Prognostic importance of selected molecular genetic immunohistochemical markers and DNA ploidy in endometrial cancer

Czech version

Authors: Milan Kudela ¹; R. Pilka ¹; M. Lubušký ¹; P. Hejtmánek ¹; P. Džubák ²; S. Brychtová ³
Authors‘ workplace: Porodnicko-gynekologická klinika LF UP a FN Olomouc, přednosta doc. MUDr. R. Pilka, Ph. D. ¹; Laboratoř experimentální medicíny, Ústav molekulární a transplantační medicíny, LF UP a FN Olomouc ²; Ústav patologie LF UP a FN Olomouc ³
Published in: Ceska Gynekol 2011; 76(3): 194-199

Overview

Objective:
The aim of the study was the analysis of the new molecular genetic immunomarkers (p53, c‑erbB-2, Ki 67, bcl-2) hormonal receptors (ER, PR) and ploidy disturbances and their relation to the most important prognostic factors for endometrial cancer.

Design:
Prospective study.

Setting:
Dept. of Gynaecology and Obsterics, Laboratory of Experimental Medicine, Institute of Pathology, Institute of Molecular and Transplational Medicine, Medical Faculty and University Hospital, Olomouc.

Methods:
The study group consisted of 88 endometrial cancer patients. The biopsies of the tumours obtained at operations were routinely histopathologically examined. Subsequently, the immunohistochemical tumormarkers were determined. The same biopsies were examined by microdissection and flow cytometric ploidy analysis and karyotyping. The findings were compared with the most important prognostic factors for endometrial cancer, mainly with clinical stage of the disease, grade and histopathological type.

Results:
Aneuploidy was found in 71% in the group of poorly differentiated endometrial cancers (G3) in contrast to 47% in the group of G1 and G2 tumours. High expression of p53, Ki 67, c-erbB-2 and low rate of sex hormone receptors was found in the prognostically unfavourable group (G3).

Conclusions:
Aneuploidy seems to be an important prognostical factor for endometrial cancer patients. Identification of p53, Ki 67, c-erbB-2, ER a PR is a useful tool to specify a group of prognostically unfavourable patients.

Key words:
endometrial cancer, DNA ploidy, molecular immunomarkers, prognostic factors.

Sources

1. Erdem O., Erdem M., Dursum A., et al. Angiogenesis, p 53 and bcl-2 expression as prognostic indicators in endometrial cancer: Comparison with traditional clinicopathological variables. Int J Gynecol Pathol, 2003, 22, p. 254-260.

2. FIGO committee on gynecologic oncology. Revised FIGO staging for carcinoma of the vulva, cervix and endometrium. Int J Gyn Obstet, 105, 2009, p. 103-104.

3. Ferrandina, G., Ranelletti, FO., Gallotta, V., et al. Expression of cyclooxygenase-2 (COX-2), receptors for estrogen (ER) and progesteron (PR), p 53, Ki-67, and neu protein in endometrial cancer. Gynecol Oncol, 2005, 98, p. 383-389.

4. Freiberg, LG., Norén, H., Delle, U. Prognostic value of DNA ploidy and S-phase fraction in endometrial cancer stage I and II: a prospective 5-year survival study. Gynecol Oncol, 1994, 53, 1, p. 64-69.

5. Fu, YS., Gambone, JC., Berek, JS. Pathophysiology and management of endometrial hyperplasia and carcinoma. West J Med, 1990, 153, 1, p. 50-61.

6. Cherchi, PM., Madras, V., Capobiano, G., et al. Prognostic value of p53, c-erb-B2 and MIB-1 in endometrial carcinoma. Eur J Gynaecol Oncol, 2001, 22, p. 451-453.

7. Gassel, A., Backe, J., Krebs, S., et al. Endometrial carcinoma: immunohiostochemically detected proliferation index is a prognosticator of long-term outcome. J Clin Pathol, 1998, 51, p. 25-29.

8. Graesslin, O., Chanát-Bastaraud, S., Lorenzato, M., et al. Fluorescence in situ hybridization and immunohistochemical analysis of p53 expression in endometrial cancer: prognostic value and relation to ploidity. Ann Surg Oncol, 2008, 15, p. 484-492.

9. Halperin, R., Zehavi, S., Hamer, L., et al. Comaparative immunohistochemical study of endometritid and serous papillary carcinoma of endometrium. Eur J Gynecol Oncol, 2001, 22, p. 122-126.

10. Jazaeri, AA., Nunes, KJ., Dalton, MS., et al. Well – differentiated endometrial adenocarcinomas and poorly differentiated mixed Mullerian tumors have altered ER and PR isoform expression. Oncogene, 2001, 20, p. 6965-6969.

11. Larson, DM., Berg, R., Show, G., Krawisz, BR. Prognostic significance of DNA ploidy in endometrial cancer. Gynecol Oncol, 1999, 74, 3, p. 356-360.

12. Lindahl, B., Alm, P., Ferno, M., et al Prognostic value of flow cytometrical DNA measurements in stage I-II endometrial carcinoma: Correlations with steroid receptor concentration, tumor myometrial invasion and degrese of differentiation. Anticancer Res, 1987, 7, p. 791-798.

