P53 overexpression in epidermoid carcinoma of the head and neck
Keywords:
P53, squamous cell carcinoma, head and neck cancer, immunohistochemistryAbstract
The theory of field cancerization in tumors of the head and neck reflects the complex oncogenesis that occurs in this region. The mechanisms that control cell proliferation at the molecular level in epidermoid carcinomas (ECs) of the upper aerodigestive tract are still unclear. Mutations in p53 are the genetic alterations most often detected in ECs of the head and neck and seem to contribute actively to the carcinogenic process triggered by p53 as a tumor-suppressor gene and to its association with tobacco. The objective of the present study was to investigate the expression of p53 protein in epidermoid head and neck carcinomas by immunohistochemistry and its immunohistochemical correlation with other prognostic factors. The study was conducted on 63 consecutive ECs cases not submitted to previous treatment. Specimens of the tumor and of the normal adjacent mucosa were collected during surgery and submitted to immunohistochemical reaction for the determination of the expression of anti-protein p53 antibody (M7001 DAKO A/S, Denmark). Anatomo-clinical and demographic data were not significantly correlated with the presence of lymph node metastases or p53 expression in the tumor or in the adjacent normal mucosa. Tumor localization in the larynx was significantly correlated with p53 expression. Histological grading as grades I, II, Ill and IV was correlated with significant p53 expression (p = 0.025). Conclusions: 1) in the studied material obtained from 63 cases of head and neck ECs, we detected a 48 percent rate of immunohistochemically detectable p53 overexpression; 2) we did not detect a relationship between demographic patient data and p53 expression in the tumor or in the normal adjacent mucosa; 3) p53 overexpression was significantly more frequent in ECs material from the larynx; and 4) The presence of 12 cases with p53 overexpression in the normal adjacent mucosa and with a p53-negative tumor is in agreement with the theory of field cancerization. Follow-up of this patient series for a longer period of time will permit a better analysis of these values.
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References
Burns JE, Baird MC, Clark LJ, et al. Gene mutations and increased levels of p53 protein in human squamous-cell carcinomas and their cell lines. Br J Cancer 1993;67:1274-84.
Brachman DG, Beckett M, Graves D, et al. p53 mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines. Cancer Res 1993;53:3667-9.
Brachman DG, Graves D, Vokes E, et al. Occurrence of p53 gene deletions and human papilloma virus infection in human head and neck cancer. Cancer Res 1992;52:4832-6.
Brennan JA, Boyle JO, Koch WM, et al. Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck. N Engl J Med 1995;332(11):712-17.
Chang F, Syrjanen A, Tervahauta A, et al. Tumorigenesis associated with the p53 tumor-suppressor gene. Br J Cancer 1993;68:653-61.
Chen PL ,Chen Y, Bookstein R, Lee WH. Genetic mechanisms of tumor suppression by the human p53 gene. Science 1990;250:576-9.
Chung KY, Mukhopadhyay T, Kim J, et al. Discordant p53 mutations in primary head and neck cancers and corresponding second primary cancers of upper aerodigestive tract. Cancer Res 1993;53:1676-83.
Donehower LA, Bradley A. The tumor suppressor p53. Biochemica et Biophysica Acta 1993;155:181-205.
Field JK. Oncogenes and tumor-suppressor genes in squamous cell carcinoma of the head and neck. Oral oncol Eur J Cancer 1992;28B(1)67-76.
Field JK, Spandidos DA, Malliri A. Elevated p53 expression correlates with a history of heavy smoking in squamous-cell carcinoma of the head and neck. Br J Cancer 1991;64:573-77.
Finlay CA, Hinds PW, Levine AJ. The p53 proto-oncogene can act as a suppressor of transformation. Cell 1989;57:1083-93.
Franco LE, Kowalski LP, Kanda JL. Risk factors for second cancers of the upper respiratory and digestive systems: A case-control study. J Clin Epidemic 1991;4(7):615-25.
