TSitologiya i Genetika 2020, vol. 54, no. 4, 93-95
Cytology and Genetics 2020, vol. 54, no. 4, 372–378, doi: https://www.doi.org/10.3103/S0095452720040064

Expression of Bcl­2 in imprint smears of endometrial carcinoma

Kosmas Konstantinos, Mitropoulou Georgia, Stamoulas Marios, Klapsinou Eirini, Marouga Anna

  1. Department of Cytopathology, General Chest Diseases Hospital of Athens “SOTIRIA”, Greece
  2. Pathology Department, “Agia Sofia” Children’s Hospital of Athens, Greece
  3. Department of Obstetrics & Gynaecology, Chesterfield Royal Hospital, Derbyshire, UK
  4. Department of Cytology, Diagnostic and Therapeutic Center of Athens “Hygeia”, Athens, Greece
  5. Department of Cytopathology, Athens University, Medical School, “Attikon” University Hospital, Athens, Greece

The aims of this study were to determine the expression of Bcl-2 in endometrial adenocarcinomas in imprint smears as an alternative technique rather than the frozen section and to correlate the results with clinicopathologic parameters of primary untreated endometrial cancer patients. One hundred twenty-six patients with endometrial carcinoma were evaluated with samples freshly resected after a total abdominal hysterectomy during a 29-month period. One hundred two cases were type I and 24 type II endometrial adenocarcinomas. Positive expression of Bcl-2 was observed only in type I and in low grade carcinomas. Immunocytochemical findings from Bcl-2 stain, appeared to be a valuable predictor of endometrial cancer diagnosis and postoperative prognosis in most cases in endometrial cytology with imprint smears. Furthermore, positive expression of Bcl-2 was related to morphologic features of less aggressiveness (pathogenetic type I, low-grade, early advanced stage, deep myometrial involvement <1/2 or not) tumors.

Keywords: Endometrial carcinoma, Bcl-2, imprint cytology, immunocytochemistry, endometrial cancer diagnosis

TSitologiya i Genetika
2020, vol. 54, no. 4, 93-95

Current Issue
Cytology and Genetics
2020, vol. 54, no. 4, 372–378,
doi: 10.3103/S0095452720040064

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1. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study, Global Burden of Disease Cancer Collaboration, JAMA Oncol., 2017, vol. 3, no. 4, pp. 524–548. PMID: 27918777. https://doi.org/10.1001/jamaoncol.2016.5688

2. Bokhman, J.V., Two pathogenetic types of endometrial carcinoma, Gynecol. Oncol., 1983, vol. 15, no. 1, pp. 10–17. PMID: 6822361.

3. Lax, S.F. and Kurman, R.J., A dualistic model for endometrial carcinogenesis based on immunohistochemical and molecular genetic analyses. Verh. Dtsch. Ges. Pathol., 1997, vol. 81, pp. 228–232. PMID: 9474874.

4. Blaustein’s Pathology of the Female Genital Tract, Kurman, R.J., Ed., 6th ed., New York: Springer, 2011, pp. 384–395.

5. Liu, F.S., Molecular carcinogenesis of endometrial cancer, Taiwan. J. Obstet. Gynecol., 2007, vol. 46, no. 1, pp. 26–32. PMID: 17389185. https://doi.org/10.1016/S1028-4559(08)60102-3

6. Lax, S.F., Pizer, E.S., Ronnett, B.M., and Kurman, R.J., Comparison of estrogen and progesterone receptor, Ki-67, and p53 immunoreactivity in uterine endometrioid carcinoma and endometrioid carcinoma with squamous, mucinous, secretory, and ciliated cell differentiation, Hum. Pathol., 1998, vol. 29, no. 9, pp. 924–931. PMID: 9744308.

7. Lax, S.F., Pizer, E.S., Ronnett, B.M., and Kurman, R.J., Clear cell carcinoma of the endometrium is characterized by a distinctive profile of p53, Ki-67, estrogen, and progesterone receptor expression, Hum. Pathol., 1998, vol. 29, no. 6, pp. 551–558. PMID: 9635673.

