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Expression of endoglin and podoplanin in early and advanced oral squamous cell carcinoma

  • Lee, Sang-Woon (Department of Oral and Maxillofacial Surgery, School of Dentistry, Gangneung-Wonju National University) ;
  • Park, Young-Wook (Department of Oral and Maxillofacial Surgery, School of Dentistry, Gangneung-Wonju National University)
  • Received : 2012.01.27
  • Accepted : 2012.05.03
  • Published : 2012.06.30

Abstract

Objectives: Angiogenesis and lymphangiogenesis are correlated with tumor growth and lymph node metastasis in cases of oral squamous cell carcinoma (OSCC). Endoglin is one of the representative vascular endothelial cell markers. Podoplanin is also a representative marker used in order to detect lymphatic endothelial cells. The aim of this study was to determine the correlation between the expression of endoglin/podoplanin and clinical variables associated with OSCC progression. Materials and Methods: Paraffin embedded tissue specimens from 21 patients diagnosed with OSCC were used in this study. Ten patients were diagnosed with early clinical stage (I or II) and 11 patients with advanced clinical stage (III or IV) OSCC. Five patients had positive lymph node involvement. Primary antibodies for endoglin and podoplanin were used to perform the immunohistochemical detection of the vascular and lymphatic endothelial cells. The expression of endoglin and podoplanin was examined by an image analysis program in the three most highly expressed regions of each specimen. Results: The average endoglin expression was observed to be $1.691{\pm}0.920$ in the advanced stage (III, IV) specimens and $0.797{\pm}0.583$ in the early stage (I, II) specimens (P=0.020). The average expression of podoplanin was $0.286{\pm}0.228$ in the advance stage (III, IV) specimens and $0.374{\pm}0.157$ in the early stage (I, II) specimens (P>0.05). There was no statistically significant difference in the expression of endoglin and podoplanin, regardless of whether or not the lymph node was positive. Conclusion: The expression of endoglin was significantly higher in the advanced stage specimens than that in the early stage specimens. Therefore, we concluded that endoglin is a useful molecular marker for use in the evaluation of the progression of OSCC.