Frank, JL Bur ME, Garb JL, et al. p53 tumor suppressor oncogene expression in squamous-cell carcinoma of the hypopharinx. Cancer 1994;73(1):181-6.
Guterson BA, Anbazhagan R, Warren W, et al. Expression of p53 premalignant ad malignant squamous epithelium. Oncogene 1991;6:85-9.
Harris CC, Hollstein M. Clinical implications of the p53 tumor suppressor gene. N Engl J Med 1993; Oct 28:1318-25.
Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991;253:49-53.
Knudson A, Genetics of tumors of the head and neck. Arch Otolaryngol Head Neck Surg 1993;119:735-7.
Lamb P, Crawford ML. Characterization of the human p53 gene. Mol Cel Biol 1986;6:1379-85.
Lake D. Worrying about p53. Current Biol 1992;2(11):581-3.
Lee NK, Ye YW, Chen J. p53, retinoblastoma, and human papilloma virus in squamous-cell carcinoma and adjacent normal mucos of the upper aerodigestive tract. Arch Otolaringol Head Neck Surg 1993;119:1125-31. 1992;
Leonard HL, Kearsley JH, Chenovix-Trench G, et al. Analysis of gene amplification in head and neck squamous-cell carcinomas. Int J Cancer 1991:48:511-15.
Levine AJ. The road to the discovery of the p53 protein. Int J Cancer 1994;56:775-6.
Levine AJ, Momand J, Finlay CA, The p53 tumor suppressor gene. Nature 1991;351:453-6.
Maestro R, Dolcetti R, Gasparotto D, et al. High frequency of p53 gene alterations associated with protein overexpression in human squamous-cell carcinoma o the larynx. Oncogene 1992, 7:1159-66.
Malkin D, Jolly KW, Barbier N, et al. Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. N Engl J Med 1992;326:1309-25.
McBride OW, Merry D, Vivol D. The gene for the p53 cellular tumor antigen is localized on chromosome 17 short arm (17p13). Proc Nall Acad Sci USA 1986;83:130-4.
Nadal A, Campo E, Pinto J, et al. p53 expression in normal, dysplastic, and neoplastic laryngeal epithelium. Absence of a correlation with prognostic factors. J Path 1.995;175:181-8.
Nagai MA, Miracca EC, Yamamoto L, Kowalski LP, Brentani RR. TP53 mutations in upper aerodigestive squamous-cell carcinomas from a group of Brazilian patients. A J Surg 1996;170:92-4.
Nees M, Homann N, Discher H, et al. Expression of mutated p53 in tumor-distant epithelia of head and neck cancer patients: A possible molecular basis for the development of multiple tumors. Cancer Res 1993;53:4189-96.
Nigro JM, Baker SJ, Preisinger AC, et al. Mutations in the p53 gene occur in diverse human tumor types. Nature 1989;342:705-9.
Reiss M, Vellucci VF, Zhou ZL. Mutant p53 suppressor gene causes resistance to transforming growth factor in murine keratinocytes. Cancer Res 1993;53:899-04.
Shin DM, Kim J, Ro JY, et al. Activation of p53 gene expression in premalignant lesions during head and neck tumorigenesis. Cancer Res 1994;54:321-6.
Slaughter DP, Southwick HW, Smejkal, W. "Field Cancerization" in oral stratified squamous epithelium. Cancer 1953;6:963-8.
Somers KD, Merrick A, Lopez ME, et al. Frequent p53 mutations in head and neck cancer. Cancer Res 1992;52:5997-6000.
Weinberg RA. Oncogenes, antioncogenes and molecular basis of multistep carcinogenesis. Cancer Res 1989;49:3713-8.
Weinberg WC, Azzoli CG, Chapman K, et al. p53-mediated transcriptional activity increases in differentiating epidermal keratinocytes in association with decreased p53 protein. Oncogene 1995;10:2271-9.
Yin XY, Smith ML, Witesade TL, et al. Abnormalities in the p53 gene in tumors and cell lines of human squamous-cell carcinomas of the head and neck. Int J Cancer 1993;54:322-7.