8. Hecht, J.L., Ince, T.A., Baak, J.P., Baker, H.E., Ogden, M.W., and Mutter, G.L., Prediction of endometrial carcinoma by subjective endometrial intraepithelial neoplasia diagnosis, Mod Pathol., 2005, vol. 18, no. 3, pp. 324–330. PMID: 15529181. https://doi.org/10.1038/modpathol.3800328

9. Mutter, G.L., Baak, J.P., Crum, C.P., Richart, R.M., Ferenczy, A., and Faquin, W.C., Endometrial precancer diagnosis by histopathology, clonal analysis, and computerized morphometry, J. Pathol., 2000, vol. 190, no. 4, pp. 462–469. PMID: 10699996. https://doi.org/10.1002/(SICI)1096-9896(200003)190:4<462::AID-PATH590>3.0CO;2-D

10. Oehler, M.K., Brand, A., and Wain, G.V., Molecular genetics and endometrial cancer, J. Br. Menopause Soc., 2003, vol. 9, no. 1, pp. 27–31. PMID: 12804310.

11. Osford, S.M., Dallman, C.L., Johnson, P.W., Ganesan, A., and Packham, G., Current strategies to target the anti-apoptotic Bcl-2 protein in cancer cells, Curr. Med. Chem., 2004, vol. 11, no. 8, pp. 1031–1039. PMID: 15083809.

12. Maia, H.Jr., Maltez, A., Studart, E., Athayde, C., and Coutinho, E.M., Ki-67, Bcl-2 and p53 expression in endometrial polyps and in the normal endometrium during the menstrual cycle, BJOG, 2004, vol. 111, no. 11, pp. 1242–1247. PMID: 15521869. https://doi.org/10.1111/j.1471-0528.2004.00406.x

13. Porichi, O., Nikolaidou, M.E., Apostolaki, A., Tserkezoglou, A., Arnogiannaki, N., Kassanos, D., Margaritis, L., and Panotopoulou, E., BCL-2, BAX and P53 expression profiles in endometrial carcinoma as studied by real-time PCR and immunohistochemistry, Anticancer Res., 2009, vol. 29, no. 10, pp. 3977–3982. PMID: 19846939.

14. Appel, M.L., Edelweiss, M.I., Fleck, J., Rivero, L.F., Rivoire, W.A., Mônego, H.I., and Dos Reis, R., P53 and BCL-2 as prognostic markers in endometrial carcinoma, Pathol. Oncol. Res., 2008, vol. 14, no. 1, pp. 23–30. PMID: 18398703. https://doi.org/10.1007/s12253-008-9000-9

15. Peiró, G., Diebold, J., Baretton, G.B., Kimmig, R., and Löhrs, U., Cellular apoptosis susceptibility gene expression in endometrial carcinoma: correlation with Bcl-2, Bax, and caspase-3 expression and outcome, Int. J. Gynecol. Pathol., 2001, vol. 20, no. 4, pp. 359–367. PMID: .11603220

16. Blaustein’s Pathology of the Female Genital Tract, Kurman, R.J., Ed., 6th ed., New York: Springer, 2011, pp. 394–395.

17. Blaustein’s Pathology of the Female Genital Tract, Kurman, R.J., Ed., 6th ed., New York: Springer, 2011, pp. 401–403.

18. Stewart, C.J., Brennan, B.A., Koay, E., Naran, A., and Ruba, S., Value of cytology in the intraoperative assessment of ovarian tumors: a review of 402 cases and comparison with frozen section diagnosis, Cancer Cytopathol., 2010, vol. 118, no. 3, pp. 127–136. PMID: 20544702. https://doi.org/10.1002/cncy.20073

19. Khalid, A. and Ul Haque, A., Touch impression cytology versus frozen section as intraoperative consultation diagnosis, Int. J. Pathol., 2004; vol. 2, no. 2, pp. 63–70.

