CORRELATION BETWEEN MICROVESSEL DENSITY AND MORPHOLOGICAL FEATURES IN SKIN SQUAMOUS CELL CARCINOMA
Keywords:
squamous cell carcinoma, CD34, neovascularization, histological differentiationAbstract
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 a poor prognosis for patients.
The aim of this study was to determine neovascularization at the invasive front of the tumor stroma in skin squamous cell carcinoma (SCC) in relation to the healthy skin and the ratio of blood vessel density in the skin SCC with a different depth of invasion and different degree of histological differentiation.
Materials and methods: The material consisted of surgical specimens obtained from 30 patients with skin SCC, who underwent surgery at the University Clinic for Plastic and Reconstructive Surgery and University Clinic for Maxillofacial Surgery. Samples were analyzed by standard paraffin technique stained by hematoxylin-eosin and immunohistochemically with antibodies against smooth muscle actin (SMA) and CD34.
Results: The difference found in the neovascularization density in neoplasms with different degree of differentiation (G1, G2, G3) was statistically significant. The differences in the depth of stromal invasion in skin SCC registered in neoplasms with different degree of histological differentiation (G) showed a statistical significance for G1, G2, G3. The density of neovascularization in skin SCC was in a positive correlation with the depth of invasion.
Conclusion: The increased vascularization at the invasive front of a neoplasm in SCC with deeper invasion and higher grade has pointed out to its possible role in neoplasm progression.
References
Velasco P, Lange-Asschenfeldt B. Dermatological aspects of angiogenesis. Br J Dermatol 2002; 147(5): 841-852. doi: 10.1046/j.1365-2133.2002.05073.x. doi: 10.1046/j.1365-2133.2002.05073.x.
Bremnes RM, Donnem T, Al-Said S, Al-Shibly K, Andersen S, Sirera R, et al. The role of tumor stroma in cancer progresion and prognosis. J Thorac Oncol 2011; 6(1): 209-217. doi: 10.1097/JTO.0b013e3181f8a1bd.
Folkman J. Fundamental concepts of the angiogenetic process. Curr Mol Med 2003; 3(7): 643-651. doi: 10.2174/1566524033479465.
Folkman J, Kalluri 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.
Folkman J. Angiogenesis. Annu Rev Med 2006; 57: 1-18. doi: 10.1146/annurev.med. 57.121304.131306.
Ribatti D. Judah Folkman, a pioneer in the studу of angiogenesis. Angiogenesis 2008; 11(1): 3-10. doi: 10.1007/s10456-008-9092-6.
Kerbel RS. Tumor angiogenesis. N Engl J Med 2008; 358(19): 2039-2049. doi: 10.1056/NEJMra0706596.
Auguste P, Lemiere S, Lahargue FL, Bikfalvi A. Molecular mechanisms of tumor vascularization. Crit Rev Oncol Hematol 2004; 54: 53-63.
Lamalice L, Le Boeuf F, Huot J. Endotelial cell migration during angiogenesis. Cirk Res 2007; 100(6): 782-794. doi: 10.1161/01.RES.0000259593.07661.1e.
Gerhart H, Betsholtz CH. Endothelial–pericyte interactions in angiogenesis. Cell Tissue Res 2003; 314(1): 15-23. doi: 10.1007/s00441-003-0745-x.
Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer 2003; 3(36): 401-410. doi: 10.1038/nrc1093.
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(4): 485-494. doi: 10.1038/modpathol.3800295.
Verdolini R, Amerio P, Goteri G, Bugatti L, Lucarini G, Mannello B, et al. 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(3): 120-126. doi: 10.1034/j. 1600-0560.2001.028003120.x.
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 2011; Artical ID 241382. 5 pages doi: 10.1155/2011/241382.
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 Pathol 1996; 27(7): 695-700. doi: 10.1016/ s0046-8177(96)90400-1.
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): 927-932. doi: 10.1016/s0029-7844(96)00334-1.
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. doi: 10.1002/hed.2880170407.
Ascani G, Balercia P, Messi M, Lupi L, Goteri G, Filosa A, et al. Angiogenesis in oral squamous cell carcinoma. Acta Otorhinolaryngol Ital 2005; 25(1): 13-17. PMID: 16080310.
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. doi: 10.1590/s1807-59322011000300018.
Shieh YS, Lee HS, Shieh SG, Chu YW, Wu CW, Chang 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): 601-606. doi: 10.1111/j.1600-0714.2004.00252.x.
Raica M, Cimpean AM, Ribatti D. Angiogenesis in pre-malignat conditions. Eur J Cancer 2009; 45(11): 1924-1934. doi: 10.1016/j.ejca.2009.04.007.
Gijatromanolaki A, Koukourakis M, Sivridis E, Thore PHE, Brekken RA, Konstantinos S, et 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(4): 313-319. doi: 10.1023/a:1011083121295.
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.
Fina L, Molgaard HV, Robertson D, Bradley NJ, Monaghan P, Delia D, et al. Expression of the CD34 gene in vascular endothelial cells. Blood 1990; 75(12): 2417-2426. PMID: 1693532.
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.
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. doi: 10.4103/0973-029X.119758.
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.