Skip to main content

Advertisement

SpringerLink
Log in

Endoglin (CD105) as a prognostic factor in head and neck squamous cell carcinoma

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Endoglin (CD105) is a proliferation-associated protein abundantly expressed in angiogenic endothelial cells. Recent studies revealed that CD105 is intensively expressed in tumor vasculature, whereas intratumoral microvessel density (MVD) determined with the use of antibodies to CD105 has been found to be an important prognostic indicator for the outcome in a number of malignancies. In the current study, we investigated endoglin expression and evaluated MVD in 108 patients with head and neck squamous cell carcinoma. Endoglin was intensively expressed in intratumoral blood vessels, whilst lymphatics were rarely positive for CD105. High microvessel density was associated with a more aggressive tumor phenotype, including advanced clinical stage (p=0.008) and the presence of lymph node metastasis at the time of diagnosis (p=0.02). When microvessel counts were assessed for their prognostic values (high vs low MVD), there was a statistically significant difference in the overall survival among patients with tumors of the oral cavity and larynx (p<0.001) and in the disease-free survival among patients with tumors of the lower lip (p=0.01). The prognostic impact of microvessel density was not dependent on clinical stage or lymph node status. The results of the current study suggest that CD105 is a promising target for tumor imaging and prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Aebersold DM, Beer KT, Laissue J, Hug S, Kollar A, Greiner RH, Djonov V (2000) Intratumoral microvessel density predicts local treatment failure of radically irradiated squamous cell cancer of the oropharynx. Int J Radiat Oncol Biol Phys 48:17–25

    Article  PubMed  CAS  Google Scholar 

  2. Altman DG, Lausen B, Sauerbrei W, Schumacher M (1994) Dangers of using “optimal” cutpoints in the evaluation of prognostic factors. J Natl Cancer Inst 86:829–835

    Article  PubMed  CAS  Google Scholar 

  3. Brattstrom D, Bergqvist M, Wester K, Hesselius P, Ren ZP, Scheibenpflug L, Wagenius G, Brodin O (2004) Endothelial markers and circulating angiogenic factors and p53 may be potential markers for recurrence in surgically resected non-small cell lung cancer patients. Med Sci Monit 10:331–338

    Google Scholar 

  4. Brewer CA, Setterdahl JJ, Li MJ, Johnston JM, Mann JL, McAsey ME (2000) Endoglin expression as a measure of microvessel density in cervical cancer. Obstet Gynecol 96:224–228

    Article  PubMed  CAS  Google Scholar 

  5. Chien CY, Su CY, Hwang CF, Chuang HC, Hsiao YC, Wu SL, Huang CC (2005) Clinicopathologic significance of CD105 expression in squamous cell carcinoma of the hypopharynx. Head Neck 2005 (In press)

  6. Costello B, Li C, Duff S, Butterworth D, Khan A, Perkins M, Owens S, Al-Mowallad AF, O’Dwyer S, Kumar S (2004) Perfusion of 99Tcm-labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target. Int J Cancer 109:436–441

    Article  PubMed  CAS  Google Scholar 

  7. Dales JP, Garcia S, Carpentier S, Andrac L, Ramuz O, Lavaut MN, Allasia C, Bonnier P, Charpin C (2004) Long-term prognostic significance of neoangiogenesis in breast carcinomas: comparison of Tie-2/Tek, CD105, and CD31 immunocytochemical expression. Hum Pathol 35:176–183

    Article  PubMed  CAS  Google Scholar 

  8. Duff SE, Li C, Garland JM, Kumar S (2003) CD105 is important for angiogenesis: evidence and potential applications. FASEB J 17:984–992

    Article  PubMed  CAS  Google Scholar 

  9. Ellis LM, Liu W, Fan F, Reinmuth N, Shaheen RM, Jung YD, Ahmad S (2001) Role of angiogenesis inhibitors in cancer treatment. Oncology (Huntingt) 15:39–46

    CAS  Google Scholar 

  10. Evangelou E, Kyzas PA, Trikalinos TA (2005) Comparison of the diagnostic accuracy of lymphatic endothelium markers: Bayesian approach. Mod Pathol 18:1490–1497

    Article  PubMed  CAS  Google Scholar 

  11. Folkman J (1990) What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82:4–6

    Article  PubMed  CAS  Google Scholar 

  12. Fonsatti E, Del Vecchio L, Altomonte M, Sigalotti L, Nicotra MR, Coral S, Natali PG, Maio M (2001) Endoglin: an accessory component of the TGF-beta-binding receptor-complex with diagnostic, prognostic, and bioimmunotherapeutic potential in human malignancies. J Cell Physiol 1888:1–7

    Article  Google Scholar 

  13. Fonsatti E, Altomonte M, Nicotra MR, Natali PG, Maio M (2003) Endoglin (CD105): a powerful therapeutic target on tumor-associated angiogenetic blood vessels. Oncogene 22:6557–6563

