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01-10-2013 | Original Article

TROP2 expression and its correlation with tumor proliferation and angiogenesis in human gliomas

Authors: Shanglei Ning, Nan Liang, Bin Liu, Xin Chen, Qi Pang, Tao Xin

Published in: Neurological Sciences | Issue 10/2013

Abstract

Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein which is associated with tumor development and progression in a variety of epithelial carcinomas, while its expression and role in gliomas have not been considered. The aim of the study was to investigate TROP2 expression in malignant gliomas with different World Health Organization (WHO) classification and its correlation with tumor proliferation and angiogenesis. Immuohistochemistry was used to determine TROP2 and Ki-67 expression and microvessel density (MVD) in tumor specimens and normal brain tissues from 69 glioma patients and the relationship between TROP2 and Ki-67 and MVD was investigated. Immunohistochemistry results showed that the TROP2 expression was found in 59 (85.5 %) of the 69 tumor specimens, but no expression in normal brain tissues. Furthermore, TROP2 expression is significantly higher in WHO grade III (P = 0.025) and WHO grade IV (P = 0.011) gliomas than in WHO grade II gliomas. TROP2 expression correlates with Ki-67 (r = 0.676, P = 0.012) and MVD (r = 0.365, P = 0.035), but not with gender or age in human gliomas. These results suggested that the TROP2 correlated with malignancy, proliferation and angiogenesis in human gliomas. This is the first study describing TROP2 expression in gliomas and its proliferation and angiogenesis-related characteristic may serve as a potential therapeutic target for glioma treatment.

Vredenburgh JJ, Desjardins A, Reardon DA, Friedman HS (2009) Experience with irinotecan for the treatment of malignant glioma. Neuro Oncol 11:80–91PubMedCrossRef

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109PubMedCrossRef

Meyer MA (2008) Malignant gliomas in adults. N Engl J Med 359:1850PubMed

Germano IM, Binello E (2009) Gene therapy as an adjuvant treatment for malignant gliomas: from bench to bedside. J Neurooncol 93:79–87PubMedCrossRef

Lipinski M, Parks DR, Rouse RV, Herzenberg LA (1981) Human trophoblast cell-surface antigens defined by monoclonal antibodies. Proc Natl Acad Sci USA 78:5147–5150PubMedCrossRef

Cubas R, Li M, Chen C, Yao Q (2009) Trop2: a possible therapeutic target for late stage epithelial carcinomas. Biochim Biophys Acta 1796:309–314PubMed

Mühlmann G, Spizzo G, Gostner J, Zitt M, Maier H, Moser P, Gastl G, Zitt M, Müller HM, Margreiter R, Ofner D, Fong D (2009) TROP2 expression as prognostic marker for gastric carcinoma. J Clin Pathol 62:152–158PubMedCrossRef

Fong D, Moser P, Krammel C, Gostner JM, Margreiter R, Mitterer M, Gastl G, Spizzo G (2008) High expression of TROP2 correlates with poor prognosis in pancreatic cancer. Br J Cancer 99:1290–1295PubMedCrossRef

Ohmachi T, Tanaka F, Mimori K, Inoue H, Yanaga K, Mori M (2006) Clinical significance of TROP2 expression in colorectal cancer. Clin Cancer Res 12:3057–3063PubMedCrossRef

10.

Wang J, Day R, Dong Y, Weintraub SJ, Michel L (2008) Identification of Trop-2 as an oncogene and an attractive therapeutic target in colon cancers. Mol Cancer Ther 7:280–285PubMedCrossRef

11.

Fong D, Spizzo G, Gostner JM, Gastl G, Moser P, Krammel C, Gerhard S, Rasse M, Laimer K (2008) TROP2: a novel prognostic marker in squamous cell carcinoma of the oral cavity. Mod Pathol 21:186–191PubMed

12.

Cubas R, Zhang S, Li M, Chen C, Yao Q (2010) Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway. Mol Cancer 9:253PubMedCrossRef

13.

Trerotola M, Cantanelli P, Guerra E, Tripaldi R, Aloisi AL, Bonasera V, Lattanzio R, Lange RD, Weidle UH, Piantelli M, Alberti S (2012) Upregulation of Trop-2 quantitatively stimulates human cancer growth. Oncogene. doi:10.1038/onc.2012.36

14.

Mosolits S, Markovic K, Frodin JE, Virving L, Magnusson CG, Steinitz M, Fagerberg J, Mellstedt H (2004) Vaccination with Ep-CAM protein or anti-idiotypic antibody induces Th1-biased response against MHC class I- and II-restricted Ep-CAM epitopes in colorectal carcinoma patients. Clin Cancer Res 10:5391–5402PubMedCrossRef

15.

Raji R, Guzzo F, Carrara L, Varughese J, Cocco E, Bellone S, Betti M, Todeschini P, Gasparrini S, Ratner E, Silasi DA, Azodi M, Schwartz P, Rutherford TJ, Buza N, Pecorelli S, Santin AD (2011) Uterine and ovarian carcinosarcomas overexpressing Trop-2 are sensitive to hRS7, a humanized anti-Trop-2 antibody. J Exp Clin Cancer Res 30:106PubMedCrossRef

16.

Varughese J, Cocco E, Bellone S, de Leon M, Bellone M, Todeschini P, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD (2011) Uterine serous papillary carcinomas overexpress human trophoblast-cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized anti-Trop-2 monoclonal antibody. Cancer 117:3163–3172PubMedCrossRef

17.

