Immunohistochemical expression of pericytes and myofibroblasts in the extracellular matrix of oral actinic cheilitis and squamous cell carcinoma: a comparative study

Authors

  • Flávia Godinho Wanderley Bahiana School of Medicine and Public Health
  • Carlla Silva Nunes Bahiana School of Medicine and Public Health
  • Maira Sá Ferreira Bahiana School of Medicine and Public Health
  • Ana Cristina Gonzalez Bahiana School of Medicine and Public Health
  • Silvia Regina Almeida Reis Bahiana School of Medicine and Public Health
  • Alena Ribeiro Alves Peixoto Medrado Bahiana School of Medicine and Public Health

DOI:

https://doi.org/10.15448/1980-6523.2017.1.23344

Keywords:

Carcinoma, Pericytes, Myofibroblasts

Abstract

OBJECTIVE: The aim of the present study is to conduct a comparative analysis of oral actinic cheilitis and squamous cell carcinomas by immunohistochemical analysis.
METHODS: This cross-sectional study utilizes a convenience sample obtained from the archives of an oral pathology laboratory from a higher education institution. Tissue sections from patients diagnosed with actinic cheilitis and carcinoma were immunohistochemically analyzed using monoclonal antibodies specific for smooth muscle alpha actin (SMA) and neuron-glial antigen 2 (NG2). Individual cells that stained positive for these proteins were counted in specific fields by means of histomorphometry.
RESULTS: Subsequent statistical analysis revealed a higher number of NG2-positive when compared with SMA-positive cells in both lesion types (p = 0.005) and these cells were located adjacent to blood vessels. The differences between normal oral mucosa, severe dysplasia, and carcinoma specimens were statistically significant (p = 0.009; p = 0.006).
CONCLUSION: These data strongly suggest that increased expression of NG2- and SMA-positive cells is associated with formation of blood capillaries, highlighting the importance of angiogenesis in tumor progression.

References

Vieira RA, Minicucci EM, Marques ME, Marques SA. Actinic cheilitis and squamous cell carcinoma of the lip: clinical, histopathological and immunogenetic aspects. An Bras Dermatol 2012;87(1):105–14.https://doi.org/10.1590/S0365-05962012000100013

Ribeiro CF, Souza FH, Jordão JM, Haendchen LC, Mesquita L, Schmitt JV, et al. Photodynamic therapy in actinic cheilitis: clinical and anatomopathological evaluation of 19 patients. An Bras Dermatol 2012;87(3):418-23. https://doi.org/10.1590/S0365-05962012000300011

Gomes AP, Johann JE, Lovato GG, Ferreira AM. Comparative analysis of the mast cell density in normal oral mucosa, actinic cheilitis and lip squamous cell carcinoma. Braz Dent J 2008;19(3):186-9. https://doi.org/10.1590/S0103-64402008000300002

Banoczy J, Csiba A. Occurrence of epithelial dysplasia in oral leukoplakia. Analysis and follow-up study of 12 cases.Oral Surg 1976;42(6):766-74. https://doi.org/10.1016/0030-4220(76)90099-2

Costa NL, Leite AFO, Junior APC, Alencar RCG, Bittar GOJ, Silva TA,

Batista AC. Density and migration of mast cells in lip squamous cell

carcinoma and actinic cheilitis. Histol Histopathol 2009;24(4):457-65.

