Expression of apoptosis-related proteins in endometriomas and benign and malignant ovarian tumours

Apoptosis is a physiological process by which multicellular organisms eliminate superfluous cells. Alterations in apoptosis play a key role in tumour development. The objective was to evaluate the immunohistochemical expression of p53, p21, bax, bak, fas, bcl-2 and bcl-x proteins in 10 endometriomas, 20 benign ovarian tumours (10 mucinous, 10 serous) and 30 malignant ovarian tumours (9 mucinous, 19 serous; 2 endometrioids). p53 positive cells (mean±SD) in endometriomas, and benign and malignant tumours were 1.9±3.2, 0 and 16.2±33.0, respectively. The difference was significant between benign tumours and endometriomas (P=0.003) but not between endometriomas and malignant tumours. P21 expression in endometriomas and benign and malignant tumours was 19.5±27.8, 1.7±6.7 and 4.1±8.6, respectively. Increased p21 expression was found in endometriomas compared with benign (P=0.001) and malignant (P=0.01) tumours. Bax expression was higher in endometriomas than in benign tumours (P=0.01), but no difference was found between endometriomas and malignant tumours. No difference in bak, fas, bcl-2 or bcl-x expression was observed among the groups. In endometriomas, a negative correlation was found between p53 and fas expression (P=0.04, r=0.66). Although endometriomas have histological features of benign ovarian tumours, endometriomas share with malignant ovarian tumours certain alterations in apoptosis-related proteins. Similar content being viewed by others

Athanassiadou P, Petrakakou E, Sakelariou V, Zerva C, Liossi A, Michalas S, Athanassiades P (1998) Expression of p53, bcl-2 and heat shock protein (hsp72) in malignant and benign ovarian tumours. Eur J Cancer Prev 7:225–231 Attardi LD, Lowe SW, Brugarolas J, Jacks T (1996) Transcriptional activation by p53, but not induction of the p21 gene, is essential for oncogene-mediated apoptosis. EMBO J 15:3693–3701 Bayramoglu H, Duzcan E (2001) Atypical epithelial changes and mutant p53 gene expression in ovarian endometriosis. Pathol Oncol Res 7:33–38 Ben-Hur H, Gurevich P, Huszar M, et al (1999) Apoptosis and apoptosis-related proteins in the epithelium of human ovarian tumors: immunohistochemical and morphometric studies. Eur J Gynaecol Oncol 20:249–253 Brugarolas J, Chandrasekaran C, Gordon JI, Beach D, Jacks T, Hannon GJ (1995) Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature 377:552–557 Chan WY, Cheung KK, Schorge JO, et al (2000) Bcl-2 and p53 protein expression, apoptosis, and p53 mutation in human epithelial ovarian cancers. Am J Pathol 156:409–417 Chang CC, Hsieh YY, Tsai FJ, Tsai CH, Tsai HD, Lin CC (2002) The proline form of p53 codon 72 polymorphism is associated with endometriosis. Fertil Steril 77:43–45 Darai E, Bringuier AF, Walker-Combrouze F, Feldmann G, Madelenat P, Scoazec JY (1998) Soluble adhesion molecules in serum and cysts fluids from patients with cystic tumours of the ovary. Hum Reprod 13:2831–2835 Darai E, Leblanc M, Walker-Combrouze F, Bringuier AF, Madelenat P, Scoazec JY (1998) Expression of cadherins and CD44 isoforms in ovarian endometrial cysts. Hum Reprod 13:1346–1352 Deng C, Zhang P, Harper JW, Elledge SJ, Leder P (1995) Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell 82:675–684 Gottlieb TM, Oren M (1998) p53 and apoptosis. Semin Cancer Biol 8:359–368 Goumenou A, Panayiotides I, Matalliotakis I, Vlachonikolis I, Tzardi M, and Koumantakis E (2001) Bcl-2 and Bax expression in human endometriotic and adenomyotic tissues. Eur J Obstet Gynecol Reprod Biol 99:256–260 Harada M, Suganuma N, Furuhashi M, Nagasaka T, Nakashima N, Kikkawa F, Tomoda Y, Furui K (1996) Detection of apoptosis in human endometriotic tissues. Mol Hum Reprod 2:307–315 Heaps JM, Nieberg RK, Berek JS (1990) Malignant neoplasms arising in endometriosis. Obstet Gynecol 75:1023–1028 Hsieh YY, Tsai FJ, Chang CC, Chen WC, Tsai CH, Tsai HD, Lin CC (2001) p21 gene codon 31 arginine/serine polymorphism: non-association with endometriosis. J Clin Lab Anal 15:184–187 Hsu SY, Hsueh AJ (2000) Tissue-specific Bcl-2 protein partners in apoptosis: an ovarian paradigm. Physiol Rev 80:593–614 International Federation of Gynecology and Obstetrics (1971) Classification and staging of malignant tumours in the female pelvis. Acta Obstet Gynecol Scand 50:1–7 Jenkins S, Olive DL, Haney AF (1986) Endometriosis: pathogenetic implications of the anatomic distribution. Obstet Gynecol 67:335–338 Jones RK, Searle