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Erschienen in: Medical Oncology 2/2013

01.06.2013 | Original Paper

Angiopoietin-2 expression is correlated with angiogenesis and overall survival in oral squamous cell carcinoma

verfasst von: Chao Li, Chang-jin Sun, Jin-chuan Fan, Ning Geng, Chun-hua Li, Jian Liao, Kun Mi, Gui-quan Zhu, Hong Ma, Yu-feng Song, Ya-ling Tang, Yu Chen

Erschienen in: Medical Oncology | Ausgabe 2/2013

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Abstract

This study sought to determine the expression of angiopoietin-2 (Ang-2) and vascular endothelial cell growth factor (VEGF) in oral squamous cell carcinoma (OSCC) and assess their correlations with tumor progression, angiogenesis, vessel maturation, and clinical survival. Tumor tissue from 102 OSCC patients, adjacent noncancerous oral tissue from 79 OSCC patients, and normal oral mucosa from 35 control patients were examined for Ang-2 and VEGF expression using conventional immunohistochemistry. Microvessel density (MVD) and vessel maturation index (VMI) were assessed by double-label immunohistochemistry staining using anti-CD34 and anti-alpha-smooth muscle actin, respectively. Although the proportion of OSCC samples positive for Ang-2 or VEGF expression was significantly higher than that observed in the adjacent noncancerous tissue and normal oral mucosa (P < 0.001), neither Ang-2 nor VEGF expression was associated with the clinicopathological parameters analyzed in OSCC patients. However, MVD and VMI were significantly associated with the expression of Ang-2 (P = 0.001 and P = 0.014, respectively); VEGF expression was associated MVD (P = 0.004). The MVD of OSCC tissues expressing both Ang-2 and VEGF was significantly higher than observed in the double-negative samples (P < 0.05). Multivariate regression and Kaplan–Meier analyses revealed that Ang-2 was negatively associated with the overall survival of OSCC patients. Expression of Ang-2 was associated with angiogenesis and vessel maturation in OSCC. Further studies will evaluate the prognostic value of determining Ang-2 expression in OSCC.
Literatur
1.
Zurück zum Zitat Zygogianni AG, Kyrgias G, Karakitsos P, Psyrri A, Kouvaris J, Kelekis N, et al. Oral squamous cell cancer: early detection and the role of alcohol and smoking. Head Neck Oncol. 2011;3:2.CrossRefPubMed Zygogianni AG, Kyrgias G, Karakitsos P, Psyrri A, Kouvaris J, Kelekis N, et al. Oral squamous cell cancer: early detection and the role of alcohol and smoking. Head Neck Oncol. 2011;3:2.CrossRefPubMed
2.
Zurück zum Zitat Li C, Chen JC, Wang ZH, Zhang B, Li B, Song YF. The characteristics and significance of microvessel in oral squamous cell carcinoma. Zhonghua Kou Qiang Yi Xue Za Zhi. 2007;42:70–3.PubMed Li C, Chen JC, Wang ZH, Zhang B, Li B, Song YF. The characteristics and significance of microvessel in oral squamous cell carcinoma. Zhonghua Kou Qiang Yi Xue Za Zhi. 2007;42:70–3.PubMed
3.
Zurück zum Zitat Li C, Feng HC, Chen JC, Song YF. Expression and significance of angiopoietin-1 and angiopoietin-2 in oral squamous cell carcinoma. Ai Zheng. 2005;24:1388–93.PubMed Li C, Feng HC, Chen JC, Song YF. Expression and significance of angiopoietin-1 and angiopoietin-2 in oral squamous cell carcinoma. Ai Zheng. 2005;24:1388–93.PubMed
4.
Zurück zum Zitat Johnstone S, Logan RM. Expression of vascular endothelial growth factor (VEGF) in normal oral mucosa, oral dysplasia and oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2007;36:263–6.CrossRefPubMed Johnstone S, Logan RM. Expression of vascular endothelial growth factor (VEGF) in normal oral mucosa, oral dysplasia and oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2007;36:263–6.CrossRefPubMed
5.
Zurück zum Zitat Lopez-Graniel CM, Tamez de Leon D, Meneses-Garcia A, Gómez-Ruiz C, Frias-Mendivil M, Granados-García M, et al. Tumor angiogenesis as a prognostic factor in oral cavity carcinomas. Exp Clin Cancer Res. 2001;20:463–8. Lopez-Graniel CM, Tamez de Leon D, Meneses-Garcia A, Gómez-Ruiz C, Frias-Mendivil M, Granados-García M, et al. Tumor angiogenesis as a prognostic factor in oral cavity carcinomas. Exp Clin Cancer Res. 2001;20:463–8.
