nach oben

Erschienen in:

01.07.2011 | Gynecologic Oncology

Inhibin/activin-betaC subunit does not represent a prognostic parameter in human endometrial cancer

verfasst von: Stefanie D. Käufl, Christina Kuhn, Susanne Kunze, Naim Shabani, Ansgar Brüning, Klaus Friese, Ioannis Mylonas

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

Introduction

Inhibins, dimeric peptide hormones composed of an α subunit and one of two possible β subunits (betaA or betaB), exhibit substantial roles in human reproduction and in endocrine-responsive tumors. Recently, two novel inhibin-beta subunits, defined as betaC and betaE, have been identified in humans. However, the prognostic significance and clinical implications of the novel inhibin-betaC subunit in endometrial cancers is still quite unclear.

Materials and methods

A series of 296 uterine endometrial carcinomas were immunohistochemically analyzed with specific antibody against the inhibin-betaC subunit. The staining reactions were correlated with several clinicopathological characteristics and the clinical outcome.

Results

Endometrial cancer tissue demonstrated an immunolabelling against the inhibin-betaC subunit. The inhibin-betaC expression in endometrial carcinoma samples revealed a significant association with hemangiosis. However, the expression of this inhibin subunit did not affect patients’ progression-free, cause-specific and overall survival.

Conclusion

Overall, inhibin-betaC subunit was demonstrated in endometrial cancer tissue. This novel betaC subunit demonstrated a significant association with hemangiosis although without any impact on the patients’ survival. Moreover, the inhibin-betaC subunits did not constitute an independent prognostic parameter in endometrial cancer patients. Therefore, the isolated analysis of this subunit might be of minor prognostic value in identifying high-risk patients.

Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I (2005) Endometrial cancer. Lancet 366(9484):491–505PubMedCrossRef

Prat J (2004) Prognostic parameters of endometrial carcinoma. Hum Pathol 35(6):649–662PubMedCrossRef

Jereczek-Fossa B, Badzio A, Jassem J (1999) Surgery followed by radiotherapy in endometrial cancer: analysis of survival and patterns of failure. Int J Gynecol Cancer 9(4):285–294PubMedCrossRef

Sayin NC, Varol FG, Yuce MA, Kaplan P, Ahmet N, Sut N, Gucer F (2009) Do routine preoperative imaging techniques facilitate the operation in endometrial cancer? Arch Gynecol Obstet 280(2):211–215. doi:10.1007/s00404-008-0893-z PubMedCrossRef

Lax SF (2004) Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification. Virchows Arch 444(3):213–223PubMedCrossRef

Mylonas I, Worbs S, Shabani N, Kuhn C, Kunze S, Schulze S, Dian D, Gingelmaier A, Schindlbeck C, Bruning A, Sommer H, Jeschke U, Friese K (2009) Inhibin-alpha subunit is an independent prognostic parameter in human endometrial carcinomas: analysis of inhibin/activin-alpha, -betaA and -betaB subunits in 302 cases. Eur J Cancer 45(7):1304–1314. doi:S0959-8049(09)00002-1[pii]10.1016/j.ejca.2009.01.008 PubMedCrossRef

Worbs S, Shabani N, Mayr D, Gingelmaier A, Makrigiannakis A, Kuhn C, Jeschke U, Kupka MS, Friese K, Mylonas I (2007) Expression of the inhibin/activin subunits (-alpha, -betaA and -betaB) in normal and carcinogenic endometrial tissue: possible immunohistochemical differentiation markers. Oncol Rep 17(1):97–104PubMed

Xia Y, Schneyer AL (2009) The biology of activin: recent advances in structure, regulation and function. J Endocrinol 202(1):1–12. doi:JOE-08-0549[pii]10.1677/JOE-08-0549 PubMedCrossRef

Vale W, Wiater E, Gray P, Harrison C, Bilezikjian L, Choe S (2004) Activins and inhibins and their signaling. Ann N Y Acad Sci 1038:142–147

10.

Risbridger GP, Ball EM, Wang H, Mellor SL, Peehl DM (2004) Re-evaluation of inhibin alpha subunit as a tumour suppressor in prostate cancer. Mol Cell Endocrinol 225(1–2):73–76PubMedCrossRef

11.

Matzuk MM, Finegold MJ, Su JG, Hsueh AJ, Bradley A (1992) Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature 360(6402):313–319PubMedCrossRef

12.

