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Arquivos Internacionais de Otorrinolaringologia 2011; 15(01): 041-047
DOI: 10.1590/S1809-48722011000100006
Original Article
Thieme Publicações Ltda Rio de Janeiro, Brazil

Expression of p53 in the Tumor and Oral Epithelium in Patients with Cancer of Mouth and Pharynx

Expressão da p53 no Tumor e no Epitélio Oral em Pacientes com Câncer de Boca e Faringe
Fabiane Dittrich Santos
*   Master's Degree in surgery from the Medical College of Botucatu. Dental Surgeon.
,
Jair Montovani
**   Lecturer in Otorhinolaryngology. Coordinator of Discipline in PG sensus stricto.
,
Cleverson Teixeira Soares
***   Doctoral Degree. Doctor in Pathology of the Base Hospital of Bauru - SP.
,
Lídia Raquel de Carvalho
****   Doctoral Degree. Doctor Professor of the Biosciences Institute of Botucatu - Unesp.
› Author Affiliations
Further Information

Publication History

01 September 2010

01 October 2010

Publication Date:
12 February 2014 (online)

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Summary

Introduction: Expressive percent of patients with oral and oral pharynx carcinomas presents with overexpression of protein p53 induced by tobacco, alcohol and radiotherapy.

Objective: To describe the p53 expression in areas of the normal mucosa adjacent to the tumor and in mouth and pharynx carcinomas.

Method: Prospective study with clinical follow-up of one year of 24 patients with oral and oral pharynx spinocellular carcinoma. We performed biopsies in the neoplasm and areas of the normal mucosa adjacent to the tumor, before and 9 months following radiotherapy and an immunohistochemical study of p53 expression.

Results: Before radiotherapy, there was a change to the p53 expression in 20 out of the 24 biopsies made in the neoplasm and in 14 in those of normal mucosa adjacent to the tumor. Eleven patients died 1 year before clinical follow-up. From the 2 initial patients with increase of p53 after radiotherapy it remained increased in 7 in the neoplasm region and in 6 in the normal mucosa regions. We noticed association of p53 with smoking and tumor stage (p < 5%), but not with the degree of cellular differentiation and alcoholism.

Conclusion: The increase to the p53 expression was viewed both in the neoplasm region and in the normal mucosa in most patients with oral and oral pharynx carcinoma before and after radiotherapy. There was a statistically significant correlation of the p53 expression with smoking and neoplasm stage.

Resumo

Introdução: Expressiva porcentagem de pacientes com carcinomas de boca e faringe apresentam superexpressão da proteína p53 induzida por tabaco, álcool e radioterapia.

Objetivo: Descrever a expressão da p53 em áreas de mucosa normal adjacente ao tumor e em carcinomas da boca e faringe.

Método: Estudo prospectivo, com seguimento clínico por um ano, de 24 pacientes com câncer espinocelular de boca e faringe. Foram feitas biópsias na neoplasia e em áreas de mucosa normal adjacente ao tumor, antes e 9 meses após a radioterapia, e realizado estudo imunohistoquímico da expressão da p53.

Resultados: Antes da radioterapia, houve alteração da expressão da p53 em 20 das 24 biópsias feitas na neoplasia e em 14 nas de mucosa normal adjacente ao tumor. Onze paciente morreram antes de 1 ano de seguimento clínico. Dos 2 pacientes iniciais com aumento da p53 após a radioterapia continuava aumentada em 7 na área da neoplasia e em 6 nas áreas de mucosa normal. Observou-se associação da p53 com o tabagismo e estádio do tumor (p < 5%) mas não com o grau de diferenciação celular e alcoolismo.

Conclusão: O aumento da expressão da p53 foi observado tanto na área da neoplasia como em mucosa normal na maioria dos pacientes com carcinoma de boca e faringe antes e após a radioterapia. Houve correlação estatisticamente significante da expressão da p53 com o tabagismo e estádio da neoplasia.

