Correlation Between Microvessel Density and Morphological Features in Skin Squamous Cell Carcinoma

Open access


Introduction. Abnormal angiogenesis is described in tumor growth and it facilitates its metastatic spread. Tumors with high angiogenic activity belong to the category of aggressive tumors with poor prognosis for patients.

The aim of this study was to determine the blood vessels density (BVD), i.e. neovascularization at the tumor invasive front in skin squamous cell carcinoma (SCC) in order to determine its possible role in the tumor progression, and to correlate it to the blood vessels density of healthy skin and with the prognostic parameters of the TNM classification: T status, depth of tumor invasion (DI) and tumor histological grade (G), which were also correlated between each other.

Material and Methods. The material consisted of surgical specimens obtained from 30 patients with skin SCC, who underwent surgery.

Tissue samples were routinely processed by standard paraffin technique stained by Hematoxilin-Eosin and immunohistochemically with antibodies against smooth muscle actin (SMA) and CD34. The BVD in the invasive front of the neoplasms was correlated to the healthy skin, tumor status (pT), depth of invasion and grade of histological differentiation (pG).

Results. The histological analysis has shown a high statistical difference in the density of blood vessels in SCC compared to the healthy skin and statistical difference in BVD in neoplasms with different depth of invasion and different grade of differentiation. The density of neovascularzation increased with the deeper invasion and the worse differentiation.

Conclusion. The increased vascularization at the invasive front of SCC with deeper invasion and worse differentiation has pointed out to its possible role in neoplasm progression.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Gijatromanolaki A Sivridis E Koukourakis M.Tumour angiogenesis:vascular growth and survival. APMIS. 2004;112:431-440.

  • 2. Rowe DE Carroll RJ Day CL. Prognostic factors for local recurrence metastasis and survival rates in squamous cell carcinoma of the skin ear and lip. J Am Acad Dermatol 1992;26(6):976-990.

  • 3. Sharma S Sharma MC Sarcar C. Morphology of angiogenesis in human cancer: a conceptual overview histoprognostic perspective and significance of neoangiogenesis. Histopathology 2005;46:481-489.

  • 4. Larsen M Artym VV Green JA Yamada KM. The matrix reorganized:extracellular matrix remodeling and integrin signaling. Curr Opin Cell Biol 2006;18:463-471.

  • 5. Kerbel RS. Tumor angiogenesis. N Engl J Med 2008; 358:2039-49.

  • 6. Auguste P Lemiere S Lahargue FL Bikfalvi A. Molecular mechanisms of tumor vascularization. Crit Rev Oncol Hematol 2004;54:53-63.

  • 7. Lamalice L Le Boeuf F Huot J. Endotelial cell migration during angiogenesis. Cirk Res 2007;100:782-794.

  • 8. Gerhart H Betsholtz CH. Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 2003;314:15-23.

  • 9. Bremnes RM Donnem T Al-Said S Al-Shibly K Andersen S Sirera R Camps C Marinez I Busund LT. The role of tumor stroma in cancer progresion and prognosis. J Thorac Oncol 2011;6:209-217.

  • 10. Verdolini R Amerio P Goteri G Bugatti L Lucarini G Mannello B Filosa G Offidani A Brancorsini D Biagini G Giangiacomi M. Cutaneous carcinomas and preinvasive neoplastic lesions. Role of MMP-2 and MMP-9 metalloproteinases in neoplastic invasion and their relationship with proliferative activity and p53 expression. J Cutan Pathol 2001; 28: 120-126.

  • 11. Kyzas PA Stefanou D Batistatou A Agnantis NJ.Potential autocrine function of vascular endothelial growth factor in head and neck cancer via vascular endothelial growth factor receptor-2. Mod Pathol 2005;18:485-494.

  • 12. Florence MEB Massuda JY Bröcker EB Metze K Cintra ML De Souza EM. Angiogenesis in the progression of cutaneous squamous cell carcinoma: an immunohistochemical study of endothelial markers. Clinics (SaoPaolo) 2011;66(3):465-468.

  • 13. Shieh YS Lee HS Shieh SGChu YW Wu CWChang LC. Role of angiogenic and non-angiogenic mechanisms in oral squamous cell carcinoma: correlation with histological differentiation and tumor progression. J Oral Pathol Med 2004;33(10):601-6.

  • 14. Edge SB. Byrd DR. Compton CC. Fritz AG. Greene FI. Trotti A. Cancer staging handbook: from the AJCC cancer stading manual AJCC editors 7th edition. Springer New York: 2010 p.359-375.

  • 15. Velasco P Lange-Asschenfeldt B. Dermatological aspects of angiogenesis. Br J Dermatol 2002; 147:841-852.

  • 16. Bergers G Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer 2003;3:401-410.

  • 17. Yorioka CW Coletta RD Alves F Nishimoto IN Kowalski LP Graner E. Matrix metalloproteinase-2 and -9activities correlate with the disease- free survival of oral squamous cell carcinoma patients. Int J Oncol 2002; 20(1):189-194.

  • 18. Folkman J. Role of angiogenesisin tumor growth and metastasis. Semin Oncol 2002; 29(16):15-8.

  • 19. Folkman J.Fundamental concepts of the angiogenetic process. Curr Mol Med.2003;3:643-651.

  • 20. Folkman JKalluri R. Tumor angiogenesis.In: Kufe DW. Pollock RE Weichselbaum RR Bast RC Gansler TS Holland JF Frei E editors. Cancer Medicine 6th edition.Hamilton:BC Decker 2003.

  • 21. Folkman J. Angiogenesis. Annu Rev Med 2006;57:1-18.

