DNA content evaluation for epithelial ovarian cancer identification

• Authors: António Tomé , Irene Leal , Carlos Palmeiras , Eduarda Matos , João Amado , Miguel Abreu , Carlos Lopes

Title variants

PL

Analiza zawartości DNA w rozpoznaniu nabłonkowego raka jajnika

• Languages of publication: EN

Abstracts

EN

Objective: To assess the cellular DNA status of epithelial ovarian cancer cells for clinical stage identification and its effect on survival. Methods: Sixty-two patients treated by primary surgery and six courses of platinum-based chemotherapy were enrolled. The surgical stage was analyzed in correlation with DNA ploidy, S-phase fraction and DNA index. DNA analysis was performed via image cytometry. Results: From the 62 cases, 38 were International Federation of Gynecology and Obstetrics (Fédération Internationale de Gynécologie et d’Obstétrique, FIGO) stage I and II, 24 – stage III and IV. In the DNA histograms obtained, the DNA index ranged from 0.85 to 3.02. Sixteen were classified as diploid and 46 as aneuploid (18 multiploid). S-phase fraction ranged from 9.8 to 51%. The aneuploid cells with DNA content above 5C ranged from 0.0 to 77.2%. Patients diagnosed with FIGO III and IV (vs. I and II) were 3.3 times more likely to die. Only in FIGO stage I and II the survival differed significantly for the different groups of ploidy. The risk of death for the multiploid (vs. diploid) group is 6.4 times and for aneuploid (vs. diploid) 2.3 times. Overall survival was better in the group with low DNA index. The low percentage compared with a high percentage of 5C cells ploidy groups showed association with mortality. The death hazard for the S-phase >33 median group is 4.9 times the hazard in relation to the S-phase <33. Conclusions: DNA ploidy, DNA index, S-phase, and 5C cells are important prognosticators for epithelial ovarian cancer mainly in early stages.

PL

Cel: Ocena statusu DNA komórek nabłonkowego raka jajnika w różnych stopniach zaawansowania klinicznego i jego wpływ na przeżycie. Metoda: Do badania zakwalifikowano 62 pacjentki leczone operacyjnie i za pomocą chemioterapii opartej na platynie (6 kursów). Stopień zaawansowania klinicznego nowotworu analizowano w odniesieniu do ploidalności DNA, frakcji fazy S oraz indeksu DNA. Analizę DNA przeprowadzono z zastosowaniem cytometrii obrazowej. Wyniki: Spośród 62 pacjentek 38 zakwalifikowano jako stopień zaawansowania I i II, natomiast 24 – jako stopień III i IV wg FIGO (International Federation of Gynecology and Obstetrics). W otrzymanych histogramach DNA indeks DNA wynosił 0,85–3,02. Szesnaście przypadków raka zaklasyfikowano jako diploidalne, natomiast 46 – jako aneuploidalne (18 multiploidalnych). Frakcja fazy S mieściła się w przedziale 9,8–51%. Odsetek komórek aneuploidalnych z zawartością DNA powyżej poziomu 5C wynosił 0,0–77,2%. Ryzyko śmierci było 3,3-krotnie większe w przypadku pacjentek z chorobą w stopniu zaawansowania FIGO III i IV (w porównaniu z I i II). Jedynie w przypadku stopni zaawansowania FIGO I i II odnotowano istotnie różnice w przeżywalności między poszczególnymi grupami ploidalności. Ryzyko śmierci było 6,4-krotnie większe w przypadku multiploidalności i 2,3-krotnie większe w przypadku aneuploidalności (w porównaniu z diploidalnością). Dłuższe przeżycie ogólne odnotowano w grupie o niskim indeksie DNA. Wykazano związek między niskim odsetkiem komórek 5C, w porównaniu z wysokim odsetkiem tych komórek w grupach poliploidalnych, a śmiertelnością. Ryzyko śmierci było 4,9-krotnie większe w grupie z medianą liczby komórek w fazie S >33 w porównaniu z medianą liczby komórek w fazie S <33. Wnioski: Ploidalność DNA, indeks DNA, faza S oraz obecność komórek 5C to ważne czynniki prognostyczne u pacjentek z nabłonkowym rakiem jajnika, głównie we wczesnym stadium.

