Expression of Thromhospondin-1 in Gastric Cancer and Metastatic Lymph Node Tissues and Its Relationship to Tumor　Angiogenesis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CHEN Jing ¹ , ZHI Yu ² , CHANG Xiaojing ¹ , ZHU Xinjiang ¹ ,  DAI Dongqiu ¹

1.Department of Gastrointestinal Surgery， The Fourth Affiliated Hospital， China Medical University， Shenyang 110032， Liaoning Province， China;;
2.Department of Colon and Rectum， Affiliated Xinhua Hospital， Dalian University， Dalian 116021， Liaoning Province， China;

Corresponding author：

DAI Dongqiu, Email: daidq63@163.com

Keywords：

Thromhospondin-1; Vascular endothelial growth factor; Microvessel density; Gastric cancer

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Objective 　To detect the expression of thromhospondin-1 （TSP-1） in gastric cancer and metastatic
lymph node tissues， and to study its relationship of TSP-1 to clinicopathologic parameters or tumor angiogenesis.
Methods 　The TSP-1 and vascular endothelial growth factor （VEGF） expressions and microvessel density （MVD） were evaluated by immunohistochemistry in 72 specimens obtained by gastric resection from patients with gastric cancer， including corres-ponding adjacent normal gastric mucosa tissues （distant from cancer ≥5 cm） and lymph nodes surrounding cancer. A semiquantitative scoring system was used for evaluating the staining. The relationship of TSP-1 to VEGF expression， MVD， or clinicopathologic parameters was analyzed.
Results 　① TSP-1 positive expression rate was 45.8% （33/72） in the primary gastric cancer tissues， 90.3% （65/72） in the corresponding adjacent normal gastric mucosa tissues， and 50.8% （30/59） in the metastatic lymph nodes tissues. The expressions of TSP-1 in the primary gastric cancer tissues and metastatic lymph nodes tissues were significantly lower than those in the adjacent normal gastric mucosa tissues （χ2=32.710，P=0.000；χ2=25.298， P=0.000）. The expression of TSP-1 had no statistical significance in the primary gastric cancer tissues as compared with in the metastatic lymph nodes tissues （χ2=0.327， P=0.568）. ② The expression of TSP-1 in the metastatic lymph nodes tissues was significantly lower than that in the non-metastatic lymph nodes tissues （Z=-2.573， P=0.010）. ③The expression of TSP-1 in the primary gastric cancer tissues and metastatic lymph nodes tissues suggested a negative correlation with VEGF （rs=-0.309， P=0.008；rs=-0.269， P=0.040） and MVD （rs=-0.348， P=0.003；rs=-0.272， P=0.037）.
Conclusions 　TSP-1 expression is down-regulated and has a negative correlation with VEGF and MVD in the primary gastric cancer and the metastatic lymph nodes tissues. According to the present results， it seems likely that TSP-1 is a tumor angiogenesis inhibitor.

Citation： CHEN Jing,ZHI Yu,CHANG Xiaojing,ZHU Xinjiang,DAI Dongqiu. Expression of Thromhospondin-1 in Gastric Cancer and Metastatic Lymph Node Tissues and Its Relationship to Tumor　Angiogenesis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(11): 1267-1262. doi: Copy

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26.	Marx AH， Tharun L， Muth J， et al. HER-2 amplification is highlyhomogenous in gastric cancer[J]. Hum Pathol， 2009， 40(6)：769-777.
27.	Negri FV， Bozzetti C， Ardizzoni A， et al. HER-2 discordance between primary gastric carcinoma and paired lymph node metastasis[J]. Hum Pathol， 2011， 42(6)：909-910.
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31.	(3)：329-334.
32.	.