Matzuk MM, Finegold MJ, Mather JP, Krummen L, Lu H, Bradley A (1994) Development of cancer cachexia-like syndrome and adrenal tumors in inhibin-deficient mice. Proc Natl Acad Sci USA 91(19):8817–8821PubMedCrossRef

13.

Mylonas I, Makovitzky J, Richter DU, Jeschke U, Briese V, Friese K (2004) Expression of the inhibin-alpha subunit in normal, hyperplastic and malignant endometrial tissue: an immunohistochemical analysis. Gynecol Oncol 93(1):92–97PubMedCrossRef

14.

Hötten G, Neidhardt H, Schneider C, Pohl J (1995) Cloning of a new member of the TGF-beta family: a putative new activin beta C chain. Biochem Biophys Res Commun 206(2):608–613CrossRef

15.

Fang J, Yin W, Smiley E, Wang SQ, Bonadio J (1996) Molecular cloning of the mouse activin beta E subunit gene. Biochem Biophys Res Commun 228(3):669–674PubMedCrossRef

16.

Weissenbacher T, Bruning A, Kimmich T, Makovitzky J, Gingelmaier A, Mylonas I (2010) Immunohistochemical Labeling of the Inhibin/activin betaC subunit in normal human placental tissue and chorionic carcinoma cell lines. J Histochem Cytochem 58(8):751–757. doi:jhc.2010.956185[pii]10.1369/jhc.2010.956185

17.

Mylonas I, Shabani N, Vogl J, Makovitzky J, Kunze S, Kuhn C, Schulze S, Friese K, Jeschke U (2007) Inhibin/activin subunits are immunohistochemically expressed in complete and partial hydatidiform moles. Anticancer Res 27(4A):1995–2000

18.

Gingelmaier A, Bruning A, Kimmich T, Makovitzky J, Bergauer F, Schiessl B, Friese K, Mylonas I (2010) Inhibin/activin-betaE subunit is expressed in normal and pathological human placental tissue including chorionic carcinoma cell lines. Arch Gynecol Obstet. doi:10.1007/s00404-009-1340-5

19.

Kimmich T, Bruning A, Kaufl SD, Makovitzky J, Kuhn C, Jeschke U, Friese K, Mylonas I (2010) Inhibin/activin-betaC and -betaE subunits in the Ishikawa human endometrial adenocarcinoma cell line. Arch Gynecol Obstet 282(2):185–191. doi:10.1007/s00404-009-1310-y PubMedCrossRef

20.

Käufl SD, Makovitzky J, Kuhn C, Kunze S, Jeschke U, Mylonas I (2010) Inhibin/activin-betaC subunit in human endometrial adenocarcinomas and HEC-1a adenocarcinoma cell line. In Vivo (in press)

21.

Shabani N, Kuhn C, Kunze S, Schulze S, Mayr D, Dian D, Gingelmaier A, Schindlbeck C, Willgeroth F, Sommer H, Jeschke U, Friese K, Mylonas I (2007) Prognostic significance of oestrogen receptor alpha (ERalpha) and beta (ERbeta), progesterone receptor A (PR-A) and B (PR-B) in endometrial carcinomas. Eur J Cancer 43(16):2434–2444. doi:S0959-8049(07)00642-9[pii]10.1016/j.ejca.2007.08.014 PubMedCrossRef

22.

Anonymous (1989) FIGO stages (announcements). Gynecol Oncol 35125–35127

23.

Mylonas I, Jeschke U, Wiest I, Hoeing A, Vogl J, Shabani N, Kuhn C, Schulze S, Kupka MS, Friese K (2004) Inhibin/activin subunits alpha, beta-A and beta-B are differentially expressed in normal human endometrium throughout the menstrual cycle. Histochem Cell Biol 122(5):461–471PubMedCrossRef

24.

Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53457–53481

25.

Cox DR (1972) Regression models and life tables. J R Stat Soc B 34187–34220

26.

Ehata S, Hanyu A, Fujime M, Katsuno Y, Fukunaga E, Goto K, Ishikawa Y, Nomura K, Yokoo H, Shimizu T, Ogata E, Miyazono K, Shimizu K, Imamura T (2007) Ki26894, a novel transforming growth factor-beta type I receptor kinase inhibitor, inhibits in vitro invasion and in vivo bone metastasis of a human breast cancer cell line. Cancer Sci 98(1):127–133PubMedCrossRef

27.

