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Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1996 Feb;49(2):142–148. doi: 10.1136/jcp.49.2.142

Value of quantitative pathological variables as prognostic factors in advanced ovarian carcinoma.

M Brinkhuis 1, J P Baak 1, G A Meijer 1, P J van Diest 1, O Mogensen 1, P Bichel 1, J P Neijt 1
PMCID: PMC500348  PMID: 8655681

Abstract

AIMS: To evaluate correlations among clinical, pathological, morphometric, stereological, and DNA flow cytometric variables and their prognostic value in advanced ovarian cancer. METHODS: Tissue was collected from 180 patients with advanced ovarian cancer. All 180 had undergone debulking surgery and were being treated with cisplatin. Long term follow up was available for all patients. The mitotic activity index (MAI), volume % of epithelium (VPE), mean nuclear area (MNA), standard deviation of the nuclear area (SDNA), estimates of volume weighted mean nuclear volume (nu v), and variables obtained from minimum spanning tree (MST) analysis were assessed in the least differentiated tumour section in each case. DNA flow cytometry was also performed. RESULTS: Quantitative pathological features differed significantly with respect to histological grade. The MAI, MNA, SDNA, and the number of points connected to three neighbours differed significantly among the different DNA ploidy groups. The VPE and number of points connected to two or three neighbours differed significantly between FIGO stages III and IV. Fifty two (29%) patients survived. FIGO stage, residual disease and SDNA had prognostic significance on both univariate and multivariate survival analysis. In patients with FIGO III stage disease and residual tumour nodes < or = 2 cm in diameter (67 patients, 29 (43%) survivors) a prognostic index was established based on SDNA and of the line length of the MST. The median survival time was not reached in a subgroup of patients with favourable prognosis (overall survival 57%). Median survival was 32 months for patients with an unfavourable index score (overall survival 28%). CONCLUSION: Morphometric variables have important additional value in predicting prognosis in patients with advanced ovarian cancer.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baak J. P., Ladekarl M., Sørensen F. B. Reproducibility of mean nuclear volume and correlation with mean nuclear area in breast cancer: an investigation of various sampling schemes. Hum Pathol. 1994 Jan;25(1):80–85. doi: 10.1016/0046-8177(94)90175-9. [DOI] [PubMed] [Google Scholar]
  2. Baak J. P., Langley F. A., Talerman A., Delemarre J. F. The prognostic variability of ovarian tumor grading by different pathologists. Gynecol Oncol. 1987 Jun;27(2):166–172. doi: 10.1016/0090-8258(87)90289-7. [DOI] [PubMed] [Google Scholar]
  3. Baak J. P., Schipper N. W., Wisse-Brekelmans E. C., Ceelen T., Bosman F. T., van Geuns H., Wils J. The prognostic value of morphometrical features and cellular DNA content in cis-platin treated late ovarian cancer patients. Br J Cancer. 1988 May;57(5):503–508. doi: 10.1038/bjc.1988.114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baak J. P., van Diest P. J., Ariens A. T., van Beek M. W., Bellot S. M., Fijnheer J., van Gorp L. H., Kwee W. S., Los J., Peterse H. C. The Multicenter Morphometric Mammary Carcinoma Project (MMMCP). A nationwide prospective study on reproducibility and prognostic power of routine quantitative assessments in The Netherlands. Pathol Res Pract. 1989 Nov;185(5):664–670. doi: 10.1016/S0344-0338(89)80213-4. [DOI] [PubMed] [Google Scholar]
  5. Bichel P., Jakobsen A. A new histologic grading index in ovarian carcinoma. Int J Gynecol Pathol. 1989;8(2):147–155. doi: 10.1097/00004347-198906000-00008. [DOI] [PubMed] [Google Scholar]
  6. Fleege J. C., van Diest P. J., Baak J. P. Systematic random sampling for selective interactive nuclear morphometry in breast cancer sections. Refinement and multiobserver evaluation. Anal Quant Cytol Histol. 1993 Aug;15(4):281–289. [PubMed] [Google Scholar]
  7. Folkman J., Watson K., Ingber D., Hanahan D. Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature. 1989 May 4;339(6219):58–61. doi: 10.1038/339058a0. [DOI] [PubMed] [Google Scholar]
