Abstract
Angiogenesis plays a crucial role in tumor growth. Recently, endocan has emerged as a new marker of vascular endothelial cells from cancers in other organs. In this study, we elucidated the relationship between endocan expression and tumor invasion of pituitary adenoma. Tumor tissues were obtained from 70 patients with pituitary adenoma and were examined using fluorescence immunohistochemistry. Tissue samples included 4 adrenocorticotrophic hormone producing adenomas, 10 growth hormone-producing adenomas, 49 clinically nonfunctioning adenomas, 6 prolactin producing adenomas, and 1 thyroid-stimulating hormone producing adenoma. Endocan was exclusively expressed in CD34-positive vascular endothelial cells, with over 90 % colocalization. The CD34 expression was significantly elevated with endocan expression (linear regression slope, 1.200; r2 = 0.268, F = 23.08, p < 0.0001). As a percentage of CD34 expression, endocan expression was elevated in a Knosp grading dependent manner (Spearman’s r-value, 0.651; p < 0.0001), and was also significantly elevated in macroadenomas compared with microadenomas (p = 0.0133). However, no differences in endocan expression were observed between hormonal subtypes (p = 0.066; Kruskal–Wallis test), age (Spearman’s rank correlation test, p = 0.4909), or sex (Mann–Whitney test, p = 0.1701). These data show that endocan is closely related to tumor angiogenesis, and may predict tumor invasion into neighboring cavernous sinuses in pituitary adenomas.
Similar content being viewed by others
References
Di Ieva A, Grizzi F, Ceva-Grimaldi G, Aimar E, Serra S, Pisano P, Lorenzetti M, Tancioni F, Gaetani P, Crotti F, Tschabitscher M, Matula C, Rodriguez YBR (2010) The microvascular network of the pituitary gland: a model for the application of fractal geometry to the analysis of angioarchitecture and angiogenesis of brain tumors. J Neurosurg Sci 54:49–54
Di Ieva A, Weckman A, Di Michele J, Rotondo F, Grizzi F, Kovacs K, Cusimano MD (2013) Microvascular morphometrics of the hypophysis and pituitary tumors: from bench to operating theatre. Microvasc Res 89:7–14. doi:10.1016/j.mvr.2013.04.009
Jasek E, Furgal-Borzych A, Lis GJ, Litwin JA, Rzepecka-Wozniak E, Trela F (2009) Microvessel density and area in pituitary microadenomas. Endocr Pathol 20:221–226. doi:10.1007/s12022-009-9091-1
Lee JS, Park YS, Kwon JT, Nam TK, Lee TJ, Kim JK (2011) Radiological apoplexy and its correlation with acute clinical presentation, angiogenesis and tumor microvascular density in pituitary adenomas. J Korean Neurosurg Soc 50:281–287. doi:10.3340/jkns.2011.50.4.281
Zhang Y, He N, Zhou J, Chen Y (2011) The relationship between MRI invasive features and expression of EMMPRIN, galectin-3, and microvessel density in pituitary adenoma. Clin Imaging 35:165–173. doi:10.1016/j.clinimag.2010.06.002
Yamada S, Takada K (2003) Angiogenesis in pituitary adenomas. Microsc Res Tech 60:236–243. doi:10.1002/jemt.10262
Nomura R, Yoshida D, Teramoto A (2009) Stromal cell-derived factor-1 expression in pituitary adenoma tissues and upregulation in hypoxia. J Neurooncol 94:173–181. doi:10.1007/s11060-009-9835-2
Abid MR, Yi X, Yano K, Shih SC, Aird WC (2006) Vascular endocan is preferentially expressed in tumor endothelium. Microvasc Res 72:136–145. doi:10.1016/j.mvr.2006.05.010
Grigoriu BD, Depontieu F, Scherpereel A, Gourcerol D, Devos P, Ouatas T, Lafitte JJ, Copin MC, Tonnel AB, Lassalle P (2006) Endocan expression and relationship with survival in human non-small cell lung cancer. Clin Cancer Res Off J Am Assoc Cancer Res 12:4575–4582. doi:10.1158/1078-0432.ccr-06-0185
Sarrazin S, Adam E, Lyon M, Depontieu F, Motte V, Landolfi C, Lortat-Jacob H, Bechard D, Lassalle P, Delehedde M (2006) Endocan or endothelial cell specific molecule-1 (ESM-1): a potential novel endothelial cell marker and a new target for cancer therapy. Biochim Biophys Acta 1765:25–37. doi:10.1016/j.bbcan.2005.08.004
Scherpereel A, Depontieu F, Grigoriu B, Cavestri B, Tsicopoulos A, Gentina T, Jourdain M, Pugin J, Tonnel AB, Lassalle P (2006) Endocan, a new endothelial marker in human sepsis. Crit Care Med 34:532–537
Cornelius A, Cortet-Rudelli C, Assaker R, Kerdraon O, Gevaert MH, Prevot V, Lassalle P, Trouillas J, Delehedde M, Maurage CA (2012) Endothelial expression of endocan is strongly associated with tumor progression in pituitary adenoma. Brain Pathol 22:757–764. doi:10.1111/j.1750-3639.2012.00578.x
Filep JG (2006) Endocan or endothelial cell-specific molecule-1: a novel prognostic marker of sepsis? Crit Care Med 34:574–575
Maurage CA, Adam E, Mineo JF, Sarrazin S, Debunne M, Siminski RM, Baroncini M, Lassalle P, Blond S, Delehedde M (2009) Endocan expression and localization in human glioblastomas. J Neuropathol Exp Neurol 68:633–641. doi:10.1097/NEN.0b013e3181a52a7f