Ogino H, Yano S, Kakiuchi S, Muguruma H, Ikuta K, Hanibuchi M, Uehara H, Tsuchida K, Sugino H, Sone S (2008) Follistatin suppresses the production of experimental multiple-organ metastasis by small cell lung cancer cells in natural killer cell-depleted SCID mice. Clin Cancer Res 14(3):660–667PubMedCrossRef

28.

Tsuchida K, Nakatani M, Hitachi K, Uezumi A, Sunada Y, Ageta H, Inokuchi K (2009) Activin signaling as an emerging target for therapeutic interventions. Cell Commun Signal 7:15. doi:1478-811X-7-15[pii]10.1186/1478-811X-7-15

29.

Mylonas I, Jeschke U, Winkler L, Makovitzky J, Richter DU, Briese V, Friese K (2003) Immunohistochemical expression of inhibin-alpha in human endometrium and the in vitro secretion of inhibin, estradiol and cortisol in cultured human endometrial glandular cells. Arch Gynecol Obstet 268(3):142–150. doi:10.1007/s00404-003-0526-5 PubMedCrossRef

30.

Vogl J, Hoing A, Schulze S, Kuhn C, Wiest I, Shabani N, Jeschke U, Mylonas I, Friese K (2007) Expression of inhibins in the endometrial carcinoma cell line RL-95-2 after stimulation with cortisol and estradiol. Anticancer Res 27(4A):1989–1993

31.

Mylonas I, Makovitzky J, Fernow A, Richter DU, Jeschke U, Briese V, Gerber B, Friese K (2005) Expression of the inhibin/activin subunits alpha (alpha), beta-A (betaA) and beta-B (betaB) in benign human endometrial polyps and tamoxifen-associated polyps. Arch Gynecol Obstet 272(1):59–66. doi:10.1007/s00404-004-0666-2 PubMedCrossRef

32.

Risbridger GP, Schmitt JF, Robertson DM (2001) Activins and inhibins in endocrine and other tumors. Endocr Rev 22(6):836–858PubMedCrossRef

33.

Mylonas I (2010) Inhibin-alpha, -betaA and -betaB subunits in uterine non-endometrioid carcinomas: prognostic significance and clinical implications. Eur J Cancer. doi:S0959-8049(10)00476-4[pii]10.1016/j.ejca.2010.06.001

34.

Sharifi N, Lechleider RJ, Farrar WL (2007) Transforming growth factor-beta receptor III downregulation in prostate cancer: is inhibin B a tumor suppressor in prostate? J Mol Endocrinol 39(5):329–332PubMedCrossRef

35.

Chabicovsky M, Herkner K, Rossmanith W (2003) Overexpression of activin beta(C) or activin beta(E) in the mouse liver inhibits regenerative deoxyribonucleic acid synthesis of hepatic cells. Endocrinology 144(8):3497–3504PubMedCrossRef

36.

Vejda S, Erlach N, Peter B, Drucker C, Rossmanith W, Pohl J, Schulte-Hermann R, Grusch M (2003) Expression of activins C and E induces apoptosis in human and rat hepatoma cells. Carcinogenesis 24(11):1801–1809PubMedCrossRef

37.

Wada W, Medina JJ, Kuwano H, Kojima I (2005) Comparison of the function of the beta(C) and beta(E) subunits of activin in AML12 hepatocytes. Endocr J 52(2):169–175PubMedCrossRef

38.

Gold EJ, Zhang X, Wheatley AM, Mellor SL, Cranfield M, Risbridger GP, Groome NP, Fleming JS (2005) betaA- and betaC-activin, follistatin, activin receptor mRNA and betaC-activin peptide expression during rat liver regeneration. J Mol Endocrinol 34(2):505–515PubMedCrossRef

39.

Lau AL, Kumar TR, Nishimori K, Bonadio J, Matzuk MM (2000) Activin betaC and betaE genes are not essential for mouse liver growth, differentiation, and regeneration. Mol Cell Biol 20(16):6127–6137PubMedCrossRef

40.