  8. Friedlander M. L., Hedley D. W., Swanson C., Russell P. Prediction of long-term survival by flow cytometric analysis of cellular DNA content in patients with advanced ovarian cancer. J Clin Oncol. 1988 Feb;6(2):282–290. doi: 10.1200/JCO.1988.6.2.282. [DOI] [PubMed] [Google Scholar]
  9. Frost P., Levin B. Clinical implications of metastatic process. Lancet. 1992 Jun 13;339(8807):1458–1461. doi: 10.1016/0140-6736(92)92040-m. [DOI] [PubMed] [Google Scholar]
  10. Gundersen H. J., Bagger P., Bendtsen T. F., Evans S. M., Korbo L., Marcussen N., Møller A., Nielsen K., Nyengaard J. R., Pakkenberg B. The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. APMIS. 1988 Oct;96(10):857–881. doi: 10.1111/j.1699-0463.1988.tb00954.x. [DOI] [PubMed] [Google Scholar]
  11. Gundersen H. J., Bendtsen T. F., Korbo L., Marcussen N., Møller A., Nielsen K., Nyengaard J. R., Pakkenberg B., Sørensen F. B., Vesterby A. Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS. 1988 May;96(5):379–394. doi: 10.1111/j.1699-0463.1988.tb05320.x. [DOI] [PubMed] [Google Scholar]
  12. Gundersen H. J., Jensen E. B. Stereological estimation of the volume-weighted mean volume of arbitrary particles observed on random sections. J Microsc. 1985 May;138(Pt 2):127–142. doi: 10.1111/j.1365-2818.1985.tb02607.x. [DOI] [PubMed] [Google Scholar]
  13. Haapasalo H., Collan Y., Atkin N. B., Pesonen E., Seppä A. Prognosis of ovarian carcinomas: prediction by histoquantitative methods. Histopathology. 1989 Aug;15(2):167–178. doi: 10.1111/j.1365-2559.1989.tb03064.x. [DOI] [PubMed] [Google Scholar]
  14. Hart I. R., Saini A. Biology of tumour metastasis. Lancet. 1992 Jun 13;339(8807):1453–1457. doi: 10.1016/0140-6736(92)92039-i. [DOI] [PubMed] [Google Scholar]
  15. Högberg T., Wang G., Risberg B., Guerrieri C., Hittson J., Boeryd B., K>>gedal B., Simonsen E. Nuclear morphometry: a strong prognostic factor for survival after secondary surgery in advanced ovarian cancer. Int J Gynecol Cancer. 1992 Jul;2(4):198–206. doi: 10.1046/j.1525-1438.1992.02040198.x. [DOI] [PubMed] [Google Scholar]
  16. Jakobsen A., Bichel P. Ploidy level, histopathological differentiation and response to chemotherapy in serious ovarian cancer. Eur J Cancer Clin Oncol. 1989 Nov;25(11):1589–1593. doi: 10.1016/0277-5379(89)90302-7. [DOI] [PubMed] [Google Scholar]
  17. Kaern J., Tropé C. G., Kristensen G. B., Pettersen E. O. Flow cytometric DNA ploidy and S-phase heterogeneity in advanced ovarian carcinoma. Cancer. 1994 Apr 1;73(7):1870–1877. doi: 10.1002/1097-0142(19940401)73:7<1870::aid-cncr2820730716>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  18. Kallioniemi O. P. Comparison of fresh and paraffin-embedded tissue as starting material for DNA flow cytometry and evaluation of intratumor heterogeneity. Cytometry. 1988 Mar;9(2):164–169. doi: 10.1002/cyto.990090211. [DOI] [PubMed] [Google Scholar]
  19. Kjaer S. K., Storm H. H. Survival of Danish cancer patients 1943-1987. Female genital organs. APMIS Suppl. 1993;33:107–121. [PubMed] [Google Scholar]
  20. Ludescher C., Weger A. R., Lindholm J., Oefner D., Hausmaninger H., Reitsamer R., Mikuz G. Prognostic significance of tumor cell morphometry, histopathology, and clinical parameters in advanced ovarian carcinoma. Int J Gynecol Pathol. 1990;9(4):343–351. doi: 10.1097/00004347-199010000-00006. [DOI] [PubMed] [Google Scholar]
  21. Lund B., Williamson P., van Houwelingen H. C., Neijt J. P. Comparison of the predictive power of different prognostic indices for overall survival in patients with advanced ovarian carcinoma. Cancer Res. 1990 Aug 1;50(15):4626–4629. [PubMed] [Google Scholar]
  22. Mogensen O., Sørensen F.B., Bichel P., Jakobsen A. Nuclear volume and prognosis in ovarian cancer. Int J Gynecol Cancer. 1992 May;2(3):141–146. doi: 10.1046/j.1525-1438.1992.02030141.x. [DOI] [PubMed] [Google Scholar]
  23. Neijt J. P., ten Bokkel Huinink W. W., van der Burg M. E., van Oosterom A. T., Vriesendorp R., Kooyman C. D., van Lindert A. C., Hamerlynck J. V., van Lent M., van Houwelingen J. C. Randomised trial comparing two combination chemotherapy regimens (Hexa-CAF vs CHAP-5) in advanced ovarian carcinoma. Lancet. 1984 Sep 15;2(8403):594–600. doi: 10.1016/s0140-6736(84)90594-4. [DOI] [PubMed] [Google Scholar]