Keywords

EN

DNA content; epithelial ovarian cancer; prognosis

Discipline

• MEDICINE: MEDICINE

• Journal: Current Gynecologic Oncology
• Year: 2018
• Volume: 16
• Issue: 1
• Pages: 3–10

Contributors

author

António Tomé

• Centre of Gynecological Oncology and Breast, Hospital Santo Antonio – Centro Hospitalar do Porto (CHP), Porto, Portugal

author

Irene Leal

• Department of Pathology, Hospital Santo Antonio – Centro Hospitalar do Porto (CHP), Porto, Portugal

author

Carlos Palmeiras

• Department of Immunology and Pathology, Portuguese Institute of Oncology (Instituto Português de Oncologia, IPO), Porto, Portugal

author

Eduarda Matos

• Ex-High Technician of Community Health, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Porto University, Portuga

author

João Amado

• Universidade Católica Portuguesa – Centre for Interdisciplinary Research in Health (Universidade Católica Portuguesa – Centro de Investigação Interdisciplinar em Saúde, UCP – CIIS), Porto, Portugal,

author

Miguel Abreu

• Department of Medicine (Oncology), Portuguese Institute of Oncology (Instituto Português de Oncologia, IPO), Porto, Portuga

author

Carlos Lopes

• Ex-Director of Department of Pathology, Hospital Santo António – Centro Hospitalar do Porto (CHP), Porto, Portugal