Rennel E, Mellberg S, Dimberg A, Petersson L, Botling J, Ameur A, Westholm JO, Komorowski J, Lassalle P, Cross MJ, Gerwins P (2007) Endocan is a VEGF-A and PI3 K regulated gene with increased expression in human renal cancer. Exp Cell Res 313:1285–1294. doi:10.1016/j.yexcr.2007.01.021
Zuo L, Zhang SM, Hu RL, Zhu HQ, Zhou Q, Gui SY, Wu Q, Wang Y (2008) Correlation between expression and differentiation of endocan in colorectal cancer. World J Gastroenterol WJG 14:4562–4568
Huang GW, Tao YM, Ding X (2009) Endocan expression correlated with poor survival in human hepatocellular carcinoma. Dig Dis Sci 54:389–394. doi:10.1007/s10620-008-0346-3
Hatfield KJ, Lassalle P, Leiva RA, Lindas R, Wendelboe O, Bruserud O (2011) Serum levels of endothelium-derived endocan are increased in patients with untreated acute myeloid leukemia. Hematology (Amsterdam, Netherlands) 16:351–356. doi:10.1179/102453311x13127324303434
Zhang S, Zuo L, Gui S, Zhou Q, Wei W, Wang Y (2012) Induction of cell differentiation and promotion of endocan gene expression in stomach cancer by melatonin. Mol Biol Rep 39:2843–2849. doi:10.1007/s11033-011-1043-4
El Behery MM, Seksaka MA, Ibrahiem MA, Saleh HS, El Alfy Y (2013) Clinicopathological correlation of endocan expression and survival in epithelial ovarian cancer. Arch Gynecol Obstet. doi:10.1007/s00404-013-2863-3
Mikkelsen ME, Shah CV, Scherpereel A, Lanken PN, Lassalle P, Bellamy SL, Localio AR, Albelda SM, Meyer NJ, Christie JD (2012) Lower serum endocan levels are associated with the development of acute lung injury after major trauma. J Crit Care 27(522):e511–e527. doi:10.1016/j.jcrc.2011.07.077
Zhang SM, Zuo L, Zhou Q, Gui SY, Shi R, Wu Q, Wei W, Wang Y (2012) Expression and distribution of endocan in human tissues. Biotechnic Histochem Off Publ Biol Stain Comm 87:172–178. doi:10.3109/10520295.2011.577754
Balta I, Balta S, Demirkol S, Mikhailidis DP, Celik T, Akhan M, Kurt O, Kurt YG, Aydin I, Kilic S (2013) Elevated serum levels of endocan in patients with psoriasis vulgaris: correlations with cardiovascular risk and activity of disease. Br J Dermatol. doi:10.1111/bjd.12525
De Freitas Caires N, Legendre B, Parmentier E, Scherpereel A, Tsicopoulos A, Mathieu D, Lassalle P (2013) Identification of a 14 kDa endocan fragment generated by cathepsin G, a novel circulating biomarker in patients with sepsis. J Pharm Biomed Anal 78–79:45–51. doi:10.1016/j.jpba.2013.01.035
Nault JC, Guyot E, Laguillier C, Chevret S, Ganne-Carrie N, N’Kontchou G, Beaugrand M, Seror O, Trinchet JC, Coelho J, Lassalle P, Charnaux N, Delehedde M, Sutton A, Nahon P (2013) Serum proteoglycans as prognostic biomarkers of hepatocellular carcinoma in patients with alcoholic cirrhosis. Cancer Epidemiol Biomark Prev. doi:10.1158/1055-9965.epi-13-0179
Roudnicky F, Poyet C, Wild P, Krampitz S, Negrini F, Huggenberger R, Rogler A, Stohr R, Hartmann A, Provenzano M, Otto VI, Detmar M (2013) Endocan is upregulated on tumor vessels in invasive bladder cancer where it mediates VEGF-A-induced angiogenesis. Cancer Res 73:1097–1106. doi:10.1158/0008-5472.can-12-1855
Pizarro CB, Oliveira MC, Pereira-Lima JF, Leaes CG, Kramer CK, Schuch T, Barbosa-Coutinho LM, Ferreira NP (2009) Evaluation of angiogenesis in 77 pituitary adenomas using endoglin as a marker. Neuropathology Off J Jpn Soc Neuropathol 29:40–44. doi:10.1111/j.1440-1789.2008.00937.x
Yoshida D, Nomura R, Teramoto A (2009) Signalling pathway mediated by CXCR7, an alternative chemokine receptor for stromal-cell derived factor-1alpha, in AtT20 mouse adrenocorticotrophic hormone-secreting pituitary adenoma cells. J Neuroendocrinol 21:481–488. doi:10.1111/j.1365-2826.2009.01867.x
Yoshida D, Koketshu K, Nomura R, Teramoto A (2010) The CXCR4 antagonist AMD3100 suppresses hypoxia-mediated growth hormone production in GH3 rat pituitary adenoma cells. J Neurooncol 100:51–64. doi:10.1007/s11060-010-0152-6
Viacava P, Gasperi M, Acerbi G, Manetti L, Cecconi E, Bonadio AG, Naccarato AG, Acerbi F, Parenti G, Lupi I, Genovesi M, Martino E (2003) Microvascular density and vascular endothelial growth factor expression in normal pituitary tissue and pituitary adenomas. J Endocrinol Invest 26:23–28
Acknowledgments
This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan (Nos. 20591726 and 18390405).
Conflict of interest
There are no conflicts of interest for all authors. Fumihiro Matano who is a member of the JNS have registered on-line Self-reported COI Disclosure Statement Forms through the web-site for JNS members.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Matano, F., Yoshida, D., Ishii, Y. et al. Endocan, a new invasion and angiogenesis marker of pituitary adenomas. J Neurooncol 117, 485–491 (2014). https://doi.org/10.1007/s11060-014-1377-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-014-1377-6