Eosinofilia tecidual na região do fronte invasivo do carcinoma de células espinocelulares de boca: correlação com parâmetros clínico-patológicos
Tissue eosinophilia in invasive front of oral squamous cell carcinoma: correlation with clinicopathologic parameters
De-Paula, A.M.B.; Cardoso, S.V.; Gomez, R.S.
Rev. odontol. UNESP, vol.35, n3, p.163-169, 2006
Resumo
Introdução Tem sido reconhecido que muitos cânceres são acompanhados por um infiltrado de células inflamatórias de intensidades variáveis. Atenção tem sido direcionada para o possível papel de eosinófilos no comportamento biológico de lesões neoplásicas malignas. Objetivo Avaliar a influência da quantificação de eosinófilos localizados no infiltrado inflamatório da região do fronte invasivo de amostras de carcinoma espinocelular de boca (CEC), categorizados de acordo com o tamanho das lesões primárias; a ocorrência de metástases regionais e com a severidade morfológica da região do fronte de invasão das lesões. Material e método Amostras de 38 espécimes de CEC foram investigadas nesse estudo. O sistema de gradação de malignidades para a região do fronte invasivo empregado no estudo foi idealizado por Bryne et al.9. Para a contagem de eosinófilos, foi utilizada uma lente ocular com um retículo milimetrado de 25 pontos. Doze campos microscópicos corados em H&E foram avaliados de forma aleatória, em um aumento de 400x. Apenas as regiões localizadas no fronte invasivo de cada lesão primária e que apresentavam um evidente componente inflamatório foram selecionadas para análise. A avaliação morfométrica empregada foi baseada no método de Fisher et al.29. Resultado Concordância entre patologistas quanto a gradação da severidade morfológica do fronte de invasão revelou valores de kappa de 0,81 e 0,71 para os exames intra e interobservador, respectivamente. Foi encontrada uma menor quantificação de eosinófilos nas lesões de maiores tamanhos clínicos. Os demais resultados não demonstraram a presença de correlações estatisticamente significativas. Conclusões O tamanho clínico das lesões primárias e a ocorrência de metástases cervicais não parecem ser influenciados pela severidade da gradação morfológica da região do fronte invasivo do CEC. Uma menor quantificação de eosinófilos nas lesões de maiores tamanhos clínicos parece demonstrar uma provável ação inibitória da atividade quimiotática e, conseqüentemente, das atividades antineoplásicas realizadas pelos eosinófilos contra o crescimento de células epiteliais malignas. Estudos futuros sobre a participação de eosinófilos no processo da carcinogênese bucal e de suas citocinas produzidas propiciarão um melhor entendimento sobre o comportamento biológico do CEC.
Palavras-chave
Carcinoma espinocelular, boca, metástase, estadiamento de neoplasias
Abstract
Introduction It has been long recognized that many cancers are accompanied by infiltrates of inflammatory cells of varying intensity. Attention has been directed to the possible role of eosinophils in the biologic behavior of malignant neoplastic lesions. Objective To evaluate the influence of number of eosinophils in samples of oral squamous cell carcinoma (OSCC) with different morphological and clinical parameters. Material and method Tumor tissues of 38 cases of OSCC were investigated in this study. The malignancy grading system of tumour invasive front (Bryne et al.9) was used. An ocular grid in twelve high-power fields in each specimen of primary tumor was used in haematoxylin and eosin stained slides for eosinophils counting. These counting was made in the inflammatory infiltrated in the most invasive areas of the tumour parenchyma. The morphometric analysis employed was based in the method of Fisher et al.29. Result Agreement between pathologists for grading of invasive front showed kappa values of 0.81 and 0.71 for intra and interobserver exams, respectively. Our results did not show a statistically meaningful correlation among the clinical and morphological variables (size of the lesions, cervical metastasis and grading of tumour invasive front). It was found a statiscally meaningful association between the eosinophils counting was statistically associated to the size of the lesions. It was found the smaller number of eosinophils counts in the bigger size lesions (T3/T4). Conclusions Clinical size of the lesions and cervical metastasis of the OSCC do not seem to be directly influenced by morphological grading of the tumour invasive front. A smaller eosinophils counting in bigger size lesions may demonstrate an inhibitory action of the chemotactic activity and/or their antineoplastic activities. Futures advances in the understanding of molecular control of these cells and its citokynes produced may bring a better understanding of biologic behavior of the OSCC.
