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Angiogenic switch during tumor progression of carcinoma ex-pleomorphic adenoma

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Abstract

We analyzed the tumor vascularization in carcinomas ex-pleomorphic adenoma (CXPA) to investigate the angiogenic switch during the malignant transformation of pleomorphic adenoma (PA) to carcinoma and during tumor progression. In eight cases of early CXPA (intracapsular and minimally invasive tumors), eight of advanced CXPA (widely invasive tumors), and ten of PA without malignant transformation, tumor vascularization was assessed in histological samples by measuring total microvascular area (TVA) and microvessel density (MVD) using CD34 and CD105 antibodies. MVD for CD105 increased significantly during tumor progression, whereas this was not the case for CD34 MVD. Comparing widely invasive CXPA with and without myoepithelial differentiation, CXPA with myoepithelial differentiation showed a significantly lower number of CD105 positive vessels but revealed higher TVA values. In these tumors, the neoplastic cells usually formed larger hypovascularized aggregates that were often surrounded by large-sized vessels. In conclusion, the antibody CD105 reveals an angiogenic switch during the progression from adenoma to carcinoma in salivary glands. The degree of angiogenesis and the total vascular area have distinctive patterns in CXPA with and without myoepithelial differentiation. Low angiogenesis associated with high TVA value is more characteristic of CXPA with myoepithelial differentiation.

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References

  1. Akagi K, Ikeda Y, Sumiyoshi Y, Kimura Y, Kinoshita J, Miyazaki M, Abe T (2002) Estimation of angiogenesis with anti-CD105 immunostaining in the process of colorectal cancer development. Surgery 131:109–113

    Article  Google Scholar 

  2. Altemani A, Martins MT, Freitas L, Soares F, Araújo NS, Araújo VC (2005) Carcinoma ex pleomorphic adenoma (CXPA): immunoprofile of the cells involved in carcinomatous progression. Histopathology 46:635–641

    Article  PubMed  CAS  Google Scholar 

  3. Ding S, Li C, Lin S, Yang Y, Liu D, Han Y, Zhang Y, Li L, Zhou L, Kumar S (2006) Comparative evaluation of microvessel density determined by CD34 or CD105 in benign and malignant gastric lesion. Human Pathol 37:861–866

    Article  CAS  Google Scholar 

  4. Diodoro MG, Di Carlo E, Zappacosta R, Iezzi M, Coletti A, Modesti A, D’Antuono T, Forni G, Musiani P (2000) Salivary carcinoma in HER-2/neu transgenic male mice: an angiogenic switch is not required for tumor onset and progression. Int J Cancer 88:329–335

    Article  PubMed  CAS  Google Scholar 

  5. Doi R, Kuratate I, Okamoto E, Ryoke K, Ito H (1999) Expression of p53 oncoprotein increase intratumoral microvessel formation in human salivary gland carcinomas. J Oral Pathol Med 28:259–263

    Article  PubMed  CAS  Google Scholar 

  6. Duff SE, Li C, Garland JM, Kumar S (2003) CD105 is important for angiogenesis: evidence and potential applications. FASEB J 17:948–992

    Article  Google Scholar 

  7. Ellis GL, Auclair PL (1996) Malignant epithelial tumors. In: Rosai J, Sobin LH (eds) Atlas of tumor pathology, series 3, section 5, fascicle 17. Armed Forces Institute of Pathology, Washington, DC, pp 155–373

    Google Scholar 

  8. Fonsatti E, Sigalotti L, Arslan P, Altomonte M, Maio M (2003) Emerging role of endoglin (CD105) as a marker of angiogenesis with clinical potential in human malignancies. Curr Cancer Drug Targets 3:427–432

    Article  PubMed  CAS  Google Scholar 

  9. Fox SB, Harris AL (2004) Histological quantitation of tumour angiogenesis. APMIS 112:413–430

    Article  PubMed  Google Scholar 

  10. Gnepp DR (1993) Malignant mixed tumors of the salivary:glands a review. Pathol Annu 28:279–328

    PubMed  Google Scholar 

  11. Gnepp DR, Brandwein MS, Henley JD (2000) Salivary and lacrimal glands. In: Gnepp DR (ed) Diagnostic surgical pathology of the head and neck. W.B. Saunders, Philadelphia, pp 325–430

    Google Scholar 

  12. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  PubMed  CAS  Google Scholar 

  13. Hlatky L, Hahnfeldt P, Folkman J (2002) Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn’t tell us. J Natl Cancer Inst 94:883–893

    PubMed  Google Scholar 

  14. Korkolopoulou P, Konstantinidou AE, Kavantzas N, Patsouris E, Pavlopoulos PM, Christodoulou P, Thomas-Tsagli E, Davaris P (2001) Morphometric microvascular characteristics predict prognosis in superficial and invasive bladder cancer. Virchows Arch 438:6036–6611