Govindan SV, Stein R, Qu Z, Chen S, Andrews P, Ma H, Hansen HJ, Griffiths GL, Horak ID, Goldenberg DM (2004) Preclinical therapy of breast cancer with a radioiodinated humanized anti-EGP-1 monoclonal antibody: advantage of a residualizing iodine radiolabel. Breast Cancer Rea Treat 84:173–182CrossRef

18.

Cea V, Sala C, Verpelli C (2012) Antiangiogenic therapy for glioma. J Signal Transduct 2012:483040PubMed

19.

Ralte AM, Sharma MC, Karak AK, Mehta VS, Sarkar C (2001) Clinicopathological features, MIB-1 labeling index and apoptotic index in recurrent astrocytic tumors. Pathol Oncol Res 7:267–278PubMedCrossRef

20.

Johannessen AL, Torp SH (2006) The clinical value of Ki-67/MIB-1 labeling index in human astrocytomas. Pathol Oncol Res 12:143–147PubMedCrossRef

21.

Preusser M, Heinzl H, Gelpi E, Schonegger K, Haberler C, Birner P, Marosi C, Hegi M, Gorlia T, Hainfellner JA (2006) Histopathologic assessment of hot-spot microvessel density and vascular patterns in glioblastoma: poor observer agreement limits clinical utility as prognostic factors: a translational research project of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Cancer 107:162–170PubMedCrossRef

22.

Rahmah NN, Sakai K, Sano K, Hongo K (2012) Expression of RECK in endothelial cells of glioma: comparison with CD34 and VEGF expressions. J Neurooncol 107:559–564PubMedCrossRef

23.

Pang B, Fan H, Zhang IY, Liu B, Feng B, Meng L, Zhang R, Sadeghi S, Guo H, Pang Q (2012) HMGA1 expression in human gliomas and its correlation with tumor proliferation, invasion and angiogenesis. J Neurooncol 106:543–549PubMedCrossRef

24.

Goldstein AS, Stoyanova T, Witte ON (2010) Primitive origins of prostate cancer: in vivo evidence for prostate-regenerating cells and prostate cancer-initiating cells. Mol Oncol 4:385–396PubMedCrossRef

25.

Ben-Neriah Y, Karin M (2011) Inflammation meets cancer, with NF- κB as the matchmaker. Nat Immunol 12:715–723PubMedCrossRef

26.

Guerra E, Trerotola M, Dell’ Arciprete R, Bonasera V, Palombo B, El-Sewedy T, Ciccimarra T, Crescenzi C, Lorenzini F, Rossi C, Vacca G, Lattanzio R, Piantelli M, Alberti S (2008) A bicistronic CYCLIN D1-TROP2 mRNA chimera demonstrates a novel oncogenic mechanism in human cancer. Cancer Res 68:8113–8121PubMedCrossRef

27.

Stoyanova T, Goldstein AS, Cai H, Drake JM, Huang J, Witte ON (2012) Regulated proteolysis of Trop2 drives epithelial hyperplasia and stem cell self-renewal via beta-catenin signaling. Genes Dev 26:2271–2285PubMedCrossRef

28.

Bello L, Giussani C, Carrabba G, Pluderi M, Costa F, Bikfalvi A (2004) Angiogenesis and invasion in gliomas. Cancer Treat Res 117:263–284PubMedCrossRef

29.

Leon SP, Folkerth RD, Black PM (1996) Microvessel density is a prognostic indicator for patients with astroglial brain tumors. Cancer 77:362–372PubMedCrossRef

30.

Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676PubMedCrossRef

31.

Ellis LM (2004) Epidermal growth factor receptor in tumor angiogenesis. Hematol Oncol Clin North Am 18:1007–1021PubMedCrossRef

32.

Guo P, Hu B, Gu W, Xu L, Wang D, Huang HJ, Cavenee WK, Cheng SY (2003) Platelet-derived growth factor-B enhances glioma angiogenesis by stimulating vascular endothelial growth factor expression in tumor endothelia and by promoting pericyte recruitment. Am J Pathol 162:1083–1093PubMedCrossRef

33.

Chamberlain MC (2011) Bevacizumab for the treatment of recurrent glioblastoma. Clin Med Insights Oncol 5:117–129PubMedCrossRef

34.

Shan YF, Huang YL, Xie YK, Tan YH, Chen BC, Zhou MT, Shi HQ, Yu ZP, Song QT, Zhang QY (2011) Angiogenesis and clinicopathologic characteristics in different hepatocellular carcinoma subtypes defined by EpCAM and alpha-fetoprotein expression status. Med Oncol 28:1012–1016PubMedCrossRef

35.

Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Goldenberg DM (2011) Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: preclinical studies in human cancer xenograft models and monkeys. Clin Cancer Res 17:3157–3169PubMedCrossRef

Title: TROP2 expression and its correlation with tumor proliferation and angiogenesis in human gliomas
Authors: Shanglei Ning
Nan Liang
Bin Liu
Xin Chen
Qi Pang
Tao Xin
Publication date: 01-10-2013
Publisher: Springer Milan
Published in: Neurological Sciences / Issue 10/2013
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-013-1326-8

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TROP2 expression and its correlation with tumor proliferation and angiogenesis in human gliomas

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