Glycodelin A is a prognostic marker to predict poor outcome in advanced stage ovarian cancer patients

BMC Research Notes

Udo Jeschke²  Doris Mayr⁴  Klaus Friese³  Miriam Lenhard³  Sabine Heublein²  Christoph Scholz¹ 

[1] Department of Obstetrics and Gynecology, Heinrich-Heine University, Düsseldorf, Germany;Department of Obstetrics and Gynecology, Campus Innenstadt, Ludwig-Maximilians-University Munich, Munich, 80337, Germany;Department of Obstetrics and Gynecology, Campus Großhadern, Ludwig-Maximilians-University Munich, Munich, 80337, Germany;Department of Pathology, Ludwig-Maximilians-University Munich, Munich, 80337, Germany

关键词: Prognosis;    Immunohistochemistry;    Glycodelin;    Ovarian cancer;   

Others  :  1165517
DOI  :  10.1186/1756-0500-5-551

 received in 2012-06-26, accepted in 2012-09-22,  发布年份 2012

【 摘 要 】

Background

Glycodelin is a cell surface glycoprotein offering a unique gender specific carbohydrate configuration. Sialylated carbohydrate structures, which are unusual for mammals, characterize Glycodelin isolated from amniotic fluid (Glycodelin A, GdA). Glycodelin in general exerts multiple, partly opposing functions ranging from immunosuppression to cell differentiation. As these markedly influence tumorigenesis, this study aimed to clarify whether expression of different Glycodelin isoforms is related to clinicopathological characteristics and prognosis of ovarian cancer patients. Further the use of Glycodelin as a serum marker in benign and malignant ovarian diseases was evaluated.

Methods

Ovarian cancer specimens (n = 152) were stained for Glycodelin with carbohydrate and peptide specific antibodies. Associations between Glycodelin expression and histological grading, FIGO stage as well as patient’s prognosis were examined. Glycodelin was correlated to expression of gonadotropin receptors and mucin-1, which are discussed as ovarian cancer tissue markers. In addition, Glycodelin serum concentrations were analyzed in patients suffering from benign (n = 73) or malignant (n = 38) ovarian neoplasias.

Results

Glycodelin A was found to be an independent prognostic marker for poor prognosis in advanced ovarian cancer patients. GdA staining correlated with gonadotropin receptor (FSHR and LHCGR) and with hCG expression. Gd expression showed a positive correlation with a tumour-associated epitope of mucin 1 (TA-MUC1). Further, compared to ovarian cancer, serum Gd was increased in patients with benign ovarian tumors.

Conclusion

Glycodelin A might be related to tumor aggressiveness and poor clinical outcome in advanced epithelial ovarian cancer. Glycodelin serum levels found in patients suffering from benign ovarian tumors, might contribute to a more global attenuation during progression of these precursor lesions.

