Prognostic significance of clinic pathological and selected immunohistochemical factors in endometrial cancer

Česká verzia

Authors: I. Marková ¹; R. Pilka ²; M. Dušková ³; J. Zapletalová ⁴; Milan Kudela ²
Authors place of work: Ústav genetiky a fetální medicíny, FN a LF UP, Olomouc, přednosta prof. MUDr. J. Šantavý, CSc. ¹; Porodnicko-gynekologická klinika, FN a LF UP, Olomouc, přednosta doc. MUDr. R. Pilka, Ph. D. ²; Ústav patologické anatomie, FN a LF UP, Olomouc, přednosta doc. MUDr. M. Tichý, CSc. ³; Ústav lékařské biofyziky, pracoviště biometrie, LF UP, Olomouc, přednostka doc. RNDr. H. Kolářová, CSc. ⁴
Published in the journal: Ceska Gynekol 2010; 75(3): 193-199

Summary

Objective:
To assess the immunohistochemical expression of p53, bcl-2, c-erbB-2, Ki-67, estrogen (ER) and progesterone (PR) receptors in endometrial cancer patients. To assess the relation between steroid receptors positivity and other markers. To evaluate the prognostic significance of clinicopathologic and immunohistochemical markers on patient disease free survival.

Design:
Experimental prospective study.

Setting:
Department of Obstetrics and Gynaecology, Institute of Human Genetics, Department of Pathology, Department of Biophysics, Palacky University Medical School and University Hospital, Olomouc.

Methods:
We studied 144 cases of primary untreated endometrial carcinoma in which the p53, bcl-2, c‑erbB-2, Ki-67, ER and PR antigens were investigated with the use of an immunohistochemical method. In a group of 122 patients we assessed disease free survival (DFS) in relation to clinicopathologic and immunohistochemical factors.

Results:
From the total group of 144 patients, 122 were included for survival analysis. We found 15 (12,3%) patients with recurrence of the disease. Mean age was 64,5 (34-88) years. Immunohistologic expression was p53 positive in 29 (23,8%), bcl-2 positive in 87 (71,3%), c-erbB-2 positive in 34 (27,9%), Ki-67 positive in 56 (45,9%), ER positive in 97 (79,5%) and PR positive in 106 (86,9%) of cases.

In the survival analysis significantly shorter DFS was present in tumours with poor differentiation (G3), deep myometrial invasion (M2) and positive lymphoinvasion (N).

Conclusion:
Only poor differentiation (G3) and deep myometrial invasion (M2) are significant independent factors for the length of DFS.

Key words:
endometrial cancer, immunohistochemistry, prognostic factor, recurrence.

Zdroje

1. World cancer research fund: American Institute for Cancer Research: Food, Nutrition and the Prevention of Cancer: A global Perspective. Washington, DC, 1997.

2. Ascher, SM., Reinhold, C. Imaging of cancer of the endometrium. Radiol Clin North Am, 2002, 40, p. 563-576.

3. Canavan, TP., Doshi, NR. Endometrial cancer. Am Fam Physician, 1999, 59, p. 3069-3077.

4. Erdem, O., Erdem, M., Dursun, A., et al. Angiogenesis, p53, and bcl-2 expression as prognostic indicators in endometrial cancer: comparison with traditional clinicopathologic variables. Int J Gynecol Pathol, 2003, 22, p. 254-260.

5. Ferrandina, G., Ranelletti, FO., Gallotta, V., et al. Expression of cyclooxygenase-2 (COX-2), receptors for estrogen (ER), and progesterone (PR), p53, ki67, and neu protein in endometrial cancer. Gynecol Oncol, 2005, 98. p. 383-389.

6. Fitzgibbons, PL., Page, DL., Weaver, D., et al. Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med, 2000, 124, p. 966-978.

7. Gates, EJ., Hirschfield, L., Matthews, RP., et al. Body mass index as a prognostic factor in endometrioid adenocarcinoma of the endometrium. J Natl Med Assoc, 2006, 98, p. 1814-1822.

8. Geisler, JP., Geisler, HE., Wiemann, MC., et al. p53 expression as a prognostic indicator of 5-year survival in endometrial cancer. Gynecol Oncol, 1999, 74. p. 468-4671.

9. Geisler, JP., Wiemann, MC., Zhou, Z., et al. p53 as a prognostic indicator in endometrial cancer. Gynecol Oncol, 1996, 61, p. 245-248.

10. Goodman, MT., Wilkens, LR., Hankin, JH., et al. Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiol, 1997, 146, p. 294-306.

11. Halperin, R., Zehavi, S., Habler, L., et al. Comparative immunohistochemical study of endometrioid and serous papillary carcinoma of endometrium. Eur J Gynaecol Oncol, 2001, 22, p. 122-126.

12. Inoue, M. Current molecular aspects of the carcinogenesis of the uterine endometrium. Int J Gynecol Cancer, 2001, 11, p. 339-348.

13. Jalava, P., Kuopio, T., Huovinen, R., et al. Immunohistochemical staining of estrogen and progesterone receptors: aspects for evaluating positivity and defining the cutpoints. Anticancer Res, 2005, 25, p. 2535-2542.