  24. Neijt J. P., ten Bokkel Huinink W. W., van der Burg M. E., van Oosterom A. T., Willemse P. H., Vermorken J. B., van Lindert A. C., Heintz A. P., Aartsen E., van Lent M. Long-term survival in ovarian cancer. Mature data from The Netherlands Joint Study Group for Ovarian Cancer. Eur J Cancer. 1991;27(11):1367–1372. doi: 10.1016/0277-5379(91)90011-2. [DOI] [PubMed] [Google Scholar]
  25. Petersen S. E. Setting up and running a microscope-based flow cytometer. Cytometry. 1983 Jan;3(4):305–307. doi: 10.1002/cyto.990030414. [DOI] [PubMed] [Google Scholar]
  26. Piver M. S. Ovarian carcinoma. A decade of progress. Cancer. 1984 Dec 1;54(11 Suppl):2706–2715. doi: 10.1002/1097-0142(19841201)54:2+<2706::aid-cncr2820541417>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  27. Richardson G. S., Scully R. E., Nikrui N., Nelson J. H., Jr Common epithelial cancer of the ovary (2). N Engl J Med. 1985 Feb 14;312(7):415–424. doi: 10.1056/NEJM198502143120706. [DOI] [PubMed] [Google Scholar]
  28. Rodenburg C. J., Cornelisse C. J., Hermans J., Fleuren G. J. DNA flow cytometry and morphometry as prognostic indicators in advanced ovarian cancer: a step forward in predicting the clinical outcome. Gynecol Oncol. 1988 Feb;29(2):176–187. doi: 10.1016/0090-8258(88)90212-0. [DOI] [PubMed] [Google Scholar]
  29. Rodenburg C. J., Ploem-Zaaijer J. J., Cornelisse C. J., Mesker W. E., Hermans J., Heintz P. A., Ploem J. S., Fleuren G. J. Use of DNA image cytometry in addition to flow cytometry for the study of patients with advanced ovarian cancer. Cancer Res. 1987 Aug 1;47(15):3938–3941. [PubMed] [Google Scholar]
  30. Smith E. M., Anderson B. The effects of symptoms and delay in seeking diagnosis on stage of disease at diagnosis among women with cancers of the ovary. Cancer. 1985 Dec 1;56(11):2727–2732. doi: 10.1002/1097-0142(19851201)56:11<2727::aid-cncr2820561138>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  31. Sørensen F. B. Stereological estimation of the mean and variance of nuclear volume from vertical sections. J Microsc. 1991 May;162(Pt 2):203–229. doi: 10.1111/j.1365-2818.1991.tb03132.x. [DOI] [PubMed] [Google Scholar]
  32. Takahashi Y., Takenaka A., Ishiguro T., Noda Y. Intratumoral DNA heterogeneity correlated with lymph node involvement and surgical staging in epithelial ovarian cancer by flow cytometry. Cancer. 1994 Jun 15;73(12):3011–3014. doi: 10.1002/1097-0142(19940615)73:12<3011::aid-cncr2820731219>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  33. Tannock I. Cell kinetics and chemotherapy: a critical review. Cancer Treat Rep. 1978 Aug;62(8):1117–1133. [PubMed] [Google Scholar]
  34. Van Diest P.J., Baak J.P.A., Brugghe J., Van De Burg M.E.L., Van Oosterom A.T., Neijt J.P. Quantitative pathologic features as predictors of long-term survival in patients with advanced ovarian cancer treated with cisplatin. Int J Gynecol Cancer. 1994 May;4(3):174–179. doi: 10.1046/j.1525-1438.1994.04030174.x. [DOI] [PubMed] [Google Scholar]
  35. Voest E. E., van Houwelingen J. C., Neijt J. P. A meta-analysis of prognostic factors in advanced ovarian cancer with median survival and overall survival (measured with the log (relative risk)) as main objectives. Eur J Cancer Clin Oncol. 1989 Apr;25(4):711–720. doi: 10.1016/0277-5379(89)90208-3. [DOI] [PubMed] [Google Scholar]
  36. Zangwill B. C., Balsara G., Dunton C., Varello M., Rebane B. A., Hernandez E., Atkinson B. F. Ovarian carcinoma heterogeneity as demonstrated by DNA ploidy. Cancer. 1993 Apr 1;71(7):2261–2267. doi: 10.1002/1097-0142(19930401)71:7<2261::aid-cncr2820710716>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  37. van Diest P. J., Fleege J. C., Baak J. P. Syntactic structure analysis in invasive breast cancer: analysis of reproducibility, biologic background, and prognostic value. Hum Pathol. 1992 Aug;23(8):876–883. doi: 10.1016/0046-8177(92)90398-m. [DOI] [PubMed] [Google Scholar]
  38. van Houwelingen J. C., ten Bokkel Huinink W. W., van der Burg M. E., van Oosterom A. T., Neijt J. P. Predictability of the survival of patients with advanced ovarian cancer. J Clin Oncol. 1989 Jun;7(6):769–773. doi: 10.1200/JCO.1989.7.6.769. [DOI] [PubMed] [Google Scholar]

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