Gold E, Jetly N, O’Bryan MK, Meachem S, Srinivasan D, Behuria S, Sanchez-Partida LG, Woodruff T, Hedwards S, Wang H, McDougall H, Casey V, Niranjan B, Patella S, Risbridger G (2009) Activin C antagonizes activin A in vitro and overexpression leads to pathologies in vivo. Am J Pathol 174(1):184–195. doi:ajpath.2009.080296[pii]10.2353/ajpath.2009.080296 PubMedCrossRef

41.

Mellor SL, Cranfield M, Ries R, Pedersen J, Cancilla B, de Kretser D, Groome NP, Mason AJ, Risbridger GP (2000) Localization of activin beta(A)-, beta(B)-, and beta(C)-subunits in humanprostate and evidence for formation of new activin heterodimers of beta(C)-subunit. J Clin Endocrinol Metab 85(12):4851–4858PubMedCrossRef

42.

Mellor SL, Ball EM, O’Connor AE, Ethier JF, Cranfield M, Schmitt JF, Phillips DJ, Groome NP, Risbridger GP (2003) Activin betaC-subunit heterodimers provide a new mechanism of regulating activin levels in the prostate. Endocrinology 144(10):4410–4419PubMedCrossRef

43.

Razanajaona D, Joguet S, Ay AS, Treilleux I, Goddard-Leon S, Bartholin L, Rimokh R (2007) Silencing of FLRG, an antagonist of activin, inhibits human breast tumor cell growth. Cancer Res 67(15):7223–7229PubMedCrossRef

44.

Ramachandran A, Marshall ES, Love DR, Baguley BC, Shelling AN (2009) Activin is a potent growth suppressor of epithelial ovarian cancer cells. Cancer Lett 285(2):157–165. doi:S0304-3835(09)00344-9[pii]10.1016/j.canlet.2009.05.010 PubMedCrossRef

45.

Katik I, Mackenzie-Kludas C, Nicholls C, Jiang FX, Zhou S, Li H, Liu JP (2009) Activin inhibits telomerase activity in cancer. Biochem Biophys Res Commun 389(4):668–672. doi:S0006-291X(09)01857-9[pii]10.1016/j.bbrc.2009.09.055

46.

Di Simone N, Schneyer AL, Caliandro D, Castellani R, Caruso A (2002) Regulation of endometrial adenocarcinoma cell proliferation by Activin-A and its modulation by 17beta-estradiol. Mol Cell Endocrinol 192(1–2):187–195PubMedCrossRef

Titel: Inhibin/activin-betaC subunit does not represent a prognostic parameter in human endometrial cancer
verfasst von: Stefanie D. Käufl
Christina Kuhn
Susanne Kunze
Naim Shabani
Ansgar Brüning
Klaus Friese
Ioannis Mylonas
Publikationsdatum: 01.07.2011
Verlag: Springer-Verlag
Erschienen in: Archives of Gynecology and Obstetrics / Ausgabe 1/2011
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-010-1614-y

Neu im Fachgebiet Gynäkologie und Geburtshilfe

17.04.2024 | Postoperative nausea and vomiting | Nachrichten

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Inhibin/activin-betaC subunit does not represent a prognostic parameter in human endometrial cancer

Abstract

Introduction

Materials and methods

Results

Conclusion

Neu im Fachgebiet Gynäkologie und Geburtshilfe

Hochrisiko-Eingriffe für postoperative Übelkeit

Adjuvante Brustkrebstherapie: Doppelt hält besser

Manche Gestagene können das Risiko für Meningeome erhöhen

Stillende Frauen haben geringeres kardiovaskuläres Risiko

Update Gynäkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Introduction

Materials and methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2011

A randomized controlled study investigating the necessity of routine cervical dilatation during elective cesarean section

The association with age, human tissue kallikreins 6 and 10 and hemostatic markers for survival outcome from epithelial ovarian cancer

HIV-infection and modern antiretroviral therapy impair sperm quality

Antenatal three-dimensional sonographic features of Roberts syndrome

Pregnancy outcome in women with autoimmune hepatitis

Self-reported oral hygiene habits and periodontal symptoms among postpartum women

Neu im Fachgebiet Gynäkologie und Geburtshilfe

Hochrisiko-Eingriffe für postoperative Übelkeit

Adjuvante Brustkrebstherapie: Doppelt hält besser

Manche Gestagene können das Risiko für Meningeome erhöhen

Stillende Frauen haben geringeres kardiovaskuläres Risiko

Update Gynäkologie