YKL-40 protein in osteosarcoma tumor tissue
Corresponding Author
Andrea Pohly Thorn
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, University of Copenhagen, Copenhagen, Denmark
Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Andrea Pohly Thorn, Department of Orthopedic Surgery U-2161, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. e-mail: [email protected]Search for more papers by this authorSøren Daugaard
Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorLise Hanne Christensen
Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorIb Jarle Christensen
Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorMichael Mørk Petersen
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorCorresponding Author
Andrea Pohly Thorn
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, University of Copenhagen, Copenhagen, Denmark
Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Andrea Pohly Thorn, Department of Orthopedic Surgery U-2161, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. e-mail: [email protected]Search for more papers by this authorSøren Daugaard
Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorLise Hanne Christensen
Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorIb Jarle Christensen
Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorMichael Mørk Petersen
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorAbstract
YKL-40, a cellular glycoprotein isolated from the human osteosarcoma (OS) cell line MG63, is increased in the blood of patients with various types of cancer, and is found as an independent prognostic variable for survival. YKL-40 is also present with variable intensity in the tumor cells of some cancer types, but survival results have been conflicting. The aim of this study was to investigate the tissue expression of YKL-40 and its possible role as a predictive marker in patients with OS. Forty-eight patients were included in the study. Diagnostic biopsies were analyzed by immunohistochemistry; YKL-staining scores as well as CD14 and CD163 scores were determined, and survival data were determined statistically. A universal intense immunostaining for YKL-40 was found in all tumor cells, but tumor cell/stroma ratio varied, and this ratio (%) served as staining score. Using 24% as mean score to divide the material, patients with tumors of high YKL-40 score had a better survival than patients with low score (p = 0.05). YKL-positive macrophages had no influence on the result. Unexpectedly and contrary to some other findings in cancer tissues, this study has shown a correlation between high YKL-40 tumor cell/matrix ratio and longer overall survival in OS.
References
- 1Ringsholt M, Hogdall EV, Johansen JS, Price PA, Christensen LH. YKL-40 protein expression in normal adult human tissues–an immunohistochemical study. J Mol Histol 2007; 38: 33–43.
- 2Johansen JS, Williamson MK, Rice JS, Price PA. Identification of proteins secreted by human osteoblastic cells in culture. J Bone Miner Res 1992; 7: 501–12.
- 3Aggerholm-Pedersen N, Maretty-Nielsen K, Keller J, Baerentzen S, Schroder H, Jorgensen PH, et al. The importance of standardized treatment in high-grade osteosarcoma: 30 years of experience from a hospital-based database. Acta Oncol 2014; 54: 1–8.
- 4Johansen JS, Hoyer PE, Larsen LA, Price PA, Mollgard K. YKL-40 protein expression in the early developing human musculoskeletal system. J Histochem Cytochem 2007; 55: 1213–28.
- 5Lee CG, Hartl D, Lee GR, Koller B, Matsuura H, Da Silva CA, et al. Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13-induced tissue responses and apoptosis. J Exp Med 2009; 206: 1149–66.
- 6Saidi A, Javerzat S, Bellahcene A, De Vos J, Bello L, Castronovo V, et al. Experimental anti-angiogenesis causes upregulation of genes associated with poor survival in glioblastoma. Int J Cancer 2008; 122: 2187–98.
- 7Shao R, Hamel K, Petersen L, Cao QJ, Arenas RB, Bigelow C, et al. YKL-40, a secreted glycoprotein, promotes tumor angiogenesis. Oncogene 2009; 28: 4456–68.
- 8Johansen JS. Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer. Dan Med Bull 2006; 53: 172–209.
- 9Shao R. YKL-40 acts as an angiogenic factor to promote tumor angiogenesis. Front Physiol 2013; 4: 122.
- 10Johansen JS, Jensen BV, Roslind A, Nielsen D, Price PA. Serum YKL-40, a new prognostic biomarker in cancer patients? Cancer Epidemiol Biomarkers Prev 2006; 15: 194–202.
- 11Tschirdewahn S, Reis H, Niedworok C, Nyirady P, Szendroi A, Schmid KW, et al. Prognostic effect of serum and tissue YKL-40 levels in bladder cancer. Urol Oncol 2014; 32: 663–9.
- 12Roslind A, Knoop AS, Jensen MB, Johansen JS, Nielsen DL, Price PA, et al. YKL-40 protein expression is not a prognostic marker in patients with primary breast cancer. Breast Cancer Res Treat 2008; 112: 275–85.
- 13Hogdall EV, Ringsholt M, Hogdall CK, Christensen IJ, Johansen JS, Kjaer SK, et al. YKL-40 tissue expression and plasma levels in patients with ovarian cancer. BMC Cancer 2009; 9: 8.
- 14Stawerski P, Wagrowska-Danilewicz M, Stasikowska-Kanicka O, Danilewicz M. Increased tissue immunoexpression of YKL-40 protein in high grade serous ovarian cancers. Pathol Res Pract 2011; 207: 573–6.