6.
7.
Zurück zum Zitat Sakurai T, Kudo M. Signaling pathways governing tumor angiogenesis. Oncology. 2011;1:24–9.CrossRef Sakurai T, Kudo M. Signaling pathways governing tumor angiogenesis. Oncology. 2011;1:24–9.CrossRef
8.
Zurück zum Zitat Saharinen P, Eklund L, Pulkki K, Bono P, Alitalo K. VEGF and angiopoietin signaling in tumor angiogenesis and metastasis. Trends Mol Med. 2011;17:347–62.CrossRefPubMed Saharinen P, Eklund L, Pulkki K, Bono P, Alitalo K. VEGF and angiopoietin signaling in tumor angiogenesis and metastasis. Trends Mol Med. 2011;17:347–62.CrossRefPubMed
9.
Zurück zum Zitat Johnstone S, Logan RM. The role of vascular endothelial growth factor (VEGF) in oral dysplasia and oral squamous cell carcinoma. Oral Oncol. 2006;42:337–42.CrossRefPubMed Johnstone S, Logan RM. The role of vascular endothelial growth factor (VEGF) in oral dysplasia and oral squamous cell carcinoma. Oral Oncol. 2006;42:337–42.CrossRefPubMed
10.
Zurück zum Zitat Asahara T, Chen D, Takahashi T, Fujikawa K, Kearney M, Magner M, et al. Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization. Circ Res. 1998;83:233–40.CrossRefPubMed Asahara T, Chen D, Takahashi T, Fujikawa K, Kearney M, Magner M, et al. Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization. Circ Res. 1998;83:233–40.CrossRefPubMed
11.
Zurück zum Zitat Feng Y, vom Hagen F, Pfister F, Djokic S, Hoffmann S, Back W, et al. Impaired pericyte recruitment and abnormal retinal angiogenesis as a result of angiopoietin-2 overexpression. Thromb Haemost. 2007;97:99–108.PubMed Feng Y, vom Hagen F, Pfister F, Djokic S, Hoffmann S, Back W, et al. Impaired pericyte recruitment and abnormal retinal angiogenesis as a result of angiopoietin-2 overexpression. Thromb Haemost. 2007;97:99–108.PubMed
12.
Zurück zum Zitat Thomas M, Augustin HG. The role of the angiopoietins in vascular morphogenesis. Angiogenesis. 2009;12:125–37.CrossRefPubMed Thomas M, Augustin HG. The role of the angiopoietins in vascular morphogenesis. Angiogenesis. 2009;12:125–37.CrossRefPubMed
13.
Zurück zum Zitat Shim WSN, Ho IAW, Wong PEH. Angiopoietin A TIE(d) balance in tumor angiogenesis. Mol Cancer Res. 2007;5:655–65.CrossRefPubMed Shim WSN, Ho IAW, Wong PEH. Angiopoietin A TIE(d) balance in tumor angiogenesis. Mol Cancer Res. 2007;5:655–65.CrossRefPubMed
14.
Zurück zum Zitat Koga K, Todaka T, Morioka M, Hamada J, Kai Y, Yano S, et al. Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis. Cancer Res. 2001;61:6248–54.PubMed Koga K, Todaka T, Morioka M, Hamada J, Kai Y, Yano S, et al. Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis. Cancer Res. 2001;61:6248–54.PubMed
15.
Zurück zum Zitat Ochiumi T, Tanaka S, Oka S, Hiyama T, Ito M, Kitadai Y, et al. Clinical significance of angiopoietin-2 expression at the deepest invasive tumor site of advanced colorectal carcinoma. Int J Oncol. 2004;24:539–47.PubMed Ochiumi T, Tanaka S, Oka S, Hiyama T, Ito M, Kitadai Y, et al. Clinical significance of angiopoietin-2 expression at the deepest invasive tumor site of advanced colorectal carcinoma. Int J Oncol. 2004;24:539–47.PubMed
16.
Zurück zum Zitat Ahmad SA, Liu W, Jung YD, Fan F, Wilson M, Reinmuth N, et al. The effects of angiopoietin-1 and -2on tumor growth and angiogenesis in human colon cancer. Cancer Res. 2001;61:1255–9.PubMed Ahmad SA, Liu W, Jung YD, Fan F, Wilson M, Reinmuth N, et al. The effects of angiopoietin-1 and -2on tumor growth and angiogenesis in human colon cancer. Cancer Res. 2001;61:1255–9.PubMed
17.