Keywords
Squamous cell carcinoma, oral cavity, eosinophils, metastasis, neoplasm staging
References
1. Scully C, Field JK, Tanzawa H. Genetic aberrations in oral or head and neck squamous cell carcinoma (SCCHN): 1. Carcinogen metabolism, DNA repair and cell cycle control. Oral Oncol. 2000; 36:256-63.
2. Moore SR, Johnson NW, Pierce AM, Wilson DF. The epidemiology of mouth cancer: a review of global incidence. Oral Dis. 2000; 6:65-74.
3. Jefferies S, Foulkes WD. Genetic mechanisms in squamous cell carcinoma of the head and neck. Oral Oncol. 2001; 37:115-26.
4. Williams HK. Molecular pathogenesis of oral squamous cell carcinoma. J Clin Mol Pathol. 2000; 53:165-72.
5. Bànkfalvi A, Piffkò J. Prognostic and predicitive factors in oral cancer: the role of the invasive tumour front. J Oral Pathol Med. 2000; 29:291-8.
6. Bryne M. New malignancy grading is a better prognostic indicator than Broders’ grading in oral squamous cell carcinomas. J Oral Pathol Med. 1989; 18:432-7.
7. Bryne M. Prognostic value of various molecular. J Oral Pathol Med. 1991; 20:413-20.
8. Bryne M. Reproducibility of two malignancy grading systems with reportedly prognostic value for oral cancer patients. J Oral Pathol Med. 1991; 20:369-72.
9. Bryne M. Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value. J Pathol. 1992; 166:375-81.
10. Bryne M. Histological grading in the deep invasive front of T1 and T2 glottic squamous cell carcinomas has high prognostic value. Virchow Arch. 1995; 427:277-81.
11. Bryne M, Boysen M, Alfsen CG. The invasive front of carcinomas. The most important part for tumour prognostication? Anticancer Res. 1998; 18:4757-64.
12. Bryne M. Is the invasive front of an oral carcinoma the most important area for prognostication? Oral Dis. 1998; 4:70-7.
13. Noguchi M, Kinjyo H, Kohama GI, Nakamori K. Invasive front in oral squamous cell carcinoma: image and flow cytometric analysis with clinicopathologic correlation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002; 93:682-7.
14. Piffkò J, Bànkfalvi À, Öfner M, Rasch, D, Joos U, Schmid KW. Standartized AgNOR analysis of the invasive tumour front in oral squamous cell carcinomas. J Pathol. 1997; 182:450-6.
15. Weller PF, Goetzl EJ. The human eosinophil. Am J Pathol. 1980; 100:794-80.
16. Pretlow TP, Keith EF, Cryar AK. Eosinophil infiltration of human colonic carcinomas as a prognostic indicator. Cancer. 1983; 43:2997-3000.
17. Lowe D, Fletcher CDM, Gower RL. Tumor-associated eosinophilia in the bladder. J Clin Pathol. 1984;37:500-02.
18. Lowe D, Fletcher CDM. Tumor-associated eosinophilia: a review. Histopathol. 1984; 8:627-32.
19. Iwasaki K, Toriju M, Fujimura T. Malignant tumor and eosinophils. Cancer. 1987; 58:1321-7.
20. Goldsmith MM, Cresson DH, Askin FB. The prognostic significance of stromal eosinophilia in head and neck cancer. Otolaryngol Head Neck Surg. 1987; 96:319-24.
21. Goldsmith MM, Belchis DA, Cresson DH, Merrit WD, Askin FB. The importance of the eosinophil in head and neck cancer. Otolaryngol Head Neck Surg. 1992; 106:106-27.
22. Tepper RI, Coffman RL, Leder P. An eosinophis-dependent mechanism for the antitumor effect of interleukin-4. Science. 1992; 257:548-51.