    Article  CAS  Google Scholar 

  15. Korkolopoulou P, Patsouris E, Kavantzas N, Konstantinidou AE, Christodoulou P, Thomas-Tsagli E, Pananikolaou A, Eftychiadis C, Pavlopoulos PM, Angelidakis D, Rologis D, Davaris P (2002) Prognostic implications of microvessel morphometry in diffuse astrocytic neoplasms. Neuropathol Appl Neurobiol 28:57–66

    Article  PubMed  CAS  Google Scholar 

  16. Laitakari J, Nayha V, Stenback F (2004) Size, shape, structure, and direction of angiogenesis in laryngeal tumour development. J Clin Pathol 57:394–401

    Article  PubMed  CAS  Google Scholar 

  17. Lewis JE, Olsen KD, Sebo TJ (2001) Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. Hum Pathol 32:596–604

    Article  PubMed  CAS  Google Scholar 

  18. Livolsi VA, Perzin KH (1977) Malignant mixed tumors arising in salivary glands. I. Carcinomas arising in benign mixed tumors: a clinicopathologic study. Cancer 39:2209–2230

    Article  PubMed  CAS  Google Scholar 

  19. Minhajat R, Mori D, Yamasaki F, Sugita Y, Satoh T, Tokunaga O (2006) Endoglin (CD105) expression in angiogenesis of colon cancer: analysis using tissue microarrays and comparison with other endothelial markers. Virchows Arch 44:127–134

    Article  CAS  Google Scholar 

  20. Nathonson SD (2003) Insights into the mechanisms of lymph node metastasis. Cancer 98:413–423

    Article  Google Scholar 

  21. Nguyen M, Lee MC, Wang JL, Tomlinson JS, Shao ZM, Alpaugh ML, Barsky SH (2000) The human myopithelial cell displays a multifaceted anti-angoigenic phenotype. Oncogene 19:3449–3459

    Article  PubMed  CAS  Google Scholar 

  22. Pezzella F, Pastorino U, Tagliabue E, Andreola S, Sozzi G, Gasparini G, Menard S, Gatter KC, Harris AL, Fox S, Buyse M, Pilotti S, Pierotti M, Rilke F (1997) Non-small-cell lung carcinoma tumor growth without morphological evidence of neo-angiogenesis. Am J Pathol 1:1417–1423

    Google Scholar 

  23. Sabattini E, Bisgaard K, Ascani S, Poggi S, Piccioli M, Ceccarelli C, Pieri F, Fraternali-Orcioni G, Pileri SA (1998) The EnVision™+ system: a new immunohistochemical method for diagnostics and research. Critical comparison with the APAAP, ChemMate™, CSA, LABC and SABC techniques. J Clin Pathol 51:506–511

    Article  PubMed  CAS  Google Scholar 

  24. Sharma S, Sharma MC, Sarkar C (2005) Morphology of angiogenesis in human cancer: a conceptual overview, histoprognostic perspective and significance of neoangiogenesis. Histopathology 46:481–489

    Article  PubMed  CAS  Google Scholar 

  25. Sternlicht MD, Barsky SH (1997) The myoepithelial defense: a host defense against cancer. Med Hypotheses 48:37–46

    Article  PubMed  CAS  Google Scholar 

  26. Swelam W, Ida-Yonemochi H, Maruyama S, Ohshiro K, Cheng J, Saku T (2005) Vascular endothelial growth factor in salivary pleomorphic adenomas: one of the reasons for their poorly vascularized stroma. Virchows Arch 446:653–662

    Article  PubMed  CAS  Google Scholar 

  27. Tanaka F, Otake Y, Yanagihara K, kawano Y, Miyahara R, Li M, Ishikawa S, Wada H (2003) Correlation between apoptotic index and angiogenesis in non-small cell lung cancer: comparison between CD105 and CD34 as a marker of angiogenesis. Lung Cancer 39:289–296

    Article  PubMed  Google Scholar 

  28. 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 

  29. Wang JM, Kumar S, Pye D, van Agthoven AJ, Krupinski J, Hunter RD (1993) A monoclonal antibody detects heterogeneity in vascular endothelium of tumours and normal tissues. Int J Cancer 54:363–370

    Article  PubMed  CAS  Google Scholar 

  30. Zhang J, Peng B, Chen X (2005) Expressions of nuclear factor kappa B, inducible nitric oxide synthase, and vascular endothelial growth factor in adenoid cystic carcinoma of salivary glands: correlations with the angiogenesis and clinical outcome. Clin Cancer Res 11:7334–7743

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) for supporting this study (grant number 04/07960-0). K Metze receives a grant as senior researcher of the National Research Council (CNPq; grant number 304358/2004-5). This paper was supported by FAPESP grant number 04/07960-0 and CNPq number 304358/2004-5.

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Correspondence to A. Altemani.

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Soares, A.B., Juliano, P.B., Araujo, V.C. et al. Angiogenic switch during tumor progression of carcinoma ex-pleomorphic adenoma. Virchows Arch 451, 65–71 (2007). https://doi.org/10.1007/s00428-007-0438-z

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  • DOI: https://doi.org/10.1007/s00428-007-0438-z

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