    Article  PubMed  CAS  Google Scholar 

  14. Fonsatti E, Maio M (2004) Highlights on endoglin (CD105): from basic findings towards clinical applications in human cancer. J Transl Med 2:18–25

    Article  PubMed  Google Scholar 

  15. Gallo O, Masini E, Bianchi B, Bruschini L, Paglierani M, Franchi A (2002) Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma. Hum Pathol 33:708–714

    Article  PubMed  CAS  Google Scholar 

  16. Hirakawa S, Hong YK, Harvey N, Schacht V, Matsuda K, Libermann T, Detmar M (2003) Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells. Am J Pathol 162:575–586

    PubMed  CAS  Google Scholar 

  17. Hong WK, Lippman SM, Itri LM, Karp DD, Lee JS, Byers RM, Schantz SP, Kramer AM, Lotan R, Peters LJ (1990) Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323:795–801

    Article  PubMed  CAS  Google Scholar 

  18. Kumar S, Ghellal A, Li C, Byrne G, Haboubi N, Wang JM, Bundred N (1999) Breast carcinoma: vascular density determined using CD105 antibody correlates with tumor prognosis. Cancer Res 59:856–861

    PubMed  CAS  Google Scholar 

  19. Kyzas PA, Stefanou D, Agnantis NJ (2004) Immunohistochemical expression of vascular endothelial growth factor correlates with positive surgical margins and recurrence in T1 and T2 squamous cell carcinoma (SCC) of the lower lip. Oral Oncol 40:941–947

    Article  PubMed  CAS  Google Scholar 

  20. Kyzas PA, Geleff S, Batistatou A, Agnantis NJ, Stefanou D (2005) Evidence for lymphangiogenesis and its prognostic implications in head and neck squamous cell carcinoma. J Pathol 206:170–177

    Article  PubMed  Google Scholar 

  21. Kyzas PA, Loizou KT, Ioannidis JP (2005) Selective reporting biases in cancer prognostic factor studies. J Natl Cancer Inst 97:1043–1055

    Article  PubMed  Google Scholar 

  22. Kyzas PA, Stefanou D, Agnantis NJ (2005) COX-2 expression correlates with VEGF-C and lymph node metastases in patients with head and neck squamous cell carcinoma. Mod Pathol 18:153–160

    Article  PubMed  CAS  Google Scholar 

  23. Kyzas PA, Stefanou D, Batistatou A, Agnantis NJ (2005) Prognostic significance of VEGF immunohistochemical expression and tumor angiogenesis in head and neck squamous cell carcinoma. J Cancer Res Clin Oncol 131:624–630

    Article  PubMed  CAS  Google Scholar 

  24. Kyzas PA, Cunha IW, Ioannidis JP (2005) Prognostic significance of vascular endothelial growth factor immunohistochemical expression in head and neck squamous cell carcinoma: a meta-analysis. Clin Cancer Res 11:1434–1440

    Article  PubMed  CAS  Google Scholar 

  25. Kyzas PA, Stefanou D, Batistatou A, Agnantis NJ (2005) Hypoxia-induced tumor angiogenic pathway in head and neck cancer: an in vivo study. Cancer Lett 225:297–304

    Article  PubMed  CAS  Google Scholar 

  26. Li C, Gardy R, Seon BK, Duff SE, Abdalla S, Renehan A, O’Dwyer ST, Haboubi N, Kumar S (2003) Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis. Br J Cancer 88:1424–1431

    Article  PubMed  CAS  Google Scholar 

  27. Marioni G, Gaio E, Giacomelli L, Marchese-Ragona R, Staffieri C, Staffieri A, Marino F (2005) Endoglin (CD105) expression in head and neck basaloid squamous cell carcinoma. Acta Otolaryngol 125:307–311

    Article  PubMed  CAS  Google Scholar 

  28. Martone T, Rosso P, Albera R, Migliaretti G, Fraire F, Pignataro L, Pruneri G, Bellone G, Cortesina G (2005) Prognostic relevance of CD105+ microvessel density in HNSCC patient outcome. Oral Oncol 41:147–155

    Article  PubMed  CAS  Google Scholar 

  29. Massi D, Franchi A, Paglierani M, Ketabchi S, Borgognoni L, Reali UM, Santucci M (2004) Vasculogenic mimicry has no prognostic significance in pT3 and pT4 cutaneous melanoma. Hum Pathol 35:496–502

    Article  PubMed  CAS  Google Scholar 

  30. Mineo TC, Ambrogi V, Baldi A, Rabitti C, Bollero P, Vincenzi B, Tonini G (2004) Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumour vessel invasion after radical surgery for IB-IIA non-small cell lung cancer. J Clin Pathol 57:5917