References

• 1. Kim YH, Kim SC: Recent advances in the biomarkers for epithelial ovarian cancer. J Gynecol Oncol 2011; 22: 219–221.
• 2. Chiang YC, Chen CA, Chiang CJ et al.: Trends in incidence and survival outcome of epithelial ovarian cancer: 30-year national population-based registry in Taiwan. J Gynecol Oncol 2013; 24: 342–351.
• 3. Vergote I: Prognostic factors in stage I ovarian carcinoma. Verh K Acad Geneeskd Belg 2001; 63: 257–271.
• 4. DiSilvestro P, Peipert JF, Hogan JW et al.: Prognostic value of clinical variables in ovarian cancer. J Clin Epidemiol 1997; 50: 501–505.
• 5. Clark TG, Stewart ME, Altman DG et al.: A prognostic model for ovarian cancer. Br J Cancer 2001; 85: 944–952.
• 6. Friedlander ML: Prognostic factors in ovarian cancer. Semin Oncol 1998; 25: 305–314.
• 7. Friedlander ML, Hedley DW, Taylor IW et al.: Influence of cellular DNA content on survival in advanced ovarian cancer. Cancer Res 1984; 44: 397–400.
• 8. Friedlander ML, Hedley DW, Swanson C et al.: Prediction of long-term survival by flow cytometric analysis of cellular DNA content in patients with advanced ovarian cancer. J Clin Oncol 1988; 6: 282–290.
• 9. Rice LW, Mark SD, Berkowitz RS et al.: Clinicopathologic variables, operative characteristics, and DNA ploidy in predicting outcome in ovarian epithelial carcinoma. Obstet Gynecol 1995; 86: 379–385.
• 10. Ozalp S, Yalcin OT, Gulbas Z et al.: Effect of cellular DNA content on the prognosis of epithelial ovarian cancers. Gynecol Obstet Invest 2001; 52: 93–97.
• 11. El-Naggar AK, Vielh P: Solid tumor DNA content analysis. Methods Mol Biol 2004; 263: 355–370.
• 12. Silvestrini R: Relevance of DNA-ploidy as a prognostic instrument for solid tumors. Ann Oncol 2000; 11: 259–261.
• 13. Coley HM, Sargent JM, Titley J et al.: Lack of prognostic significance of ploidy and S-phase measurements in advanced ovarian cancer. Anticancer Res 1999; 19: 2111–2116.
• 14. Winter WE 3rd, Maxwell GL, Tian C et al.; Gynecologic Oncology Group Study: Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2007; 25: 3621–3627.
• 15. Skirnisdóttir I, Sorbe B, Karlsson M et al.: Prognostic importance of DNA ploidy and p53 in early stages of epithelial ovarian carcinoma. Int J Oncol 2001; 19: 1295–1302.
• 16. Curling M, Stenning S, Hudson CN et al.: Multivariate analyses of DNA index, p62c-myc, and clinicopathological status of patients with ovarian cancer. J Clin Pathol 1998; 51: 455–461.
• 17. Schueler JA, Trimbos JB, vd Burg M et al.: DNA index reflects the biological behavior of ovarian carcinoma stage I–IIa. Gynecol Oncol 1996; 62: 59–66.
• 18. Kim YT, Zhao M, Kim SH et al.: Prognostic significance of DNA quantification by flow cytometry in ovarian tumors. Int J Gynaecol Obstet 2005; 88: 286–291.
• 19. Milczek T, Klasa-Mazurkiewicz D, Emerich J et al.: [Prognostic significance of Sphase fraction in ovarian cancer patients]. Ginekol Pol 2006; 77: 840–847.
• 20. Yoon BS, Kim YT, Kim S et al.: Prognostic value of nuclear DNA quantification and cyclin A expression in epithelial ovarian carcinoma. Eur J Obstet Gynecol Reprod Biol 2008; 136: 110–115.
• 21. Novik VI, Gevorkian VA, Maksimov SIa: [Prognostic significance of tumor cell ploidy in advanced ovarian carcinoma]. Vopr Onkol 2006; 52: 54–58.
• 22. Tropé CG, Abeler V, Baekelandt M et al.: [DNA ploidy in epithelial ovarian cancer – an independent prognostic factor]. Tidsskr Nor Laegeforen 2000; 120: 43–49.
• 23. Pietrzak K, Olszewski W: DNA ploidy as a prognostic factor in patients with ovarian carcinoma. Pol J Pathol 1998; 49: 141–144.
• 24. Lodhi S, Najam S, Pervez S: DNA ploidy analysis of borderline epithelial ovarian tumours. J Pak Med Assoc 2000; 50: 349–351.
• 25. Flezar MS, But I, Kavalar R et al.: Flow and image cytometric DNA ploidy, including 5c exceeding cells, of serous borderline malignant ovarian tumors. Correlation with clinicopathologic characteristics. Anal Quant Cytol Histol 2003; 25: 139–145.
• 26. Hwang J, Na S, Lee H et al.: Correlation between preoperative serum levels of five biomarkers and relationships between these biomarkers and cancer stage in epithelial ovarian cancer. J Gynecol Oncol 2009; 20: 169–175.
• 27. Oh J, Park SH, Lee TS et al.: High expression of epidermal growth factor-like domain 7 is correlated with poor differentiation and poor prognosis in patients with epithelial ovarian cancer. J Gynecol Oncol 2014; 25: 334–341.
• 28. Chiang AJ, Chen J, Chung YC et al.: A longitudinal analysis with CA-125 to predict overall survival in patients with ovarian cancer. J Gynecol Oncol 2014; 25: 51–57.
• 29. Klemi PJ, Joensuu H, Mäenpää J et al.: Influence of cellular DNA content on survival in ovarian carcinoma. Obstet Gynecol 1989; 74: 200–204.
• 30. Kaern J, Tropé CG, Kristensen GB et al.: Evaluation of deoxyribonucleic acid ploidy and S-phase fraction as prognostic parameters in advanced epithelial ovarian carcinoma: a prospective study. Am J Obstet Gynecol 1994; 170: 479–487.
• 31. Khoo SK, Hurst T, Kearsley J et al.: Prognostic significance of tumor ploidy in patients with advanced ovarian carcinoma. Gynecol Oncol 1990; 39: 284–288.
• 32. Wagner TMU, Adler A, Sevelda P et al.: Prognostic significance of cell DNA content in early-stage ovarian cancer (FIGO stages I and II/A) by means of automatic image cytometry. Int J Cancer 1994; 56: 167–172.
• 33. Gajewski WH, Fuller AF Jr, Pastel-Ley C et al.: Prognostic significance of DNA content in epithelial ovarian cancer. Gynecol Oncol 1994; 53: 5–12.
• 34. Pfisterer J, Kommoss F, Sauerbrei W et al.: Cellular DNA content and survival in advanced ovarian carcinoma. Cancer 1994; 74: 2509–2515.
• 35. Brescia RJ, Barakat RA, Beller U et al.: The prognostic significance of nuclear DNA content in malignant epithelial tumors of the ovary. Cancer 1990; 65: 141–147.
• 36. Resnik E, Trujillo YP, Taxy JB: Long-term survival and DNA ploidy in advanced epithelial ovarian cancer. J Surg Oncol 1997; 64: 299–303.
• 37. Reles AE, Gee C, Schellschmidt I et al.: Prognostic significance of DNA content and S-phase fraction in epithelial ovarian carcinomas analyzed by image cytometry. Gynecol Oncol 1998; 71: 3–13.
• 38. Yokoyama Y, Matsushita Y, Shigeto T et al.: Decreased ARID1A expression is correlated with chemoresistance in epithelial ovarian cancer. J Gynecol Oncol 2014; 25: 58–63.
• 39. Kallioniemi OP, Punnonen R, Mattila J et al.: Prognostic significance of DNA index, multiploidy, and S-Phase fraction in ovarian cancer. Cancer 1988; 61: 334–339.
• 40. Kang S, Kim TJ, Seo SS et al.: Prediction of a high-risk group based on postoperative nadir CA-125 levels in patients with advanced epithelial ovarian cancer. J Gynecol Oncol 2011; 22: 269–274.

• Document Type: article