Xian X, Håkansson J, Ståhlberg A, Lindblom P, Betsholtz C, Gerhardt H, Semb H. Pericytes limit tumor cell metastasis. J Clin Invest 2006;116(3):642-51. https://doi.org/10.1172/JCI25705

Medrado A, Costa T, Prado T, Reis S, Andrade Z.Phenotype characterization of pericytes during tissue repair following low-level laser therapy. Photodermatol, Photoimmunol Photomed2010;26(4):192-7.https://doi.org/10.1111/j.1600-0781.2010.00521.x

Cataldo E, Doku HC. Solar cheilitis. J Dermatol Surg Oncol. 1981; 7(12):989-95. https://doi.org/10.1111/j.1524-4725.1981.tb00203.x

Von Tell D, Armulik A, Betsholtz C.Pericytes and vascular stability.Exp Cell Res 2006;312(5):623-9. https://doi.org/10.1016/j.yexcr.2005.10.019

Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G. The myofibroblast. Am J Pathol 2007;170(6):1807-16. https://doi.org/10.2353/ajpath.2007.070112

Kramer IR, Lucas RB, Pindborg JJ, Sobin LH. Definition of Leukoplakia and related lesions: an aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol 1978;46(4):518-39. https://doi.org/10.1016/0030-4220(78)90383-3

Barnes L, Eveson, JW, Reichart P, Sidransky D. World Health Organization classification of tumours. Pathology and Genetics of Head and Neck Tumours. IARC Press: Lyon; 2005.

Martins-Filho PR, Da Silva LC, Piva MR.The prevalence of actinic cheilitis in farmers in a semi-arid northeastern region of Brazil.Int J Dermatol 2011;50(9):1109-14. https://doi.org/10.1111/j.1365-4632.2010.04802.x

Lucena EES, Costa DCB, Silveira EJD3, Lima KC. Prevalence and factors associated to actinic cheilitis in beach workers. Oral Dis 2012;18(6):575-9.https://doi.org/10.1111/j.1601-0825.2012.01910.x

Sarmento DJS, Miguel MCC, Queiroz LMG, GP Godoy, da Silveira EJD. Actinic cheilitis: clinicopathologic profile and association with degree of dysplasia. Int J Dermatol 2014;53(4):466-72. https://doi.org/10.1111/ijd.12332

Pires FR, Bueno RH, Alves FA, Almeida OP. Queilite actínica: aspectos clínicos e preventivos. Rev Assoc Paul Cir Dent 2001;55(3):200-3.

Piñera-Marques K, Lorenço SV, Silva LFF, Sotto MN, Carneiro PC.

Actinic lesions in fishermen´s lower lip: clinical, cytopathological and histopathologic analysis. Clinics 2010;65(4):363-7. https://doi.org/10.1590/S1807-59322010000400003

Lúcio PS, Cavalcanti AL, Alves PM, Godoy GP, Nonaka CF. Myofibroblasts and their relationship with oral squamous cell carcinoma. Braz J Otorhinolaryngol 2013;79(1):112-8. https://doi.org/10.5935/1808-8694.20130019

Margaritescu C, Simionescu C, Pirici D, Mogoanta L, Ciurea R, Stepan A. Immunohistochemical characterization of tumoral vessels in oral squamous cell carcinoma. RJME 2008;49(4):447-58.

Araújo CP, Xavier FCA, Gurgel CAS, Ramos EAG, Freitas VS, Schlaepfer- Sales CB, et al. Elastin accumulation in actinic cheilitis with different degrees of epithelial dysplasia. Int J Morphol 2012;30(2):627-33. https://doi.org/10.4067/S0717-95022012000200044

De Freitas MCA, Ramalho LMP, Xavier FCA, Moreira ALG, Reis SRA. p53 and MDM2 protein expression in actinic cheilitis. J Appl Oral Sci 2008;16(6):414-9. https://doi.org/10.1590/S167877572008000600011

Beltrami CA, Desinan L, Rubini C. Prognostic factors in squamous cell carcinoma of the oral cavity. A retrospective study of 80 cases. Pathol Res Pract 1992;188(4-5):510-6. https://doi.org/10.1016/S0344-0338(11) 80047-6

Kellermann MG, Sobral LM, da Silva SD, Zecchin KG, Graner E, Lopes MA, et al. Myofibroblasts in the stroma of oral squamous cell carcinoma are associated with poor prognosis. Histopathol 2007;51(6):849-53. https://doi.org/10.1111/j.1365-2559.2007.02873.x