    Article  CAS  Google Scholar 

  31. Nagatsuka H, Hibi K, Gunduz M, Tsujigiwa H, Tamamura R, Sugahara T, Sasaki A, Nagai N (2005) Various immunostaining patterns of CD31, CD34 and endoglin and their relationship with lymph node metastasis in oral squamous cell carcinomas. J Oral Pathol Med 34:70–76

    Article  PubMed  Google Scholar 

  32. Pazouki S, Chisholm DM, Adi MM, Carmichael G, Farquharson M, Ogden GR, Schor SL, Schor AM (1997) The association between tumour progression and vascularity in the oral mucosa. J Pathol 183:39–43

    Article  PubMed  CAS  Google Scholar 

  33. Pfister DG, Ang K, Brockstein B, Colevas AD, Ellenhorn J, Goepfert H, Hicks WL Jr, Hong WK, Kies MS, Lydiatt W, McCaffrey T, Mittal BB, Ridge JA, Schuller DE, Shah JP, Spencer S, Trotti A 3rd, Urba S, Weymuller EA Jr, Wheeler RH 3rd, Wolf GT; National Comprehensive Cancer Network (2000) NCCN practice guidelines for head and neck cancers. Oncology (Huntingt) 14:163–194

    CAS  Google Scholar 

  34. Reinmuth N, Parikh AA, Ahmad SA, Liu W, Stoeltzing O, Fan F, Takeda A, Akagi M, Ellis LM (2003) Biology of angiogenesis in tumors of the gastrointestinal tract. Microsc Res Tech 60:199–207

    Article  PubMed  CAS  Google Scholar 

  35. Saad RS, Jasnosz KM, Tung MY, Silverman JF (2003) Endoglin (CD105) expression in endometrial carcinoma. Int J Gynecol Pathol 22:248–253

    Article  PubMed  Google Scholar 

  36. Saad RS, Liu YL, Nathan G, Celebrezze J, Medich D, Silverman JF (2004) Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer. Mod Pathol 17:197–203

    Article  PubMed  CAS  Google Scholar 

  37. Salven P, Heikkila P, Anttonen A, Kajanti M, Joesuu H (1997) Vascular endothelial growth factor in squamous cell head and neck carcinoma: expression and prognostic significance. Mod Pathol 10:1128–1133

    PubMed  CAS  Google Scholar 

  38. Salvesen HB, Gulluoglu MG, Stefansson I, Akslen LA (2003) Significance of CD 105 expression for tumour angiogenesis and prognosis in endometrial carcinomas. APMIS 111:1011–1018

    Article  PubMed  Google Scholar 

  39. Schimming R, Marme D (2002) Endoglin (CD105) expression in squamous cell carcinoma of the oral cavity. Head Neck 24:151–156

    Article  PubMed  Google Scholar 

  40. Tanaka F, Otake Y, Yanagihara K, Kawano Y, Miyahara R, Li M, Yamada T, Hanaoka N, Inui K, Wada H (2001) Evaluation of angiogenesis in non-small cell lung cancer: comparison between anti-CD34 antibody and anti-CD105 antibody. Clin Cancer Res 7:3410–3415

    PubMed  CAS  Google Scholar 

  41. Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP, Gion M, Belien JA, de Waal RM, Van Marck E, Magnani E, Weidner N, Harris AL, Dirix LY (2002) Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer 38:1564–1579

    Article  PubMed  CAS  Google Scholar 

  42. Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma. N Engl J Med 324:1–8

    Article  PubMed  CAS  Google Scholar 

  43. Wang JM, Kumar S, Pye D, Haboubi N, al-Nakib L (1994) Breast carcinoma: comparative study of tumor vasculature using two endothelial cell markers. J Natl Cancer Inst 86:386–388

    Article  PubMed  CAS  Google Scholar 

  44. Yagasaki H, Kawata N, Takimoto Y, Nemoto N (2003) Histopathological analysis of angiogenic factors in renal cell carcinoma. Int J Urol 10:220–227

    Article  PubMed  Google Scholar 

  45. Yu JX, Zhang XT, Liao YQ, Zhang QY, Chen H, Lin M, Kumar S (2003) Relationship between expression of CD105 and growth factors in malignant tumors of gastrointestinal tract and its significance. World J Gastroenterol 9:2866–2869

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, University of Ioannina Medical School, 45110, Ioannina, Greece

    Panayiotis A. Kyzas, Niki J. Agnantis & Dimitrios Stefanou

Authors
  1. Panayiotis A. Kyzas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Niki J. Agnantis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dimitrios Stefanou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Panayiotis A. Kyzas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kyzas, P.A., Agnantis, N.J. & Stefanou, D. Endoglin (CD105) as a prognostic factor in head and neck squamous cell carcinoma. Virchows Arch 448, 768–775 (2006). https://doi.org/10.1007/s00428-006-0195-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-006-0195-4

Keywords

Search

Navigation