  • 22. Ribatti D. Judah Folkman a pioneer in the studу of angiogenesis. Angiogenesis 2008:11:3-10.

  • 23. Raica M Cimpean AM Ribatti D. Angiogenesis in pre-malignat conditions. Eur J Cancer2009; 45:1924-1934.

  • 24. Abulafia O Triest We Sherer DM. Angiogenesis in squamous cell carcinoma in situ and microinvasive carcinoma of the uterine cervix. Obset Gynecol 1996;88(6):927-32.

  • 25. Gijatromanolaki A Koukourakis M Sivridis E Thore PHE Brekken RA Konstantinos S Fountzilas G Gatter KC Haris AL. Tumor specific activation of the VEGF/KDR angiogenic pathway in a subset of locally advanced cell head and neck carcinomas. Clin Exp Metastasis 2000;18:313-319.

  • 26. Sridhara SU Choudaha N Kasetty S Joshi PS Kalianpur S Tijare M. Stromal myofibroblasts in nonmetastatic and metastatic oral squamous cell carcinoma: An immunohistochemical study. J Oral Maxillofac Pathol 2013;17(2):190-194.

  • 27. Yan W Wistuba II Emmert-buck RM Erickson SH. Squamous cell carcinoma-similarities and differences among anatomical sites. Am J Cancer Res 2011; 1(3):275-300

  • 28. Winter J Kneitz H Brocker EB. Blood vessel density in basal cell carcinomas and benign trichogenic tumors as a marker for differential diagnosis in dermatopathology. J Skin Cancer 2011Artical ID2413825 pages

  • 29. Staibano S Boscaino A Salvatore G Orabona P Palomini I De Rosa G. The prognostic significance of tumor angiogenesis in nonaggressive and aggressive basal cell carcinoma of the human skin. Hum Pathol1996;27(7):695-700.

  • 30. Loggini B Boldrini L Gisfredi S Ursino S Camacci T De Jeso K Cervadoro G Pingitore R Barachini P Leocata P Fontanini G. CD34 microvessel density and VEGF expression in basal and squamous cell carcinoma. Pathol Res Pract 2003;199(11):705-712

  • 31. Kacar A Arikok AT Kokenek Unal TD Onder E Hucumenoglu S Alper M. Stromal expression of CD34 α-smooth muscle actin and CD26/ DPPIV in squamous cell carcinoma of the skin: a comparative immunohistochemical study. Pathol Oncol Res 2012;18(1):25-31.

  • 32. Fina L Molgaard HV Robertson D Bradley NJ Monaghan P Delia D Sudherland DR Baker MA Greaves MF. Expression of the CD34 gene in vascular endothelial cells.Blood 1990;75(12):2417-2426.

  • 33. Ascani G Balercia P Messi M Lupi L Goteri G Filosa A Stramazzotti D Pieramici T Rubini C. Angiogenesis in oral squamous cell carcinoma. Acta Otorhinolaryngol Ital 2005;25(1)13-17.

  • 34. Shivamallappa SM Venkatraman NT Shreedhar B Mohanty L Shenoy S. Role of angiogenesis in oral squamous cell carcinoma development and metastasis: an immunohistochemical study. Int J Oral Sci 2011;3(4):216-224.

  • 35. Zatterstrom UK Brun E Willen R Kjellen E Wennerberg J. Tumor angiogenesis and prognosis in squamous cell carcinoma of the head and neck. Head Neck 1995;17(4): 312-318

  • 36. Weidner N. Intratumoral microvassel density as a prognostic factor in cancer. Am J Pathol 1995;147(1):9-19.

  • 37. Vermeulen PB Gasarini G Fox SB Toi M Martin M McCulloch P Pezzella F Viale G Weidner N Harris AL Ditrix Y. Quantification of angiogenesis in solid human tumors: an international consensus on the methodology and criteria of evaluation. Eur J Cancer 1996;32A(14):2474-2484.

  • 38. Breuninger H Black B Rassner G. Microstaging of squamous cell carcinomas.Am J Clin Pathol 1990;94(5):624-7.

  • 39. Broders AC. Practical points on the microscopic grading of carcinoma. N Y State J Med. 1932; 32: 667-671.

  • 40. Strieth S Hartschuh W Pilz L Fusening NE. Angiogenic switch occurs late in squamous cell carcinomas of human skin. Br J Cancer 2000; 82(3):591-600.

  • 41. Nico B BenagianoV Mangieri D Maruotti N Vacca A Ribatti D. Еvaluation of microvascular density in tumors: pro and contra. Histol Histopathol 2008; 23: 601-607

  • 42. Fox SB Harris AL. Histological quantitation of tumor angiogenesis. APMIS 2004;112:413-30.

  • 43. WeidnerN. Measuring intratumoral microvassel density.Methods Enzymol 2008;444:305-23.

  • 44. Tan WJ Chia CS Tan HK Soo KC Iyer NG. Prognostic significance of invasion depth in oral tongue squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec 2012;74(5):264-70.

  • 45. Emerson RE Ulbright TM Eble JN Geary WA Eckert GJ Cheng L. Predicting cancer progression in patients with penile squamous cell carcinoma: The importance of depth of invasion and vascular invasion. Mod Pathol 2001;14(10):963-968.

  • 46. Kristensen GB Abeler VM Risberg B Tropé C Bryne M. Tumor size depth of invasion and grading of the invasive tumor front are the main prognostic factors in early squamous cell cervical carcinoma. Gynecol Oncol 1999;74(2):245-251.

Journal information
Impact Factor
CiteScore 2017: 0.45

SCImago Journal Rank (SJR) 2018: 0.177

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 248 182 13
PDF Downloads 122 105 5