Zurück zum Zitat Yoshida Y, Oshika Y, Fukushima Y, Tokunaga T, Hatanaka H, Kijima H, et al. Expression of angiostatic factors in colorectal cancer. Int J Oncol. 1999;15:1221–5.PubMed Yoshida Y, Oshika Y, Fukushima Y, Tokunaga T, Hatanaka H, Kijima H, et al. Expression of angiostatic factors in colorectal cancer. Int J Oncol. 1999;15:1221–5.PubMed
18.
Zurück zum Zitat Oka N, Yamamoto Y, Takahashi M, Nishitani M, Kanayama HO, Kagawa S. Expression of angiopoietin-1 and -2, and its clinical significance in human bladder cancer. BJU Int. 2005;95:660–3.CrossRefPubMed Oka N, Yamamoto Y, Takahashi M, Nishitani M, Kanayama HO, Kagawa S. Expression of angiopoietin-1 and -2, and its clinical significance in human bladder cancer. BJU Int. 2005;95:660–3.CrossRefPubMed
19.
Zurück zum Zitat Tanaka F, Ishikawa S, Yanagihara K, Miyahara R, Kawano Y, Li M, et al. Expression of angiopoietins and its clinical significance in non-small cell lung cancer. Cancer Res. 2002;62:7124–9.PubMed Tanaka F, Ishikawa S, Yanagihara K, Miyahara R, Kawano Y, Li M, et al. Expression of angiopoietins and its clinical significance in non-small cell lung cancer. Cancer Res. 2002;62:7124–9.PubMed
20.
Zurück zum Zitat Helfrich I, Edler L, Sucker A, Thomas M, Christian S, Schadendorf D, et al. Angiopoietin-2 levels are associated with disease progression in metastatic malignant melanoma. Clin Cancer Res. 2009;15:1384–92.CrossRefPubMed Helfrich I, Edler L, Sucker A, Thomas M, Christian S, Schadendorf D, et al. Angiopoietin-2 levels are associated with disease progression in metastatic malignant melanoma. Clin Cancer Res. 2009;15:1384–92.CrossRefPubMed
21.
Zurück zum Zitat Yu Q, Stamenkovic I. Angiopoietin-2 is implicated in the regulation of tumor angiogenesis. Am J Pathol. 2001;158:563–70.CrossRefPubMed Yu Q, Stamenkovic I. Angiopoietin-2 is implicated in the regulation of tumor angiogenesis. Am J Pathol. 2001;158:563–70.CrossRefPubMed
22.
Zurück zum Zitat Tanaka S, Mori M, Sakamoto Y, Makuuchi M, Sugimachi K, Wands JR. Biologic significance of angiopoietin-2 expression in human hepatocellular carcinoma. J Clin Invest. 1999;103:341–5.CrossRefPubMed Tanaka S, Mori M, Sakamoto Y, Makuuchi M, Sugimachi K, Wands JR. Biologic significance of angiopoietin-2 expression in human hepatocellular carcinoma. J Clin Invest. 1999;103:341–5.CrossRefPubMed
23.
Zurück zum Zitat Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science. 1999;284:1994–8.CrossRefPubMed Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science. 1999;284:1994–8.CrossRefPubMed
24.
Zurück zum Zitat Wakui S, Yokoo K, Muto T, Suzuki Y, Takahashi H, Furusato M, et al. Localization of Ang-1, -2, Tie-2, and VEGF expression at endothelial-pericyte interdigitation in rat angiogenesis. Lab Invest. 2006;86:1172–84.PubMed Wakui S, Yokoo K, Muto T, Suzuki Y, Takahashi H, Furusato M, et al. Localization of Ang-1, -2, Tie-2, and VEGF expression at endothelial-pericyte interdigitation in rat angiogenesis. Lab Invest. 2006;86:1172–84.PubMed
25.
Zurück zum Zitat Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17:1471–4.CrossRefPubMed Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17:1471–4.CrossRefPubMed
26.
Zurück zum Zitat Bryne M, Koppang HS, Lilleng R, Kjaerheim A. Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value. J Pathol. 1992;166:375–81.CrossRefPubMed Bryne M, Koppang HS, Lilleng R, Kjaerheim A. Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value. J Pathol. 1992;166:375–81.CrossRefPubMed
27.