【 授权许可】

   
2012 Scholz et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Classe JM, Jaffre I, Frenel JS, Bordes V, Dejode M, Dravet F, Ferron G, Marchal F, Berton Rigaud D, Loussouarn D: Prognostic factors for patients treated for a recurrent FIGO stage III ovarian cancer: a retrospective study of 108 cases. Eur J Surg Oncol 2011, 37(11):971-977.
• [2]Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ: Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 2002, 20(5):1248-1259.
• [3]Lenhard SM, Bufe A, Kumper C, Stieber P, Mayr D, Hertlein L, Kirschenhofer A, Friese K, Burges A: Relapse and survival in early-stage ovarian cancer. Arch Gynecol Obstet 2009, 280(1):71-77.
• [4]Lee CL, Lam KK, Koistinen H, Seppala M, Kurpisz M, Fernandez N, Pang RT, Yeung WS, Chiu PC: Glycodelin-A as a paracrine regulator in early pregnancy. J Reprod Immunol 2011, 90(1):29-34.
• [5]Ren S, Liu S, Howell PM Jr, Zhang G, Pannell L, Samant R, Shevde-Samant L, Tucker JA, Fodstad O, Riker AI: Functional characterization of the progestagen-associated endometrial protein gene in human melanoma. J Cell Mol Med 2010, 14(6B):1432-1442.
• [6]Scholz C, Toth B, Brunnhuber R, Rampf E, Weissenbacher T, Santoso L, Friese K, Jeschke U: Glycodelin A induces a tolerogenic phenotype in monocyte-derived dendritic cells in vitro. Am J Reprod Immunol 2008, 60(6):501-512.
• [7]Jeschke U, Toth B, Scholz C, Friese K, Makrigiannakis A: Glycoprotein and carbohydrate binding protein expression in the placenta in early pregnancy loss. J Reprod Immunol 2010, 85(1):99-105.
• [8]Scholl B, Bersinger NA, Kuhn A, Mueller MD: Correlation between symptoms of pain and peritoneal fluid inflammatory cytokine concentrations in endometriosis. Gynecol Endocrinol 2009, 25(11):701-706.
• [9]Bersinger NA, Birkhauser MH, Yared M, Wunder DM: Serum glycodelin pattern during the menstrual cycle in healthy young women. Acta Obstet Gynecol Scand 2009, 88(11):1215-1221.
• [10]Koistinen H, Hautala LC, Seppala M, Stenman UH, Laakkonen P, Koistinen R: The role of glycodelin in cell differentiation and tumor growth. Scand J Clin Lab Invest 2009, 69(4):452-459.
• [11]Scholz C, Rampf E, Toth B, Brunnhuber R, Weissenbacher T, Friese K, Jeschke U: Ovarian cancer-derived glycodelin impairs in vitro dendritic cell maturation. J Immunother 2009, 32(5):492-497.
• [12]Bohn H, Kraus W, Winckler W: New soluble placental tissue proteins: their isolation, characterization, localization and quantification. Placenta Suppl 1982, 4:67-81.
• [13]Koistinen H, Koistinen R, Dell A, Morris HR, Easton RL, Patankar MS, Oehninger S, Clark GF, Seppala M: Glycodelin from seminal plasma is a differentially glycosylated form of contraceptive glycodelin-A. Mol Hum Reprod 1996, 2(10):759-765.
• [14]Jeschke U, Bischof A, Speer R, Briese V, Richter DU, Bergemann C, Mylonas I, Shabani N, Friese K, Karsten U: Development of monoclonal and polyclonal antibodies and an ELISA for the determination of glycodelin in human serum, amniotic fluid and cystic fluid of benign and malignant ovarian tumors. Anticancer Res 2005, 25(3A):1581-1589.
• [15]Jeschke U, Kuhn C, Mylonas I, Schulze S, Friese K, Mayr D, Speer R, Briese V, Richter DU, Haase M: Development and characterization of monoclonal antibodies for the immunohistochemical detection of glycodelin A in decidual, endometrial and gynaecological tumour tissues. Histopathology 2006, 48(4):394-406.
• [16]Remmele W, Stegner HE: [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue]. Pathologe 1987, 8(3):138-140.
• [17]Lenhard M, Lennerova T, Ditsch N, Kahlert S, Friese K, Mayr D, Jeschke U: Opposed roles of follicle-stimulating hormone and luteinizing hormone receptors in ovarian cancer survival. Histopathology 2011, 58(6):990-994.
• [18]Lenhard M, Tsvilina A, Schumacher L, Kupka M, Ditsch N, Mayr D, Friese K, Jeschke U: Human chorionic gonadotropin and its relation to grade, stage and patient survival in ovarian cancer. BMC Cancer 2012, 12(1):2. BioMed Central Full Text
• [19]Hautala LC, Greco D, Koistinen R, Heikkinen T, Heikkila P, Aittomaki K, Blomqvist C, Koistinen H, Nevanlinna H: Glycodelin expression associates with differential tumour phenotype and outcome in sporadic and familial non-BRCA1/2 breast cancer patients. Breast Cancer Res Treat 2011, 128(1):85-95.