23. Tepper RI. The eosinophil-mediated antitumor activity of interleukin-4. J Allergy Clin Immunol. 1994; 94:1225-31.
24. Samoszuk M. Eosinophils and human cancer. Histol Histopathol. 1997; 12:807-12.
25. Wong DTW, Weller PF, Galli SJ, Elovic A, Rand TH, Gallagher GT, et al. Human eosinophils express transforming growth factor-alpha. J Exp Med. 1990; 172: 673-81.
26. Wong DTW, Bowen SM, Elovic A, Gallagher GT, Weller PF. Eosinophil ablation and tumor development. Oral Oncol. 1999; 35:496-501.
27. Dorta RG. Eosinofilia tecidual como fator de prognóstico em carcinomas espinocelulares de boca [Dissertação de Mestrado]. Bauru: Faculdade de Odontologia da USP; 2000.
28. Anneroth G, Batsakis J, Luna M. Review of the literature and a recommended system of malignancy grading in oral squamous cell carcinomas. Scand J Dent Res. 1987; 95:229-49.
29. Fisher ER, Rockette H, Jones J, Caplan R, Fisher B, et al. Prognostic significance of eosinophils and mast cell in rectal cancer: findings front the National Surgical Adjuvant Breast and Bowel Project (Protocol R-01). Human Pathol. 1989; 20:159-63.
30. Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H. The central role of CD4+ T cells in the antitumor immune response. J Exp Med. 1998; 188:2357-68.
31. Schleimer RP, Sterbinsky SA, Kaiser J, Bickel CA, Klunk DA, Tomioka K, et al. IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. Association with expression of VCAM-1. J Immunol. 1992; 148:1086-92.
32. Ghiabi M, Gallagher GT, Wong TW. Eosinophils, tissue eosinophilia, and eosinophil-derived transforming growth factor α in hamster oral carinogenesis. Cancer Res. 1992; 52:389-93.
33. Todd R, Chou MY, Matossian K, Gallagher GT, Donoff RB, Wong DTW. Cellular sources of transforming growth factor-alpha in human oral cancer. J Dent Res. 1991; 70:917-23.
34. Todd R, Wong DTW. Epidermal growth factor receptor (EGFR) biology and human oral cancer. Histol Histopathol. 1999; 14:491-500.
35. Wang JM, Deng X, Gong W, Su S. Chemokines and their role in tumor growth and metastasis. J Immunol Methods. 1988; 220:1-17.
36. Resnick MB, Weller PF. Mechanisms of eosinophil recruitment. Am J Resp Cell Mol Biol. 1993; 8:349-55.
37. Mamelle G, Pampurik J, Luboinski B, Lancar R, Lusinchi A, Bosq J. Lymph node prognostic factors in head and neck squamous cell carcinomas. Am J Surg. 1994; 168:494-8.
38. Shingaki S, Nomura T, Takada M, Kobayashi T, Nakajima T. The impact of extranodal spread of lympho node metastases in patients with oral cancer. Int J Oral Maxillofac Surg. 1999; 28:279-84.
39. Curran S, Murray G. Matrix metalloproteinases in tumour invasion and metastasis. J Pathol. 1999; 189: 300-8.
40. Johansson N, Kähari VM. Matrix metalloproteinases in squamous cell carcinoma. Histol Histopathol. 2000; 15:225-37
41. Kurahara SI, Shinohara M, Ikebe T, Nakamura S, Beppu M, Hiraki A, et al. Expression of MMPs, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity: correlations with tumor invasion and metastasis. Head Neck. 1999; 21:627-38.
42. Thomas GT, Lewis MP, Speight PM. Matrix metalloproteinases and oral cancer. Oral Oncol. 1999; 35:227-33.
43. Davoine AF, Sim T, Wierzbicki C, Leong L, Puttagunta T, McGaw DY, et al. Human eosinophils express granzyme B and perforin: potential role in tumour killing in oral squamous cancer. J Allergy Clin Immunol. 2006; 117 (Supl): S15.