Zurück zum Zitat Eberhard A, Kahlert S, Goede V. Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. Cancer Res. 2000;60:1388–93.PubMed Eberhard A, Kahlert S, Goede V. Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. Cancer Res. 2000;60:1388–93.PubMed
28.
Zurück zum Zitat Koga K, Todaka T, Morioka M, Hamada J, Kai Y, Yano S, et al. Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis. Cancer Res. 2001;61:6248–54.PubMed Koga K, Todaka T, Morioka M, Hamada J, Kai Y, Yano S, et al. Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis. Cancer Res. 2001;61:6248–54.PubMed
29.
Zurück zum Zitat Ochiumi T, Tanaka S, Oka S, Hiyama T, Ito M, Kitadai Y, et al. Clinical significance of angiopoietin-2 expression at the deepest invasive tumor site of advanced colorectal carcinoma. Int J Oncol. 2004;24:539–47.PubMed Ochiumi T, Tanaka S, Oka S, Hiyama T, Ito M, Kitadai Y, et al. Clinical significance of angiopoietin-2 expression at the deepest invasive tumor site of advanced colorectal carcinoma. Int J Oncol. 2004;24:539–47.PubMed
30.
Zurück zum Zitat Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 1995;36:169–80.CrossRefPubMed Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 1995;36:169–80.CrossRefPubMed
31.
Zurück zum Zitat He LL, Zhang WJ, Su H, Xu DG. Synergism between Ang-2 and VEGF and its application of anti-angiogenesis in tumor therapy. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007;15:445–8.PubMed He LL, Zhang WJ, Su H, Xu DG. Synergism between Ang-2 and VEGF and its application of anti-angiogenesis in tumor therapy. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007;15:445–8.PubMed
32.
Zurück zum Zitat Mărgăritescu C, Pirici D, Stîngă A, Simionescu C, Raica M, Mogoantă L, et al. VEGF expression and angiogenesis in oral squamous cell carcinoma: an immunohistochemical and morphometric study. Clin Exp Med. 2010;10:209–14.CrossRefPubMed Mărgăritescu C, Pirici D, Stîngă A, Simionescu C, Raica M, Mogoantă L, et al. VEGF expression and angiogenesis in oral squamous cell carcinoma: an immunohistochemical and morphometric study. Clin Exp Med. 2010;10:209–14.CrossRefPubMed
33.
Zurück zum Zitat Conklin LD, McAninch RE, Schulz D, Kaluza GL, LeMaire SA, Coselli JS, et al. HIV-based vectors and angiogenesis following rabbit hindlimb ischemia. J Surg Res. 2005;123:55–66.CrossRefPubMed Conklin LD, McAninch RE, Schulz D, Kaluza GL, LeMaire SA, Coselli JS, et al. HIV-based vectors and angiogenesis following rabbit hindlimb ischemia. J Surg Res. 2005;123:55–66.CrossRefPubMed
34.
Zurück zum Zitat Ley CD, Olsen MW, Lund EL, Kristjansen PE. Angiogenic synergy of bFGF and VEGF is antagonized by angiopoietin-2in a modified in vivo matrigel assay. Microvasc Res. 2004;68:161–8.CrossRefPubMed Ley CD, Olsen MW, Lund EL, Kristjansen PE. Angiogenic synergy of bFGF and VEGF is antagonized by angiopoietin-2in a modified in vivo matrigel assay. Microvasc Res. 2004;68:161–8.CrossRefPubMed
35.
Zurück zum Zitat Machein MR, Knedla A, Knoth R, Wagner S, Neuschl E, Plate KH. Angiopoietin-1 promotes tumor angiogenesis in a rat glioma model. Am J Pathol. 2004;165:1557–70.CrossRefPubMed Machein MR, Knedla A, Knoth R, Wagner S, Neuschl E, Plate KH. Angiopoietin-1 promotes tumor angiogenesis in a rat glioma model. Am J Pathol. 2004;165:1557–70.CrossRefPubMed
36.
Zurück zum Zitat Etoh T, Inoue H, Tanaka S, Barnard GF, Kitano S, Mori M. Angiopoietin-2 is related to tumor angiogenesis in gastric carcinoma: possible in vivo regulation via induction of proteases. Cancer Res. 2001;61:2145–53.PubMed Etoh T, Inoue H, Tanaka S, Barnard GF, Kitano S, Mori M. Angiopoietin-2 is related to tumor angiogenesis in gastric carcinoma: possible in vivo regulation via induction of proteases. Cancer Res. 2001;61:2145–53.PubMed
37.