14. Kadar, N., Malfetano, JH. , Homesley, HD. Steroid receptor concentrations in endometrial carcinoma: effect on survival in surgically staged patients, Gynecol Oncol, 1993, 50, p. 281-286.

15. Kodama, S., Kase, H., Tanaka, K., et al. Multivariate analysis of prognostic factors in patients with endometrial cancer. Int J Gynaecol Obstet, 1996, 53, p. 23-30.

16. Lax, SF., Pizer, ES., Ronnett, BM., et al. Clear cell carcinoma of the endometrium is characterized by a distinctive profile of p53, Ki-67, estrogen, and progesterone receptor expression. Hum Pathol, 1998, 29, p. 551-558.

17. Lu, KH., Broaddus, RR. Gynecologic cancers in Lynch syndrome/HNPCC. Fam Cancer, 2005, 4, p. 249-254.

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

19. Maneschi, M., Maneschi, F., Geraci, P., et al. Surgical pathological staging of endometrial carcinoma and results of treatment. Eur J Gynaecol Oncol, 1992, 13, p. 30-35.

20. Mariani, A., Sebo, TJ., Webb, MJ., et al. Molecular and histopathologic predictors of distant failure in endometrial cancer. Cancer Detect Prev, 2003, 27, p. 434-441.

21. Morris, PC., Anderson, JR., Anderson, B., et al. Steroid hormone receptor content and lymph node status in endometrial cancer. Gynecol Oncol, 1995, 56, p. 406-411.

22. Morrison, C., Zanagnolo, V., Ramirez, N., et al. HER-2 is an independent prognostic factor in endometrial cancer: association with outcome in a large cohort of surgically staged patients. J Clin Oncol, 2006, 24, p. 2376-2385.

23. Morrow, CP., Bundy, BN., Kurman, RJ., et al. Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol, 1991, 40, p. 55-65.

24. Ogawa, Y., Moriya, T., Kato, Y., et al. Immunohistochemical assessment for estrogen receptor and progesterone receptor status in breast cancer: analysis for a cut-off point as the predictor for endocrine therapy. Breast Cancer, 2004, 11, p. 267-275.

25. Ohkouchi, T., Sakuragi, N., Watari, H., et al. Prognostic significance of bcl-2, p53 overexpression, and lymph node metastasis in surgically staged endometrial carcinoma. Am J Obstet Gynecol, 2002, 187, p. 353-359.

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

27. Pijnenborg, JM., van de Broek, L., Dam de Veen, GC., et al. TP53 overexpression in recurrent endometrial carcinoma. Gynecol Oncol, 2006, 100, p. 397-404.

28. Pisani, AL., Barbuto, DA., Chen, D., et al. HER-2/neu, p53, and DNA analyses as prognosticators for survival in endometrial carcinoma. Obstet Gynecol, 1995, 85, p. 729-734.

29. Podczaski, E., Kaminski, P., Gurski, K., et al. Detection and patterns of treatment failure in 300 consecutive cases of “early” endometrial cancer after primary surgery. Gynecol Oncol, 1992, 47, p. 323-327.

30. Rose, PG. Endometrial carcinoma. N Engl J Med, 1996, 335, p. 640-649.

31. 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.

32. Salvesen, HB., Akslen, LA., Albrektsen, G., et al. Poorer survival of nulliparous women with endometrial carcinoma. Cancer, 1998, 82, p. 1328-1333.

33. Salvesen, HB., Iversen, OE., Akslen, LA. Identification of high-risk patients by assessment of nuclear Ki-67 expression in a prospective study of endometrial carcinomas. Clin Cancer Res, 1998, 4, p. 2779-2785.

34. Salvesen, HB., Iversen, OE., Akslen, LA. Prognostic significance of angiogenesis and Ki-67, p53, and p21 expression: a population-based endometrial carcinoma study. J Clin Oncol, 1999, 17, p. 1382-1390.

35. Santin, AD., Bellone, S., Roman, JJ., et al. Trastuzumab treatment in patients with advanced or recurrent endometrial carcinoma overexpressing HER2/neu, Int J Gynaecol Obstet, 2008, 102, p. 128-131.

36. ÚZIS, Novotvary ČR, 2005.

37. Yamauchi, N., Sakamoto, A., Uozaki, H., et al. Immunohistochemical analysis of endometrial adenocarcinoma for bcl-2 and p53 in relation to expression of sex steroid receptor and proliferative activity. Int J Gynecol Pathol, 1996, 15, p. 202‑208.

38. Zaino, RJ., Kurman, R., Herbold, D., et al. The significance of squamous differentiation in endometrial carcinoma. Data from a Gynecologic Oncology Group study. Cancer, 1991, 68, p. 2293‑2302.

39. Zaino, RJ., Kurman, RJ., Diana, KL., et al. Pathologic models to predict outcome for women with endometrial adenocarcinoma: the importance of the distinction between surgical stage and clinical stage – a Gynecologic Oncology Group study. Cancer, 1996, 77, p. 1115-1121.