Keywords

References

  1. McDowell JD. An overview of epidemiology and common risk factors for oral squamous cell carcinoma. Otolaryngol Clin North Am 2006;39:277-94.
  2. Scully C, Field JK, Tanzawa H. Genetic aberrations in oral or head and neck squamous cell carcinoma 2: chromosomal aberrations. Oral Oncol 2000;36:311-27.
  3. Scully C, Field JK, Tanzawa H. Genetic aberrations in oral or head and neck squamous cell carcinoma (SCCHN): 1. Carcinogen metabolism, DNA repair and cell cycle control. Oral Oncol 2000;36:256-63.
  4. Oliveira LR, Ribeiro-Silva A. Prognostic significance of immunohistochemical biomarkers in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 2011;40:298-307.
  5. Scully C, Bagan JV. Recent advances in oral oncology 2008; squamous cell carcinoma imaging, treatment, prognostication and treatment outcomes. Oral Oncol 2009;45:e25-30.
  6. Massano J, Regateiro FS, Januario G, Ferreira A. Oral squamous cell carcinoma: review of prognostic and predictive factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102:67-76.
  7. van der Schroeff MP, Baatenburg de Jong RJ. Staging and prognosis in head and neck cancer. Oral Oncol 2009;45:356-60.
  8. Kim JY, Rotaru H, Kim SG. The clinical significance of the expression of TGF-beta 1 and MMP-2 related to the regional lymph node metastasis in the oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg 2007;33:199-203.
  9. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407:249-57.
  10. Hasina R, Lingen MW. Angiogenesis in oral cancer. J Dent Educ 2001;65:1282-90.
  11. Palomba A, Gallo O, Brahimi A, Franchi A. Evaluation of lymphangiogenesis in premalignant conditions of the head and neck mucosa. Head Neck 2010;32:1681-5.
  12. Mumprecht V, Detmar M. Lymphangiogenesis and cancer metastasis. J Cell Mol Med 2009;13:1405-16.
  13. Duff SE, Li C, Garland JM, Kumar S. CD105 is important for angiogenesis: evidence and potential applications. FASEB J 2003;17:984-92.
  14. Raica M, Cimpean AM, Ribatti D. The role of podoplanin in tumor progression and metastasis. Anticancer Res 2008;28:2997-3006.
  15. Kyzas PA, Agnantis NJ, Stefanou D. Endoglin (CD105) as a prognostic factor in head and neck squamous cell carcinoma. Virchows Arch 2006;448:768-75.
  16. Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. N Engl J Med 1991;324:1-8.
  17. Zhang Z, Helman JI, Li LJ. Lymphangiogenesis, lymphatic endothelial cells and lymphatic metastasis in head and neck cancer--a review of mechanisms. Int J Oral Sci 2010;2:5-14.
  18. Sundar SS, Ganesan TS. Role of lymphangiogenesis in cancer. J Clin Oncol 2007;25:4298-307.
  19. Tortora G, Melisi D, Ciardiello F. Angiogenesis: a target for cancer therapy. Curr Pharm Des 2004;10:11-26.
  20. Dredge K, Dalgleish AG, Marriott JB. Angiogenesis inhibitors in cancer therapy. Curr Opin Investig Drugs 2003;4:667-74.
  21. Madhusudan S, Harris AL. Drug inhibition of angiogenesis. Curr Opin Pharmacol 2002;2:403-14.
  22. Rugo HS. Bevacizumab in the treatment of breast cancer: rationale and current data. Oncologist 2004;9 Suppl 1:43-9.
  23. Planchard D. Bevacizumab in non-small-cell lung cancer: a review. Expert Rev Anticancer Ther 2011;11:1163-79.
  24. Tappenden P, Jones R, Paisley S, Carroll C. Systematic review and economic evaluation of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer. Health Technol Assess 2007;11:1-128.
  25. Lastres P, Letamendia A, Zhang H, Rius C, Almendro N, Raab U, et al. Endoglin modulates cellular responses to TGF-beta 1. J Cell Biol 1996;133:1109-21.
  26. Quintanilla M, Ramirez JR, Perez-Gomez E, Romero D, Velasco B, Letarte M, et al. Expression of the TGF-beta coreceptor endoglin in epidermal keratinocytes and its dual role in multistage mouse skin carcinogenesis. Oncogene 2003;22:5976-85.
  27. Arthur HM, Ure J, Smith AJ, Renforth G, Wilson DI, Torsney E, et al. Endoglin, an ancillary TGFbeta receptor, is required for extraembryonic angiogenesis and plays a key role in heart development. Dev Biol 2000;217:42-53.
  28. Li DY, Sorensen LK, Brooke BS, Urness LD, Davis EC, Taylor DG, et al. Defective angiogenesis in mice lacking endoglin. Science 1999;284:1534-7.
  29. Schimming R, Reusch P, Kuschnierz J, Schmelzeisen R. Angiogenic factors in squamous cell carcinoma of the oral cavity: do they have prognostic relevance? J Craniomaxillofac Surg 2004;32:176-81.
  30. Schimming R, Marme D. Endoglin (CD105) expression in squamous cell carcinoma of the oral cavity. Head Neck 2002;24:151-6.
  31. Eshghyar N, Mohammadi N, Rahrotaban S, Motahhary P, Vahedi Vaez SM. Endoglin (CD105) positive microvessel density and its relationship with lymph node metastasis in squamous cell carcinoma of the tongue. Arch Iran Med 2011;14:276-80.
  32. Chuang HC, Su CY, Huang HY, Chien CY, Chen CM, Huang CC. High expression of CD105 as a prognostic predictor of early tongue cancer. Laryngoscope 2006;116:1175-9.
  33. Wicki A, Christofori G. The potential role of podoplanin in tumour invasion. Br J Cancer 2007;96:1-5.
  34. Funayama A, Cheng J, Maruyama S, Yamazaki M, Kobayashi T, Syafriadi M, et al. Enhanced expression of podoplanin in oral carcinomas in situ and squamous cell carcinomas. Pathobiology 2011;78:171-80.
  35. Siriwardena BS, Kudo Y, Ogawa I, Udagama MN, Tilakaratne WM, Takata T. VEGF-C is associated with lymphatic status and invasion in oral cancer. J Clin Pathol 2008;61:103-8.
  36. Zhang Z, Pan J, Li L, Wang Z, Xiao W, Li N. Survey of risk factors contributed to lymphatic metastasis in patients with oral tongue cancer by immunohistochemistry. J Oral Pathol Med 2011; 40:127-34.
  37. Okada Y. Relationships of cervical lymph node metastasis to histopathological malignancy grade, tumor angiogenesis, and lymphatic invasion in tongue cancer. Odontology 2010;98:153-9.
  38. Zhao D, Pan J, Li XQ, Wang XY, Tang C, Xuan M. Intratumoral lymphangiogenesis in oral squamous cell carcinoma and its clinicopathological significance. J Oral Pathol Med 2008;37:616-25.
  39. Longatto Filho A, Oliveira TG, Pinheiro C, de Carvalho MB, Curioni OA, Mercante AM, et al. How useful is the assessment of lymphatic vascular density in oral carcinoma prognosis? World J Surg Oncol 2007;5:140.
  40. Miyahara M, Tanuma J, Sugihara K, Semba I. Tumor lymphangiogenesis correlates with lymph node metastasis and clinico pathologic parameters in oral squamous cell carcinoma. Cancer 2007;110:1287-94.
  41. Kreppel M, Scheer M, Drebber U, Ritter L, Zoller JE. Impact of podoplanin expression in oral squamous cell carcinoma: clinical and histopathologic correlations. Virchows Arch 2010;456:473-82.
  42. Yuan P, Temam S, El-Naggar A, Zhou X, Liu DD, Lee JJ, et al. Overexpression of podoplanin in oral cancer and its association with poor clinical outcome. Cancer 2006;107:563-9.
  43. Huber GF, Fritzsche FR, Zullig L, Storz M, Graf N, Haerle SK, et al. Podoplanin expression correlates with sentinel lymph node metastasis in early squamous cell carcinomas of the oral cavity and oropharynx. Int J Cancer 2011;129:1404-9.
  44. Kanner WA, Galgano MT, Atkins KA. Podoplanin expression in basal and myoepithelial cells: utility and potential pitfalls. Appl Immunohistochem Mol Morphol 2010;18:226-30.
  45. Van der Auwera I, Cao Y, Tille JC, Pepper MS, Jackson DG, Fox SB, et al. First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours. Br J Cancer 2006;95:1611-25.
  46. Choi WW, Lewis MM, Lawson D, Yin-Goen Q, Birdsong GG, Cotsonis GA, et al. Angiogenic and lymphangiogenic microvessel density in breast carcinoma: correlation with clinicopathologic parameters and VEGF-family gene expression. Mod Pathol 2005;18:143-52.

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