20. Liu, Y., Silverman, J.F., Sturgis, C.D., Brown, H.G., Dabbs, D.J., and Raab, S.S., Utility of intraoperative consultation touch preparations, Diagn. Cytopathol., 2002, vol. 26, no. 5, pp. 329–333. PMID: 11992378. https://doi.org/10.1002/dc.10102

21. Kolte, S.S. and Satarkar, R.N., Role of scrape cytology in the intraoperative diagnosis of tumor, J. Cytol., 2010, vol. 27, no. 3, pp. 86–90. PMID: 21187882. https://doi.org/10.4103/0970-9371.71871

22. Rider, V., Progesterone and the control of uterine cell proliferation and differentiation, Front. Biosci., 2002, vol. 7, pp. 1545–1555. PMID: 12045023.

23. Elmore, S., Apoptosis: a review of programmed cell death, Toxicol. Pathol., 2007, vol. 35, no. 4, pp. 495–516. PMID: 17562483. https://doi.org/10.1080/01926230701320337

24. Bukholm, I.K. and Nesland, J.M., Protein expression of p53, p21 (WAF1/CIP1), bcl-2, Bax, cyclin D1 and pRb in human colon carcinomas, Virchows Arch., 2000, vol. 436, no. 3, pp. 224–228. PMID: 10782880.

25. Linjawi, A., Kontogiannea, M., Halwani, F., Edwardes, M., and Meterissian, S., Prognostic significance of p53, bcl-2, and Bax expression in early breast cancer, J. Am. Coll. Surg., 2004, vol. 198, no. 1, pp. 83–90. PMID: 14698315. https://doi.org/10.1016/j.jamcollsurg.2003.08.008

26. Vaskivuo, T.E., Stenbäck, F., and Tapanainen, J.S., Apoptosis and apoptosis-related factors Bcl-2, Bax, tumor necrosis factor-alpha, and NF-kappaB in human endometrial hyperplasia and carcinoma, Cancer, 2002, vol. 95, no. 7, pp. 1463–1471. PMID: 12237915. https://doi.org/10.1002/cncr.10876

27. Erkanli, S., Eren, F., Pekin, S., and Bagis, T. BCL-2 and P53 expression in endometrial carcinoma, J. Exp. Clin. Cancer Res., 2004, vol. 23, no. 1, pp. 97–103. PMID: 15149157.

28. Dobrzycka, B., Terlikowski, S.J., Garbowicz, M., Niklinski, J., Chyczewski, L., and Kulikowski, M., The prognostic significance of the immunohistochemical expression of P53 and BCL-2 in endometrial cancer, Folia Histochem. Cytobiol., 2011, vol. 49, no. 4, pp. 631–635. PMID: 22252757.

29. Kokawa, K., Shikone, T., Otani, T., Nishiyama, R., Ishii, Y., Yagi, S., and Yamoto, M., Apoptosis and the expression of Bax and Bcl-2 in hyperplasia and adenocarcinoma of the uterine endometrium, Hum. Reprod., 2001, vol. 16, no. 10, pp. 2211–2218. PMID: 11574518.

30. Sari, I., Gocmen, A., Bitiren, M., and Cakmak, E.A., The relationship between expression of p53/bcl-2 and clinicopathological criteria in endometrioid adenocarcinomas of the endometrium, Eur. J. Gynaecol. Oncol., 2004, vol. 25, no. 1, pp. 79–80. PMID: 15053067.

31. Kalogiannidis, I., Bobos, M., Papanikolaou, A., Makedos, A., Amplianitis, I., Vergote, I., Nenopoulou, E., and Makedos, G., Immunohistochemical bcl-2 expression, p53 overexpression, PR and ER status in endometrial carcinoma and survival outcomes, Eur. J. Gynaecol. Oncol., 2008, vol. 29, no. 1, pp. 19–25. PMID: 18386458.