Keywords

mouth neoplasms - pharynx neoplasms - p53 genes - cocarcinogenesis

Palavras-chave

neoplasias bucais - neoplasias faríngeas - genes p53 - cocarcinogênese
 

  • Bibliographical References

  • 1 Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of eighteen majors cancers in 1985. Int J Cancer 1993; 54: 594-606
    CrossrefGoogle Scholar
  • 2 Kowalski LP, Franco EL, Torloni H, Fava AS, Andrade Sobrino J, Ramos G, Oliveira BV, Curodo MP. Lateness of diagnosis of oral and oropharyngeal carcinoma: factors related to the tumor, the patients and health factors. Oral Oncol Eur J Cancer 1994; 30: 167-73
    CrossrefGoogle Scholar
  • 3 Kock WM, Lanzo M, Seurel D, Zohura KM , Sidransky. Head and neck cancer in nonsmokers: a distinct clinical and molecular entity. Laryngoscope 1999; 109: 544-51
    Google Scholar
  • 4 Martin-Granizo R, Rodrigues-Campo F, Naval Z, Gonçalez FJW. Squamous cell carcinoma of the oral cavity in young people- a comprehensive literatura review. Oral Oncol 2001; 33: 401-18
    Google Scholar
  • 5 Mackenzie J, Ah-See K, Thakker M, Sloan P, Marau AG, Birch J , et al. Increasing incidence of oral cancer among young person: what is the aethiology?. Oral Oncol 2000; 36: 387-9
    CrossrefGoogle Scholar
  • 6 Schantz SP, Yu G. Head and neck cancer incidence trends in young americans, 1973-1997, with a special analysis for tongue cancer. Arch Otolaringol Head Neck Surg 2002; 128: 268-74
    Google Scholar
  • 7 Lewellyn CD, Johnson NW, Warnakulasurixa KA. Risk factors for squamous cell carcinoma of the oral cavity in young people-comprehensive: literature review. Oral Oncol 2001; 37 (5) 401-18
    CrossrefPubMedGoogle Scholar
  • 8 Rodrigo JP, Suaréz C, González MV, Lazo PS, Ramos S, Coto E, Alvarez I, García LA, Martínez JA. Variation of genetic alterations in different sites of head and neck cancer. Laryngoscope 2001; 111: 1297-01
    CrossrefGoogle Scholar
  • 9 Jones AS, Phillips DE, Husband D. Second primary tumors in patients with head and neck squamous cell carcinoma. Cancer 1995; 75: 1343-53
    CrossrefGoogle Scholar
  • 10 Cianfriglia FD, Gregorio DA, Manieri A. Mutiple primary tumor in patient with oral squamous cell carcinoma. Oral Oncol 1999; 35: 157-63
    CrossrefPubMedGoogle Scholar
  • 11 Franco EL, Kowalski LP, Kanda LL. Risk factors for second cancers of the upper respiratory and digestive systems: a case- control study. J Clin Epidemiol 1991; 44: 615-25
    Google Scholar
  • 12 Califano J, Van der Riet O, Westra W, Nawwroz H, Clyman G, Prantadon S , et al. Genetic progression model for head and neck: implications for field cancerization. Cancer Res 1996; 56: 2488-92
    Google Scholar
  • 13 Neville BW, Day TA. Oral cancer and precancerous lesions. Cancer J Clin 2002; 52: 195-215
    CrossrefGoogle Scholar
  • 14 Nagai MA, Miracca EC, Yamoto L, Kowalski LP, Bremtani RR. TP53 Mutations in upper aerodigestive squamous cell carcinomas from a group of Braziliam patients. Am J Surg 1995; 170: 492-4
    CrossrefGoogle Scholar
  • 15 Coltrera MD, Zarbo RJ, Sakr WA, Gown AM. Markers for displasya of the upper aero digestive tract. Suprabasal expression of PCNA, p53 e CK 19 in alcohol-Fixed, embebeded tissue. Am J Pathol 1992; 141: 818-25
    Google Scholar
  • 16 Veiculoscu NE, El-Deiry WS. Biological and clinical importance of the p53 tumor suppressor gene. Clin Chem 1996; 42: 858-68
    Google Scholar