Schürch W, Seemayer TA, Lagacé R. Stromal myofibroblasts in primary invasive and metastatic carcinomas. A combined immunological, light and electron microscopic study. Virchows Arch A Pathol Anat Histol 1981;391(2):125-39. https://doi.org/10.1007/BF00437591

Daly AJ, McIlreavey L, Irwin CR. Regulation of HGF and SDF-1 expression by oral fibroblasts – implications for invasion of oral cancer. Oral Oncol 2008;44(7):646-51. https://doi.org/10.1016/j.oraloncology.2007.08.012

Nielsen JD, Moeslund M, Wandall HH, Dabelsteen S. Influences of tumor stroma on the malignant phenotype. J Oral Pathol Med 2008;37(7):412-6. https://doi.org/10.1111/j.1600-0714.2008.00655.x

Martins GB, Ribeiro MB, Reis SRA. Análise de miofibroblastos no estroma de carcinoma epidermoide da boca. Rev pós-grad 2011;18(4):244-52.

Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol 2002;29(6 Suppl 16):15-8. https://doi.org/10.1016/S0093-7754(02)70065-1

Crocker DJ, Murad TM, Geer JC. Role of the pericyte in wound healing. An ultrastructural study. Exp Mol Pathol 1970;13(1):51-65. https://doi.org/10.1016/0014-4800(70)90084-5

Takakura N. Role of hematopoietic lineage cells as accessory components in blood vessel formation. Cancer Sci 2006;97(7):568-74. https://doi.org/10.1111/j.1349-7006.2006.00223.x

Farrington-Rock C, Crofts NJ, Doherty MJ, Ashton BA, Griffin-Jones C, Canfield AE. Chondrogenic and adipogenic potential of microvascular pericytes. Circulation 2004;110(15):2226-32. https://doi.org/10.1161/01.CIR.0000144457.55518.E5

Sridhara SU, Choudaha N, Kasetty S, Joshi PS, Kallianpur S, Tijare M. Stromal myofibroblasts in nonmetastatic and metastatic oral squamous cell carcinoma: An immunohistochemical study. J Oral Maxillofac Pathol 2013;17(2):190-4. https://doi.org/10.4103/0973-029X.119758

Ozerdem U, Stallcup WB. Early contribution of pericytes to angiogenic sprouting and tube formation.Angiogenesis 2003;6(3):241-9. https://doi.org/10.1023/B:AGEN.0000021401.58039.a9

Crocker DJ, Murad TM, Geer JC. Role of the pericyte in wound healing. An ultrastructural study. Exp Mol Pathol 1970;13(1):51-65. https://doi.org/10.1016/0014-4800(70)90084-5

Takakura N. Role of hematopoietic lineage cells as accessory components in blood vessel formation. Cancer Sci 2006;97(7):568-74. https://doi.org/10.1111/j.1349-7006.2006.00223.x

Farrington-Rock C, Crofts NJ, Doherty MJ, Ashton BA, Griffin-Jones C, Canfield AE. Chondrogenic and adipogenic potential of microvascular pericytes. Circulation 2004;110(15):2226-32. https://doi.org/10.1161/01.CIR.0000144457.55518.E5

Sridhara SU, Choudaha N, Kasetty S, Joshi PS, Kallianpur S, Tijare M. Stromal myofibroblasts in nonmetastatic and metastatic oral squamous cell carcinoma: An immunohistochemical study. J Oral Maxillofac Pathol 2013;17(2):190-4. https://doi.org/10.4103/0973-029X.119758

Ozerdem U, Stallcup WB. Early contribution of pericytes to angiogenic sprouting and tube formation.Angiogenesis 2003;6(3):241-9. https://doi.org/10.1023/B:AGEN.0000021401.58039.a9

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Published

2017-10-03

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