Abstract
Aim—To investigate the expression of p53 protein in invasive squamous cell carcinoma (SCC) of the larynx and dysplasia in relation to histological grade and tobacco smoking.
Method—Paraffin wax embedded tissue sections from 41 cases of invasive SCC of the larynx, 28 cases of dysplasia and 14 control laryngeal biopsy specimens were studied immunohistochemically using two anti-p53 monoclonal antibodies (DO7 and 1801). The Streptavidin/horseradish peroxidase method was used after microwave antigen retrieval and a semiquantitative method was applied to assess the extent of p53 expression.
Results—Of the cases of invasive SCC of the larynx, 78% (32/41), regardless of histological grade, overexpressed p53 compared with only 30% (eight of 28) of cases of mild dysplasia. A gradual increase in p53 expression from mild to severe dysplasia (60%) was observed, and only three of 14 control biopsy specimens of laryngeal nodules showed occasional weakly positive basal cells.
Conclusion—The gradual increase in p53 expression from mild to severe dysplasia to invasive SCC indicates that p53 overexpression is an early event in laryngeal carcinogenesis which may lead to invasive malignancy. p53 overexpression may be related to environmental factors as most of the patients smoked tobacco. Microwave postfixation may be essential for the reliable detection of p53.
Keywords: p53, squamous cell carcinoma, dysplasia, larynx
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- Anwar K., Nakakuki K., Imai H., Naiki H., Inuzuka M. Over-expression of p53 protein in human laryngeal carcinoma. Int J Cancer. 1993 Apr 1;53(6):952–956. doi: 10.1002/ijc.2910530615. [DOI] [PubMed] [Google Scholar]
- Baker S. J., Preisinger A. C., Jessup J. M., Paraskeva C., Markowitz S., Willson J. K., Hamilton S., Vogelstein B. p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res. 1990 Dec 1;50(23):7717–7722. [PubMed] [Google Scholar]
- Banks L., Matlashewski G., Crawford L. Isolation of human-p53-specific monoclonal antibodies and their use in the studies of human p53 expression. Eur J Biochem. 1986 Sep 15;159(3):529–534. doi: 10.1111/j.1432-1033.1986.tb09919.x. [DOI] [PubMed] [Google Scholar]
- Bosari S., Roncalli M., Viale G., Bossi P., Coggi G. p53 immunoreactivity in inflammatory and neoplastic diseases of the uterine cervix. J Pathol. 1993 Apr;169(4):425–430. doi: 10.1002/path.1711690407. [DOI] [PubMed] [Google Scholar]
- Brachman D. G., Graves D., Vokes E., Beckett M., Haraf D., Montag A., Dunphy E., Mick R., Yandell D., Weichselbaum R. R. Occurrence of p53 gene deletions and human papilloma virus infection in human head and neck cancer. Cancer Res. 1992 Sep 1;52(17):4832–4836. [PubMed] [Google Scholar]
- Chiba I., Takahashi T., Nau M. M., D'Amico D., Curiel D. T., Mitsudomi T., Buchhagen D. L., Carbone D., Piantadosi S., Koga H. Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group. Oncogene. 1990 Oct;5(10):1603–1610. [PubMed] [Google Scholar]
- Chiu K. Y. Use of microwaves for rapid immunoperoxidase staining of paraffin sections. Med Lab Sci. 1987 Jan;44(1):3–5. [PubMed] [Google Scholar]
- Cuevas E. C., Bateman A. C., Wilkins B. S., Johnson P. A., Williams J. H., Lee A. H., Jones D. B., Wright D. H. Microwave antigen retrieval in immunocytochemistry: a study of 80 antibodies. J Clin Pathol. 1994 May;47(5):448–452. doi: 10.1136/jcp.47.5.448. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dolcetti R., Doglioni C., Maestro R., Gasparotto D., Barzan L., Pastore A., Romanelli M., Boiocchi M. p53 over-expression is an early event in the development of human squamous-cell carcinoma of the larynx: genetic and prognostic implications. Int J Cancer. 1992 Sep 9;52(2):178–182. doi: 10.1002/ijc.2910520204. [DOI] [PubMed] [Google Scholar]
- Field J. K., Spandidos D. A., Malliri A., Gosney J. R., Yiagnisis M., Stell P. M. Elevated P53 expression correlates with a history of heavy smoking in squamous cell carcinoma of the head and neck. Br J Cancer. 1991 Sep;64(3):573–577. doi: 10.1038/bjc.1991.352. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Field J. K., Spandidos D. A., Stell P. M. Overexpression of p53 gene in head-and-neck cancer, linked with heavy smoking and drinking. Lancet. 1992 Feb 22;339(8791):502–503. doi: 10.1016/0140-6736(92)91122-o. [DOI] [PubMed] [Google Scholar]