  • 17 Shin DM, Kim J, Ro JY, Hittelman J, Roth JA, Hong WK, Hittelman WN. Activation of p53 gene expression in premalignant lesions during head and neck tumorigenesis. Cancer Res 1994; 54: 321-6
    Google Scholar
  • 18 Wood MW, Medina JE, Thompson GC, Houck JR, Min KW. Accumulation of the p53, supressor gene product in oral leukoplakia. Otolaryngol Head Neck Surg 1994; 111: 758-763
    CrossrefGoogle Scholar
  • 19 Regesi JA, Zarbo RJ, Regevi E, Pysanty S, Silver-Man S, Gazit D. p53, protein expression sequential biopsies of oral displasias and in situ carcinomas. J Oral Pathol Med 1995; 24: 18-22
    CrossrefGoogle Scholar
  • 20 Aguiar MCF, Araújo VC. p53 protein expression in lining epithelium adjacent to oral squamous cell carcinoma. Rev Pos Grad 1997; 4: 14-9
    Google Scholar
  • 21 Chung KY, Mukhopadhyay T, Kim J, Casson A, Ro JY, Goepfert H, Hong WK, Roth JA. Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers of the upper aerodigestive tract. Cancer Res 1993; 53: 1676-83
    Google Scholar
  • 22 Naggar AKE, Lai S, Glayman GL, Mims B, Lippman SM, Coombes M, Luna MA, Lozano G. p 73, gene alterations and expression in primary oral and laryngeal squamous carcinomas. Carcinogenesis 2001; 22: 729-35
    CrossrefGoogle Scholar
  • 23 Yoo GH, Washington J, Oliver J, Piechocki M, Kim H, Nora JF, Shibuya TY, Wilson DR, Ensley JF. The effects of exogenous p53 overexpression on hpv-immortalized and carcinogen transformed oral keratinocytes. Am Cancer Soc 2002; 94: 159-66
    Google Scholar
  • 24 Rouband-Diogene H, Fortin A, Morency R, Roy J, Monteil RA, Têtre B. Markers of radioresistance in squamous cell carcinoma of the head and neck: a clinicopathologic and imunohistochemical study. J Clin Oncol 1997; 8: 1030-8
    Google Scholar
  • 25 Couture C, Diogéne HR, Têtu B, Bairati I, Mury D, Allard J, Fortin A. p53 and ki-67 as markers of radioresistance in head and neck carcinoma. Am Cancer Soc 2002; 94: 713-22
    Google Scholar
  • 26 Gluckman JL, Pavelic ZP, Welkoborsky HJ, Mann W, Stambrook P, Gleich L, Wilson K, Righi P, Portugal LG, Mcdonald J, , Biddinger, Steward D, Gartside P. Prognostic Indicators for Squamous Cell Carcinoma of the Oral Cavity: A Clinicopathologic Correlation. Laryngoscope 1997; 107: 1239-1244
    CrossrefGoogle Scholar
  • 27 Brachman DG, Beckett M, Graves D, Haraf D, Vokes E, Weichselbaum RR. p53 mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines. Cancer Res 1993; 53: 3667-9
    Google Scholar
  • 28 Pirollo KF, Hao Z, Rait Yang YJ, Fee Wee JR, Ryan P , et al. p53 mediated sensitization of squamous carcinoma of the head and neck to radiotherapy. Oncogene 1997; 14: 1735-46
    CrossrefGoogle Scholar
  • 29 Lavertu P, Adelstein DJ, Myles J, Secic M. p53 and ki-67 as outcome predictors for advanced squamous cell cancers of head and neck treated with chemoradiotherapy. Laryngoscope 2001; 11: 1878-92
    Google Scholar
  • 30 Myers JN, Elkins T, Roberts D, Byers RM. Squamous cell carcinoma of the tongue in young adults: increasing incidence and factors that predict treatment outcomes. Otorhinolaryngol Head Neck Surg 2000; 122: 44-51
    CrossrefGoogle Scholar
  • 31 Weichselbaum RR, Kufe DW, Advani SJ, Roizman B. Molecular targeting of gene therapy and radiotherapy. Acta Oncol 2001; 40: 735-8
    CrossrefGoogle Scholar
  • 32 Goepfert H. Squamous cell carcinoma of the head and neck: past progress and future promise. CA Cancer J Clin 1998; 48: 195-198
    CrossrefGoogle Scholar
  • 33 Hamilton PW, Allen DC. Morfometry in histopathology. Journal of Pathology.
    Google Scholar