1. Yang L. Incidence and mortality of gastric cancer in China[J]. World J Gastroenterol， 2006， 12(1)：17-20.
2. Wang YD， Wu P， Mao JD， et al. Relationship between vascular invasion and microvessel density and micrometastasis[J]. World J Gastroenterol， 2007， 13(46)：6269-6273.
3. Zerbini G， Lorenzi M， Palini A. Tumor angiogenesis[J]. Engl J Med， 2008， 359(7)：763-764. doi：10.1056/NEJMc081278.
4. Cook KM， Figg WD. Angiogenesis inhibitors：current strategies and future prospects[J]. CA Cancer J Clin， 2010， 60(4)：222-243.
5. Gadbail AR， Mankar Gadbail MP， Hande A， et al. Tumor angiogenesis：role in locally aggressive biological behavior of amelobla-stoma and keratocystic odontogenic tumor[J]. Head Neck， 2013，.
6. Lawler PR， Lawler J. Molecular basis for the regulation of angio-genesis by thrombospondin-1 and -2[J]. Cold Spring Harb Pers-pect Med， 2012， 2(5)：a006627. doi：10.1101/cshperspect. a00-.
7. Ribatti D. The crucial role of vascular permeability factor/vascular endothelial growth factor in angiogenesis：a historical review[J]. Br J Haematol， 2005， 128(3)：303-309.
8. Miyato H， Kitayama J， Ishigami H， et al. Loss of sympathetic nerve fibers around intratumoral arterioles reflects malignant potential of gastric cancer[J]. Ann Surg Oncol， 2011， 18(8)：2281-2288.
9. Iordache S， Saftoiu A， Georgescu CV， et al. Vascular endothe-lial growth factor expression and microvessel density—two usefultools for the assessment of prognosis and survival in gastric cancer patients[J]. J Gastrointestin Liver Dis， 2010， 19(2)：135-139.
10. Makrilia N， Lappa T， Xyla V， et al. The role of angiogenesis in solid tumours：an overview[J]. Eur J Intern Med， 2009， 20(7)：663-671.
11. Muhammadnejad S， Muhammadnejad A， Haddadi M， et al. Correlation of microvessel density with nuclear pleomorphism， mitotic count and vascular invasion in breast and prostate cancers at preclinical and clinical levels[J]. Asian Pac J Cancer Prev， 2013， 14(1)：63-68.
12. Nadkarni NJ， Geest KD， Neff T， et al. Microvessel density and p53 mutations in advanced-stage epithelial ovarian cancer[J]. Cancer Lett， 2013， 331(1)：99-104.
13. Jiménez B， Volpert OV， Crawford SE， et al. Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1[J]. Nat Med， 2000， 6(1)：41-48.
14. Fleitas T， Martinez-Sales V， Vila V， et al. VEGF and TSP1 levelscorrelate with prognosis in advanced non-small cell lung cancer. Clinical & translational oncology：official publication of the Fede-ration of Spanish Oncology Societies and of the National Cancer Institute of Mexico， 2013. doi：10.1007/s12094-013-1020-6.
15. Armstrong LC， Bornstein P. Thrombospondins 1 and 2 function as inhibitors of angiogenesis[J]. Matrix Biol， 2003， 22(1)：63-71.
16. Parkin DM， Bray F， Ferlay J， et al. Global cancer statistics， 2002[J]. CA Cancer J Clin， 2005， 55(2)：74-108.
17. Fontana A， Filleur S， Guglielmi J， et al. Human breast tumors override the antiangiogenic effect of stromal thrombospondin-1 in vivo[J]. Int J Cancer， 2005， 116(5)：686-691.
18. Firlej V， Mathieu JR， Gilbert C， et al. Thrombospondin-1 triggerscell migration and development of advanced prostate tumors[J]. Cancer Res， 2011， 71(24)：7649-7658.
19. Nakao T， Kurita N， Komatsu M， et al. Expression of thrombos-pondin-1 and Ski are prognostic factors in advanced gastric cancer[J]. Int J Clin Oncol， 2011， 16(2)：145-152.
20. 文卫，杨连粤，黄耿文，等. TSP-1和VEGF在肝细胞癌新生血管生成中的作用[J]. 中华肝胆外科杂志， 2005， 11(1)：17-19.
21. Jiang M， Mou CZ， Han T， et al. Thrombospondin-1 and transforming growth factor-β1 levels in prolactinoma and their clinical significance[J]. J Int Med Res， 2012， 40(4)：1284-1294.
22. 王蓓，吕成余，谢洪虎. 351例胃癌术后患者的预后因素分析[J]. 中国普外基础与临床杂志， 2012， 19(7)：743-748.
23. Zhang J， Ito R， Oue N， et al. Expression of thrombospondin-1 is correlated with microvessel density in gastric carcinoma[J]. Virchows Arch， 2003， 442(6)：563-568.
24. Hippo Y， Yashiro M， Ishii M， et al. Differential gene expression profiles of scirrhous gastric cancer cells with high metastatic potential to peritoneum or lymph nodes[J]. Cancer Res， 2001， 61(3)：889-895.
25. Bilous M， Osamura RY， Rüschoff J， et al. HER-2 amplification is highly homogenous in gastric cancer[J]. Hum Pathol， 2010， 41(2)：304-306.
26. Marx AH， Tharun L， Muth J， et al. HER-2 amplification is highlyhomogenous in gastric cancer[J]. Hum Pathol， 2009， 40(6)：769-777.
27. Negri FV， Bozzetti C， Ardizzoni A， et al. HER-2 discordance between primary gastric carcinoma and paired lymph node metastasis[J]. Hum Pathol， 2011， 42(6)：909-910.
28. Zidan J， Dashkovsky I， Stayerman C， et al. Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease[J]. Br J Cancer， 2005， 93(5)：552-556.
29. Kim JH， Kim MA， Lee HS， et al. Comparative analysis of protein expressions in primary and metastatic gastric carcinomas[J]. Hum Pathol， 2009， 40(3)：314-322.
30. Byrne GJ， Hayden KE， McDowell G， et al. Angiogenic characteristics of circulating and tumoural thrombospondin-1 in breast cancer[J]. Int J Oncol， 2007， 31(5)：1127-1132.
31. (3)：329-334.
32. .

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of Thromhospondin-1 in Gastric Cancer and Metastatic Lymph Node Tissues and Its Relationship to Tumor　Angiogenesis

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Content

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of Thromhospondin-1 in Gastric Cancer and Metastatic Lymph Node Tissues and Its Relationship to Tumor Angiogenesis

Abstract Full text Figures/Tables Video References Cited by

Format

Content

Expression of Thromhospondin-1 in Gastric Cancer and Metastatic Lymph Node Tissues and Its Relationship to Tumor　Angiogenesis