- Finlay C. A., Hinds P. W., Levine A. J. The p53 proto-oncogene can act as a suppressor of transformation. Cell. 1989 Jun 30;57(7):1083–1093. doi: 10.1016/0092-8674(89)90045-7. [DOI] [PubMed] [Google Scholar]
- Fisher C. J., Gillett C. E., Vojtesek B., Barnes D. M., Millis R. R. Problems with p53 immunohistochemical staining: the effect of fixation and variation in the methods of evaluation. Br J Cancer. 1994 Jan;69(1):26–31. doi: 10.1038/bjc.1994.4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harris A. L. Cancer genes. Telling changes of base. Nature. 1991 Apr 4;350(6317):377–378. doi: 10.1038/350377a0. [DOI] [PubMed] [Google Scholar]
- Hinds M. W., Thomas D. B., O'Reilly H. P. Asbestos, dental X-rays, tobacco, and alcohol in the epidemiology of laryngeal cancer. Cancer. 1979 Sep;44(3):1114–1120. doi: 10.1002/1097-0142(197909)44:3<1114::aid-cncr2820440346>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
- Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
- Iggo R., Gatter K., Bartek J., Lane D., Harris A. L. Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet. 1990 Mar 24;335(8691):675–679. doi: 10.1016/0140-6736(90)90801-b. [DOI] [PubMed] [Google Scholar]
- Isobe M., Emanuel B. S., Givol D., Oren M., Croce C. M. Localization of gene for human p53 tumour antigen to band 17p13. Nature. 1986 Mar 6;320(6057):84–85. doi: 10.1038/320084a0. [DOI] [PubMed] [Google Scholar]
- Lambkin H. A., Mothersill C. M., Kelehan P. Variations in immunohistochemical detection of p53 protein overexpression in cervical carcinomas with different antibodies and methods of detection. J Pathol. 1994 Jan;172(1):13–18. doi: 10.1002/path.1711720105. [DOI] [PubMed] [Google Scholar]
- Levine A. J., Perry M. E., Chang A., Silver A., Dittmer D., Wu M., Welsh D. The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis. Br J Cancer. 1994 Mar;69(3):409–416. doi: 10.1038/bjc.1994.76. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maestro R., Dolcetti R., Gasparotto D., Doglioni C., Pelucchi S., Barzan L., Grandi E., Boiocchi M. High frequency of p53 gene alterations associated with protein overexpression in human squamous cell carcinoma of the larynx. Oncogene. 1992 Jun;7(6):1159–1166. [PubMed] [Google Scholar]
- McLaren R., Kuzu I., Dunnill M., Harris A., Lane D., Gatter K. C. The relationship of p53 immunostaining to survival in carcinoma of the lung. Br J Cancer. 1992 Oct;66(4):735–738. doi: 10.1038/bjc.1992.348. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ogden G. R., Lane D. P., Chisholm D. M. p53 expression in dyskeratosis congenita: a marker for oral premalignancy? J Clin Pathol. 1993 Feb;46(2):169–170. doi: 10.1136/jcp.46.2.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Poller D. N., Hutchings C. E., Galea M., Bell J. A., Nicholson R. A., Elston C. W., Blamey R. W., Ellis I. O. p53 protein expression in human breast carcinoma: relationship to expression of epidermal growth factor receptor, c-erbB-2 protein overexpression, and oestrogen receptor. Br J Cancer. 1992 Sep;66(3):583–588. doi: 10.1038/bjc.1992.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Recio L., Sisk S., Pluta L., Bermudez E., Gross E. A., Chen Z., Morgan K., Walker C. p53 mutations in formaldehyde-induced nasal squamous cell carcinomas in rats. Cancer Res. 1992 Nov 1;52(21):6113–6116. [PubMed] [Google Scholar]
- Scheffner M., Huibregtse J. M., Vierstra R. D., Howley P. M. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell. 1993 Nov 5;75(3):495–505. doi: 10.1016/0092-8674(93)90384-3. [DOI] [PubMed] [Google Scholar]
- Somers K. D., Merrick M. A., Lopez M. E., Incognito L. S., Schechter G. L., Casey G. Frequent p53 mutations in head and neck cancer. Cancer Res. 1992 Nov 1;52(21):5997–6000. [PubMed] [Google Scholar]
- Vojtesek B., Bártek J., Midgley C. A., Lane D. P. An immunochemical analysis of the human nuclear phosphoprotein p53. New monoclonal antibodies and epitope mapping using recombinant p53. J Immunol Methods. 1992 Jul 6;151(1-2):237–244. doi: 10.1016/0022-1759(92)90122-a. [DOI] [PubMed] [Google Scholar]
- Wynford-Thomas D. P53 in tumour pathology: can we trust immunocytochemistry? J Pathol. 1992 Apr;166(4):329–330. doi: 10.1002/path.1711660402. [DOI] [PubMed] [Google Scholar]