- 15Xiao XQ, Hassanein T, Li QF, Liu W, Zheng YH, Chen J. YKL-40 expression in human hepatocellular carcinoma: a potential biomarker? Hepatobiliary Pancreat Dis Int 2011; 10: 605–10.
- 16Wang D, Zhai B, Hu F, Liu C, Zhao J, Xu J. High YKL-40 serum concentration is correlated with prognosis of Chinese patients with breast cancer. PLoS ONE 2012; 7: e51127.
- 17Kang EJ, Jung H, Woo OH, Park KH, Woo SU, Yang DS, et al. YKL-40 expression could be a poor prognostic marker in the breast cancer tissue. Tumour Biol 2014; 35: 277–86.
- 18Bi J, Lau SH, Lv ZL, Xie D, Li W, Lai YR, et al. Overexpression of YKL-40 is an independent prognostic marker in gastric cancer. Hum Pathol 2009; 40: 1790–7.
- 19Pelloski CE, Mahajan A, Maor M, Chang EL, Woo S, Gilbert M, et al. YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma. Clin Cancer Res 2005; 11: 3326–34.
- 20Yang GF, Cai PY, Li XM, Deng HX, He WP, Xie D. Expression and clinical significance of YKL-40 protein in epithelial ovarian cancer tissues. Ai Zheng 2009; 28: 142–5.
- 21Daugaard S, Christensen LH, Hogdall E. Markers aiding the diagnosis of chondroid tumors: an immunohistochemical study including osteonectin, bcl-2, cox-2, actin, calponin, D2-40 (podoplanin), mdm-2, CD117 (c-kit), and YKL-40. APMIS 2009; 117: 518–25.
- 22Harving ML, Christensen LH, Ringsholt M, Lausten GS, Petersen MM. YKL-40 expression in soft-tissue sarcomas and atypical lipomatous tumors. An immunohistochemical study of 49 tumors. Acta Orthop 2014; 85: 195–200.
- 23Skaland I, Nordhus M, Gudlaugsson E, Klos J, Kjellevold KH, Janssen EA, et al. Evaluation of 5 different labeled polymer immunohistochemical detection systems. Appl Immunohistochem Mol Morphol 2010; 18: 90–6.
- 24Bramer JA, van Linge JH, Grimer RJ, Scholten RJ. Prognostic factors in localized extremity osteosarcoma: a systematic review. Eur J Surg Oncol 2009; 35: 1030–6.
- 25Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2002; 20: 776–90.
- 26Buddingh EP, Kuijjer ML, Duim RA, Burger H, Agelopoulos K, Myklebost O, et al. Tumor-infiltrating macrophages are associated with metastasis suppression in high-grade osteosarcoma: a rationale for treatment with macrophage activating agents. Clin Cancer Res 2011; 17: 2110–9.
- 27Iwata S, Ishii T, Kawai A, Hiruma T, Yonemoto T, Kamoda H, et al. Prognostic factors in elderly osteosarcoma patients: a multi-institutional retrospective study of 86 cases. Ann Surg Oncol 2014; 21: 263–8.
- 28Min D, Lin F, Shen Z, Zheng S, Tan L, Yu W, et al. Analysis of prognostic factors in 333 Chinese patients with high-grade osteosarcoma treated by multidisciplinary combined therapy. Asia Pac J Clin Oncol 2013; 9: 71–9.
- 29Pakos EE, Nearchou AD, Grimer RJ, Koumoullis HD, Abudu A, Bramer JA, et al. Prognostic factors and outcomes for osteosarcoma: an international collaboration. Eur J Cancer 2009; 45: 2367–75.
- 30Durnali A, Alkis N, Cangur S, Yukruk FA, Inal A, Tokluoglu S, et al. Prognostic factors for teenage and adult patients with high-grade osteosarcoma: an analysis of 240 patients. Med Oncol 2013; 30: 624.
- 31Damron TA, Ward WG, Stewart A. Osteosarcoma, chondrosarcoma, and Ewing's sarcoma: National Cancer Data Base Report. Clin Orthop Relat Res 2007; 459: 40–7.
- 32Wilkins RM, Cullen JW, Camozzi AB, Jamroz BA, Odom L. Improved survival in primary nonmetastatic pediatric osteosarcoma of the extremity. Clin Orthop Relat Res 2005; 438: 128–36.
- 33Yamamoto N, Tsuchiya H. Chemotherapy for osteosarcoma - where does it come from? What is it? Where is it going? Expert Opin Pharmacother 2013; 14: 2183–93.
- 34Schwab JH, Springfield DS, Raskin KA, Mankin HJ, Hornicek FJ. What's new in primary bone tumors. J Bone Joint Surg Am 2012; 94: 1913–9.
- 35Johansen JS, Lottenburger T, Nielsen HJ, Jensen JE, Svendsen MN, Kollerup G, et al. Diurnal, weekly, and long-time variation in serum concentrations of YKL-40 in healthy subjects. Cancer Epidemiol Biomarkers Prev 2008; 17: 2603–8.