RF, Bulmer JN (1998) Apoptosis and bcl-2 expression in normal human endometrium, endometriosis and adenomyosis. Hum Reprod 13:3496–3502 Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257 Knudson CM, Tung KS, Tourtellotte WG, Brown GA, Korsmeyer SJ (1995) Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science 270:96–99 Kokawa K, Shikone T, Otani T, et al (2001) Apoptosis and the expression of bax and bcl-2 in hyperplasia and adenocarcinoma of the uterine endometrium. Hum Reprod 16:2211–2218 Lebovic DI, Mueller MD, Taylor RN (2001) Immunobiology of endometriosis. Fertil Steril 75:1–10 Marone M, Scambia G, Mozzetti S, et al (1998) Bcl-2, bax, bcl-xl, and bcl-xs expression in normal and neoplastic ovarian tissues. Clin Cancer Res 4:517–524 McCurrach ME, Connor TM, Knudson CM, Korsmeyer SJ, Lowe SW (1997) Bax-deficiency promotes drug resistance and oncogenic transformation by attenuating p53-dependent apoptosis. Proc Natl Acad Sci U S A 94:2345–2349 McLaren J, Prentice A, Charnok-Jones DS, Sharkey AM, Smith SK (1997) Immunolocalization of the apoptosis regulating proteins bcl-2 and bax in human endometrium and isolated peritoneal fluid macrophages in endometriosis. Hum Reprod 12:146–152 Meresman GF, Vighi S, Buquet RA, Contreras-Ortiz O, Tesone M, Rumi LS (2000) Apoptosis and expression of Bcl-2 and Bax in eutopic endometrium from women with endometriosis. Fertil Steril 74:760–766 Nagata S (1994) Fas and Fas ligand: a death factor and its receptor. Adv Immunol 57:129–144 Nakayama K, Toki T, Zhai YL, Lu X, Horiuchi A, Nikaido T, Konishi I, Fujii S (2001) Demonstration of focal p53 expression without genetic alterations in endometriotic lesions. Int J Gynecol Pathol 20:227–231 Nezhat FR, Kalir T (2002) Comparative immunohistochemical studies of endometriosis lesions and endometriotic cysts. Fertil Steril 78:820–824 Nezhat F, Cohen C, Rahaman J, Gretz H, Cole P, Kalir T (2002) Comparative immunohistochemical studies of bcl-2 and p53 proteins in benign and malignant ovarian endometriotic cysts. Cancer 94:2935–2940 Owen-Schaub LB, Zhang W, Cusack JC, et al (1995) Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression. Mol Cell Biol 15:3032–3040 Ridley JH (1968) The histogenesis of endometriosis. A review of facts and fancies. Obstet Gynecol 23:1–35 Ryan IP, Taylor RN (1997) Endometriosis and infertility: new concepts. Obstet Gynecol Surv 52:365–371 Sampson JA (1927) Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 14:422–469 Schneider J, Jimenez E, Rodriguez F, del Tanago JG (1998) c-myc, c-erb-B2, nm23 and p53 expression in human endometriosis. Oncol Rep 5:49–52 Stovall DW, Bowser LM, Archer DF, Guzick DS (1997) Endometriosis-associated pelvic pain: evidence for an association between the stage of disease and a history of chronic pelvic pain. Fertil Steril 68:13–18 Suganuma N, Harada M, Furuhashi M, Nawa A, Kikkawa F (1997) Apoptosis in human endometrial and endometriotic tissues. Horm Res 48:42–47 Vaux Dl, Cory S, Adams JM (1988) Bcl-2 gene promotes haematopoetic cell survival and co-operates with c-myc to immortalize pre-B cells. Nature 335:440–442 Vercellini P, Trespidi L, De Giorgi O (1996) Endometriosis and pelvic pain: relation to disease stage and localization. Fertil Steril 65:299–304 Vogt J (1872) Untersuchungen uber die Entwicklungsgeschichte der Geburtshelferkroete (Alytes obstetricians). Jent & Gassman, Solothurn, Switzerland Watanabe H, Kanzaki H, Narukawa S, Inoue T, Katsuragawa H, Kaneko Y, and Mori T (1997) Bcl-2 and Fas expression in eutopic and ectopic human endometrium during the menstrual cycle in relation to endometrial cell apoptosis. Am J Obstet Gynecol 176:360–368 Werness BA, Freedman AN, Piver MS, Romero-Gutierrez M, Petrow E (1999) Prognostic significance of p53 and p21(waf1/cip1) immunoreactivity in epithelial cancers of the ovary. Gynecol Oncol 75:413–418 Yin C, Knudson CM, Korsmeyer SJ, Van Dyke T (1997) Bax suppresses tumorigenesis and stimulates apoptosis in vivo. Nature 385:637–640 Zusman I, Gurevich P, Gurevich E, Ben-Hur H (2001) The immune system, apoptosis and apoptosis-related proteins in human ovarian tumors (a review). Int J Oncol 18:965–972 Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Fauvet, R., Poncelet, C., Hugol, D. et al. Expression of apoptosis-related proteins in endometriomas and benign and malignant ovarian tumours. Virchows Arch 443, 38–43 (2003). https://doi.org/10.1007/s00428-003-0813-3 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00428-003-0813-3