    Shimizu Y, Kamoi S, Amada S, Hasumi K, Akiyama F, Silverberg SG (1998) Toward the development of a universal grading system for ovarian epithelial carcinoma. I. Prognostic significance of histopathologic features–problems involved in the architectural grading system. Gynecol Oncol 70(1):2–12PubMedCrossRefGoogle Scholar
  12. 12.
    Malpica A (2008) Grading of ovarian cancer: a histotype-specific approach. Int J Gynecol Pathol 27:175–181PubMedGoogle Scholar
  13. 13.
    Malpica A, Deavers MT, Tornos C, Kurman RJ, Soslow R, Seidman JD et al (2007) Interobserver and intraobserver variability of a two-tier system for grading ovarian serous carcinoma. Am J Surg Pathol 31(8):1168–1174PubMedCrossRefGoogle Scholar
  14. 14.
    Malpica A, Deavers MT, Lu K, Bodurka DC, Atkinson EN, Gershenson DM et al (2004) Grading ovarian serous carcinoma using a two-tier system. Am J Surg Pathol 28(4):496–504PubMedCrossRefGoogle Scholar
  15. 15.
    McCluggage WG (2011) Morphological subtypes of ovarian carcinoma: a review with emphasis on new developments and pathogenesis. Pathology (Phila) 43(5):420–432 (Epub 2011/07/01)CrossRefGoogle Scholar
  16. 16.
    SEER-Surveillance Epidemiology and End Results (2012) [cited 2012 February 06]; Available from:
  17. 17.
    Goodman MT, Hernandez BY, Hewitt S, Lynch CF, Cote TR, Frierson HF Jr et al (2005) Tissues from population-based cancer registries: a novel approach to increasing research potential. Hum Pathol 36(7):812–820PubMedCrossRefGoogle Scholar
  18. 18.
    AJCC (2011) Ovary and primary peritoneal carcinoma. In: Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (eds) AJCC cancer staging manual, 7th edn. Springer, New York, pp 419–428Google Scholar
  19. 19.
    International Classification of Diseases for Oncology 3rd ed (2000) In: Fritz A, Percy C, Jack A, Shanmugaratnam K, Sobin L, Parkin DM, Whelan S (eds) U.S. Interim Version 2000. World Health Organization, GenevaGoogle Scholar
  20. 20.
    Cohen CJ (1960) A coefficient of agreement for nominal scales. Educ Psychol Measur 20:37–46CrossRefGoogle Scholar
  21. 21.
    Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRefGoogle Scholar
  22. 22.
    Peto R, Peto J (1972) Asymptomatically efficient rank invariant test procedures. J Roy Stat Soc A 135((A)):185–198CrossRefGoogle Scholar
  23. 23.
    Gilks CB, Ionescu DN, Kalloger SE, Kobel M, Irving J, Clarke B et al (2008) Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma. Hum Pathol 39(8):1239–1251PubMedCrossRefGoogle Scholar
  24. 24.
    Sugiyama T, Kamura T, Kigawa J, Terakawa N, Kikuchi Y, Kita T et al (2000) Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy. Cancer 88(11):2584–2589 (Epub 2000/06/22)PubMedCrossRefGoogle Scholar
  25. 25.
    Soslow RA (2008) Histologic subtypes of ovarian carcinoma: an overview. Int J Gynecol Pathol 27:161–174PubMedGoogle Scholar
  26. 26.
    Cicchetti DV, Feinstein AR (1990) High agreement but low kappa: II. Resolving the paradoxes. J Clin Epidemiol 43(6):551–558 (Epub 1990/01/01)PubMedCrossRefGoogle Scholar
  27. 27.
    Feinstein AR, Cicchetti DV (1990) High agreement but low kappa: I. The problems of two paradoxes. J Clin Epidemiol 43(6):543–549 (Epub 1990/01/01)PubMedCrossRefGoogle Scholar
  28. 28.
    Last JM (1995) A dictionary of epidemiology, 3rd edn. Oxford University Press, OxfordGoogle Scholar
  29. 29.
    Seidman JD, Yemelyanova A, Cosin JA, Smith A, Kurman RJ (2012) Survival rates for international federation of gynecology and obstetrics stage III ovarian carcinoma by cell type: a study of 262 unselected patients with uniform pathologic review. Int J Gynecol Cancer 22(3):367–371 (Epub 2012/01/13)PubMedCrossRefGoogle Scholar
  30. 30.
    Kobel M, Kalloger SE, Boyd N, McKinney S, Mehl E, Palmer C et al (2008) Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med 5(12):e232PubMedCrossRefGoogle Scholar
  31. 31.
    Leitao MM Jr, Boyd J, Hummer A, Olvera N, Arroyo CD, Venkatraman E et al (2004) Clinicopathologic analysis of early-stage sporadic ovarian carcinoma. Am J Surg Pathol 28(2):147–159PubMedCrossRefGoogle Scholar
  32. 32.
    Singer G, Shih Ie M, Truskinovsky A, Umudum H, Kurman RJ (2003) Mutational analysis of K-ras segregates ovarian serous carcinomas into two types: invasive MPSC (low-grade tumor) and conventional serous carcinoma (high-grade tumor). Int J Gynecol Pathol 22(1):37–41PubMedCrossRefGoogle Scholar
  33. 33.
    Sotiriou C, Pusztai L (2009) Gene-expression signatures in breast cancer. N Engl J Med 360(8):790–800PubMedCrossRefGoogle Scholar
  34. 34.
    Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J et al (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 98(4):262–272PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht (outside the USA) 2013

Authors and Affiliations

  • Rayna K. Matsuno
    • 1
    • 2
    • 3
  • Mark E. Sherman
    • 1
  • Kala Visvanathan
    • 3
  • Marc T. Goodman
    • 2
  • Brenda Y. Hernandez
    • 2
  • Charles F. Lynch
    • 4
  • Olga B. Ioffe
    • 5
  • David Horio
    • 2
  • Charles Platz
    • 6
  • Sean F. Altekruse
    • 7
  • Ruth M. Pfeiffer
    • 1
  • William F. Anderson
    • 1
  1. 1.DHHS/NIH/National Cancer Institute/Division of Cancer Epidemiology and GeneticsRockvilleUSA
  2. 2.Epidemiology DepartmentUniversity of Hawaii Cancer CenterHonoluluUSA
  3. 3.Department of EpidemiologyJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  4. 4.Department of EpidemiologyThe University of IowaIowa CityUSA
  5. 5.Department of PathologyUniversity of Maryland School of MedicineBaltimoreUSA
  6. 6.Department of PathologyUniversity of Iowa Hospitals and ClinicsIowa CityUSA
  7. 7.DHHS/NIH/National Cancer Institute/Division of Cancer Control and Population SciencesRockvilleUSA

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