13. Lukes, AS., Kohler, MF., Pieper, CF., et al. Multivariable analysis od DNA ploidity, p53 and HER-2/neu as prognostic factors in endometrial cancer. Cancer, 1994, 73, 9, p. 2380-2385.

14. Lundgren, C., Lahmann, J., Beder, S., Roblick, U. 2-DE protein expression in endometrial carcinoma. Acta Oncol, 2006, 45, p. 685-694.

15. Mangili, G., De Marzi, P., Viganň, R., et al. Identification of high risk patients with endometrial carcinoma. Prognostic assesment of endometrial cancer. Eur J Gynaecol Oncol, 2002, 23, 3, p. 216-220.

15. Mangili, G., Montoli, S., De Marzi, P., et al. The role of DNA ploidy in postoperative managenemnt of stage I endometrial cancer. Ann Oncol, 2008, 19, p. 1278-1283.

16. Marková, I., Pilka, R., Dušková, M., et al. Prognostický význam klinickopatologických a vybraných imunohistochemických faktorů u karcinomu endometria. Čes Gynek, 2010, 75, 3, s. 193-199.

17. Mariani, A., Sebo, TJ., Katzmann, JA., Keeney, GL. Pretreatment assessment of prognostic indicators in endometrial cancer. Am J Obstet Gynecol, 2000, 182, p. 1535-1544.

18. Mariani, A., Conti, L., Antenucci, A., Vecillo, M. Predictive value of cell kinetics in endometrial adenocarcinoma. Anticancer Res, 2000, 20, p. 3569-3574.

19. Mariani, A., Sebo, TJ., Webb, MJ., Riehle, D. Molecular and histopatologic predictors of distant failure in endometrial cancer. Cancer Detect Prev, 2003, 27, p. 434-441.

20. Melchiorri, C., Chieco, P., Lisignoli, G., et al. Ploidy disturbances as an early indicator of intrinsic malignancy in endometrial carcinoma. Cancer, 1993, 72, 1, p. 165-172.

21. Mičková, I., Pilka, R., Lubušký, M., Kudela, M. Molekulární prognostické faktory a patogeneze endometriáního karcinomu. Čes Gynek, 2006, 71, s. 355-360.

22. Oehler, MK., Rees, MC., Bicknell, R. Steroids and the endometrium. Curr Med Chem, 2000, p. 543-560.

23. Owen, P., Duncan, ID. Is there any value in long term follow up of women treated for endometrial cancer? Br J Obstet Gynaecol, 1996, 103, p. 710-713.

24. Pfisterer, J., Kommoss, F., Sauerbrei, W., et al. Prognostic value of DNA ploidy and S-phase fraction in stage I endometrial carcinoma. Gynecol Oncol, 1995, 58, 2, p. 149-156.

25. Riben, MW., Malfetano, JH., Nazeer, T., et al. Identification of HER-2/neu oncogene amplification by fluorescence in situ hybridization in stage I endometrial carcinoma. Mod Pathol, 1997, 10, p. 823-831.

26. Sakuragi, N., Ohkouchi, T., Hareyama, H., et al. Bcl-2 expression and prognosis of patients with endometrial carcinoma. Int J Cancer, 1998, 79, p. 153-158.

27. Salvesen, HB., Iversen, OE., Allen, LA. Identification of high-risk patients by assessment of nuclear Ki-67 exprassion in aprospective study of endometrial carcinomas. Clin Cancer Res, 1998, 4, p. 2779-2785.

28. Salvesen, HB., Iversen, OE, Allen, LA. Prognostic signifikance of angiogenesis and Ki-67, p53 and p21 expression: apopulation-based endometrial carcinoma study. J Clin Oncol, 1999, 17, p. 1382-1390.

29. Shimizu, K. Prognostic evaluation of endometrial carcinoma by DNA content and histologic factors. Nippon Sanka Fininka gakkai Zasshi, 1995, 47, 4, p.413-418.

30. Skirnisdóttir, I., Sorbe, B., Karisson, M., Seidal, T. Prognostic importace of DNA ploidy and p53 in early stages of epithelial ovarian carcinoma. Int J Oncol, 19, 2001, p. 1295-1302.

31. Susini, T., Amunni, G., Molino, C., et al. Ten-year results of a prospective study on the prognostic role of ploidy in endometrial carcinoma: DNA aneuploidy identifies high-risk cases among the so–called „low – risk“ patients with well and moderately differentiated tumors. Cancer, 2007, 109, 5, p. 882‑890.

32. Thornton, JG., Ali, S., O’Donovan, P., et al. Flow cytometric studie of ploidy and proliferative indicies in the Yorkshire trial of adjuvant progesteron treatment of endometrial cancer. Br J Obstet Gynaecol, 1993, 100, p. 253-261.

33. von Minckwitz, G., Kun, W., Kaufmann, M., et al. Prognostic importace of DNA-ploidy and S-phase fractio in endometrial cancer. Int J Gynecol Cancer, 1994, 4, p. 250-256.

34. Wimberger, P., Hillemanns, P., Kapsner, T., et al. Evaluation of prognostic factors following flow-cytometric DNA analysis after cytokeratin labelling: II. Cervical and endometrial cancer. Anal Cell Pathol, 2002, 24, p. 147-148.