• [20]Kunert-Keil C, Steinmuller F, Jeschke U, Gredes T, Gedrange T: Immunolocalization of glycodelin in human adenocarcinoma of the lung, squamous cell carcinoma of the lung and lung metastases of colonic adenocarcinoma. Acta Histochem 2011, 113(8):798-802.
• [21]Mandelin E, Lassus H, Seppala M, Leminen A, Gustafsson JA, Cheng G, Butzow R, Koistinen R: Glycodelin in ovarian serous carcinoma: association with differentiation and survival. Cancer Res 2003, 63(19):6258-6264.
• [22]Dell A, Morris HR, Easton RL, Panico M, Patankar M, Oehniger S, Koistinen R, Koistinen H, Seppala M, Clark GF: Structural analysis of the oligosaccharides derived from glycodelin, a human glycoprotein with potent immunosuppressive and contraceptive activities. J Biol Chem 1995, 270(41):24116-24126.
• [23]Jeschke U, Mylonas I, Kunert-Keil C, Stahn R, Scholz C, Janni W, Kuhn C, Schroder E, Mayr D, Friese K: Immunohistochemistry, glycosylation and immunosuppression of glycodelin in human ovarian cancer. Histochem Cell Biol 2009, 131(2):283-295.
• [24]Napoletano C, Bellati F, Landi R, Pauselli S, Marchetti C, Visconti V, Sale P, Liberati M, Rughetti A, Frati L: Ovarian cancer cytoreduction induces changes in T cell population subsets reducing immunosuppression. J Cell Mol Med 2010, 14(12):2748-2759.
• [25]Zheng W, Lu JJ, Luo F, Zheng Y, Feng Y, Felix JC, Lauchlan SC, Pike MC: Ovarian epithelial tumor growth promotion by follicle-stimulating hormone and inhibition of the effect by luteinizing hormone. Gynecol Oncol 2000, 76(1):80-88.
• [26]Minegishi T, Kameda T, Hirakawa T, Abe K, Tano M, Ibuki Y: Expression of gonadotropin and activin receptor messenger ribonucleic acid in human ovarian epithelial neoplasms. Clin Cancer Res 2000, 6(7):2764-2770.
• [27]Toth B, Roth K, Kunert-Keil C, Scholz C, Schulze S, Mylonas I, Friese K, Jeschke U: Glycodelin protein and mRNA is downregulated in human first trimester abortion and partially upregulated in mole pregnancy. J Histochem Cytochem 2008, 56(5):477-485.
• [28]Jeschke U, Karsten U, Reimer T, Richter DU, Bergemann C, Briese V, Mylonas I, Friese K: Stimulation of hCG protein and mRNA in first trimester villous cytotrophoblast cells in vitro by glycodelin A. J Perinat Med 2005, 33(3):212-218.
• [29]Dian D, Janni W, Kuhn C, Mayr D, Karsten U, Mylonas I, Friese K, Jeschke U: Evaluation of a novel anti-mucin 1 (MUC1) antibody (PankoMab) as a potential diagnostic tool in human ductal breast cancer; comparison with two established antibodies. Onkologie 2009, 32(5):238-244.
• [30]Jaffe RC, Donnelly KM, Fazleabas AT: The induction of baboon glycodelin expression by progesterone is not through Sp1. Mol Hum Reprod 2003, 9(1):35-40.
• [31]Horowitz IR, Cho C, Song M, Flowers LC, Santanam N, Parthasarathy S, Ramachandran S: Increased glycodelin levels in gynecological malignancies. Int J Gynecol Cancer 2001, 11(3):173-179.
• [32]Richter C, Baetje M, Bischof A, Makovitzky J, Richter DU, Gerber B, Briese V: Expression of the glycodelin A gene and the detection of its protein in tissues and serum of ovarian carcinoma patients. Anticancer Res 2007, 27(4A):2023-2025.
• [33]Staebler A, Diebold J: [Molecular pathology of epithelial ovarian neoplasias: from the phenotype-genotype correlation to new targets in diagnostics and therapy]. Pathologe 2007, 28(3):180-186.
• [34]Lang EE, Venkatraman G: Glycodelin gene expression in human peripheral white blood cells. Ir J Med Sci 2007, 176(2):101-104.
• [35]Tulppala M, Julkunen M, Tiitinen A, Stenman UH, Seppala M: Habitual abortion is accompanied by low serum levels of placental protein 14 in the luteal phase of the fertile cycle. Fertil Steril 1995, 63(4):792-795.
• [36]Dalton CF, Laird SM, Estdale SE, Saravelos HG, Li TC: Endometrial protein PP14 and CA-125 in recurrent miscarriage patients; correlation with pregnancy outcome. Hum Reprod 1998, 13(11):3197-3202.
• [37]Loukovaara S, Immonen IR, Loukovaara MJ, Koistinen R, Kaaja RJ: Glycodelin: a novel serum anti-inflammatory marker in type 1 diabetic retinopathy during pregnancy. Acta Ophthalmol Scand 2007, 85(1):46-49.