Zurück zum Zitat Chien CY, Su CY, Chuang HC, Fang FM, Huang HY, Chen CM, et al. Angiopoietin-1 and -2 expression in recurrent squamous cell carcinoma of the oral cavity. J Surg Oncol. 2008;97:273–7.CrossRefPubMed Chien CY, Su CY, Chuang HC, Fang FM, Huang HY, Chen CM, et al. Angiopoietin-1 and -2 expression in recurrent squamous cell carcinoma of the oral cavity. J Surg Oncol. 2008;97:273–7.CrossRefPubMed
38.
Zurück zum Zitat Cheng SJ, Lee JJ, Kok SH, Chou CH, Chang HH, Yang H, et al. Expression of vascular endothelial growth factor is significantly associated with progression and prognosis of oral squamous cell carcinomas in Taiwan. J Formos Med Assoc. 2011;110:50–7.CrossRefPubMed Cheng SJ, Lee JJ, Kok SH, Chou CH, Chang HH, Yang H, et al. Expression of vascular endothelial growth factor is significantly associated with progression and prognosis of oral squamous cell carcinomas in Taiwan. J Formos Med Assoc. 2011;110:50–7.CrossRefPubMed
39.
Zurück zum Zitat Chien CY, Su CY, Hwang CF, Chuang HC, Chen CM, Huang CC. High expressions of CD105 and VEGF in early oral cancer predict potential cervical metastasis. Surg Oncol. 2006;94:413–7.CrossRef Chien CY, Su CY, Hwang CF, Chuang HC, Chen CM, Huang CC. High expressions of CD105 and VEGF in early oral cancer predict potential cervical metastasis. Surg Oncol. 2006;94:413–7.CrossRef
40.
Zurück zum Zitat Shao Z, Zhang WF, Chen XM, Shang ZJ. Expression of EphA2 and VEGF in squamous cell carcinoma of the tongue: correlation with the angiogenesis and clinical outcome. Oral Oncol. 2008;44:1110–7.CrossRefPubMed Shao Z, Zhang WF, Chen XM, Shang ZJ. Expression of EphA2 and VEGF in squamous cell carcinoma of the tongue: correlation with the angiogenesis and clinical outcome. Oral Oncol. 2008;44:1110–7.CrossRefPubMed
41.
Zurück zum Zitat Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 1995;36:169–80.CrossRefPubMed Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 1995;36:169–80.CrossRefPubMed
42.
Zurück zum Zitat Zagzag D, Amirnovin R, Greco MA, Yee H, Holash J, Wiegand SJ, et al. Vascular apoptosis and involution in gliomas precede neovascularization: a novel concept for glioma growth and angiogenesis. Lab Invest. 2000;80:837–49.CrossRefPubMed Zagzag D, Amirnovin R, Greco MA, Yee H, Holash J, Wiegand SJ, et al. Vascular apoptosis and involution in gliomas precede neovascularization: a novel concept for glioma growth and angiogenesis. Lab Invest. 2000;80:837–49.CrossRefPubMed
43.
Zurück zum Zitat Gee MS, Procopio WN, Makonnen S. Tumor vessel development and maturation impose limits on the effectiveness of anti-vascular therapy. Am J Pathol. 2003;162:183–93.CrossRefPubMed Gee MS, Procopio WN, Makonnen S. Tumor vessel development and maturation impose limits on the effectiveness of anti-vascular therapy. Am J Pathol. 2003;162:183–93.CrossRefPubMed
44.
Zurück zum Zitat Chechlinska M, Kowalewska M, Nowak R. Systemic inflammation as a confounding factor in cancer biomarker discovery and validation. Nat Rev Cancer. 2010;10:2–3.CrossRefPubMed Chechlinska M, Kowalewska M, Nowak R. Systemic inflammation as a confounding factor in cancer biomarker discovery and validation. Nat Rev Cancer. 2010;10:2–3.CrossRefPubMed
Metadaten
Titel
Angiopoietin-2 expression is correlated with angiogenesis and overall survival in oral squamous cell carcinoma
verfasst von
Chao Li
Chang-jin Sun
Jin-chuan Fan
Ning Geng
Chun-hua Li
Jian Liao
Kun Mi
Gui-quan Zhu
Hong Ma
Yu-feng Song
Ya-ling Tang
Yu Chen
Publikationsdatum
01.06.2013
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 2/2013
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0571-2

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