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. 1995 Oct;48(5):M269–M272. doi: 10.1136/mp.48.5.m269

Altered p53 in microdissected, metachronous, premalignant and malignant oral lesions from the same patients

Y-Q Li 1,2,3,4, Z P Pavelic 1,2,3,4, L-J Wang 1,2,3,4, J S McDonald 1,2,3,4, L Gleich 1,2,3,4, E Munck-Wikland 1,2,3,4, S Dacic 1,2,3,4, Z Danilovic 1,2,3,4, L J Pavelic 1,2,3,4, K M Wilson 1,2,3,4, J L Gluckman 1,2,3,4, P J Stambrook 1,2,3,4
PMCID: PMC407983  PMID: 16696020

Abstract

Aims—To determine whether mutant p53 alleles harboured by malignant tumours of the oral cavity were also present in previous premalignant lesions at the same site.

Methods—Paraffin embedded tumour specimens along with their premalignant counterparts were analysed for p53 alterations using immunohistochemistry, microdissection, polymerase chain reaction amplification, and DNA sequencing.

Results—Malignant lesions from five of eight patients showed overexpression of p53 protein by immunohistochemistry. Upon DNA sequencing, two of these five specimens had p53 mutations. Of the five patients whose cancers showed p53 overexpression by immunohistochemistry, three had previous premalignant lesions that also had immunohistochemically detectable p53 protein. However, DNA sequencing showed that none of these three had mutations in the p53 gene. The remaining five premalignant lesions had no immunohistochemically detectable p53 protein.

Conclusions—Some premalignant lesions have increased p53 protein which can be detected by staining with antibody to p53. This staining is not caused by mutations in p53 that are found in subsequent tumours at the same site.

Keywords: Oral cancer

Keywords: p53 gene

Keywords: mutations

Keywords: loss of heterozygosity

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Selected References

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  1. Baker S. J., Fearon E. R., Nigro J. M., Hamilton S. R., Preisinger A. C., Jessup J. M., vanTuinen P., Ledbetter D. H., Barker D. F., Nakamura Y. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science. 1989 Apr 14;244(4901):217–221. doi: 10.1126/science.2649981. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Bennett W. P., Colby T. V., Travis W. D., Borkowski A., Jones R. T., Lane D. P., Metcalf R. A., Samet J. M., Takeshima Y., Gu J. R. p53 protein accumulates frequently in early bronchial neoplasia. Cancer Res. 1993 Oct 15;53(20):4817–4822. [PubMed] [Google Scholar]
  4. Berenson J. R., Yang J., Mickel R. A. Frequent amplification of the bcl-1 locus in head and neck squamous cell carcinomas. Oncogene. 1989 Sep;4(9):1111–1116. [PubMed] [Google Scholar]
  5. Biegel J. A., Burk C. D., Barr F. G., Emanuel B. S. Evidence for a 17p tumor related locus distinct from p53 in pediatric primitive neuroectodermal tumors. Cancer Res. 1992 Jun 15;52(12):3391–3395. [PubMed] [Google Scholar]
  6. Buchman V. L., Chumakov P. M., Ninkina N. N., Samarina O. P., Georgiev G. P. A variation in the structure of the protein-coding region of the human p53 gene. Gene. 1988 Oct 30;70(2):245–252. doi: 10.1016/0378-1119(88)90196-5. [DOI] [PubMed] [Google Scholar]
  7. Campo E., de la Calle-Martin O., Miquel R., Palacin A., Romero M., Fabregat V., Vives J., Cardesa A., Yague J. Loss of heterozygosity of p53 gene and p53 protein expression in human colorectal carcinomas. Cancer Res. 1991 Aug 15;51(16):4436–4442. [PubMed] [Google Scholar]
  8. Cornelis R. S., van Vliet M., Vos C. B., Cleton-Jansen A. M., van de Vijver M. J., Peterse J. L., Khan P. M., Børresen A. L., Cornelisse C. J., Devilee P. Evidence for a gene on 17p13.3, distal to TP53, as a target for allele loss in breast tumors without p53 mutations. Cancer Res. 1994 Aug 1;54(15):4200–4206. [PubMed] [Google Scholar]
  9. Cunningham J., Lust J. A., Schaid D. J., Bren G. D., Carpenter H. A., Rizza E., Kovach J. S., Thibodeau S. N. Expression of p53 and 17p allelic loss in colorectal carcinoma. Cancer Res. 1992 Apr 1;52(7):1974–1980. [PubMed] [Google Scholar]
  10. 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]
  11. Gao H., Wang L. D., Zhou Q., Hong J. Y., Huang T. Y., Yang C. S. p53 tumor suppressor gene mutation in early esophageal precancerous lesions and carcinoma among high-risk populations in Henan, China. Cancer Res. 1994 Aug 15;54(16):4342–4346. [PubMed] [Google Scholar]
  12. 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]
  13. Jones M. H., Nakamura Y. Detection of loss of heterozygosity at the human TP53 locus using a dinucleotide repeat polymorphism. Genes Chromosomes Cancer. 1992 Jul;5(1):89–90. doi: 10.1002/gcc.2870050113. [DOI] [PubMed] [Google Scholar]
  14. Largey J. S., Meltzer S. J., Yin J., Norris K., Sauk J. J., Archibald D. W. Loss of heterozygosity of p53 in oral cancers demonstrated by the polymerase chain reaction. Cancer. 1993 Mar 15;71(6):1933–1937. doi: 10.1002/1097-0142(19930315)71:6<1933::aid-cncr2820710602>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  15. Levine A. J., Momand J., Finlay C. A. The p53 tumour suppressor gene. Nature. 1991 Jun 6;351(6326):453–456. doi: 10.1038/351453a0. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Mashberg A. Erythroplasia vs. leukoplasia in the diagnosis of early asymptomatic oral squamous carcinoma. N Engl J Med. 1977 Jul 14;297(2):109–110. doi: 10.1056/NEJM197707142970212. [DOI] [PubMed] [Google Scholar]
  18. Miller C. W., Simon K., Aslo A., Kok K., Yokota J., Buys C. H., Terada M., Koeffler H. P. p53 mutations in human lung tumors. Cancer Res. 1992 Apr 1;52(7):1695–1698. [PubMed] [Google Scholar]
  19. Nelson W. G., Kastan M. B. DNA strand breaks: the DNA template alterations that trigger p53-dependent DNA damage response pathways. Mol Cell Biol. 1994 Mar;14(3):1815–1823. doi: 10.1128/mcb.14.3.1815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nigro J. M., Baker S. J., Preisinger A. C., Jessup J. M., Hostetter R., Cleary K., Bigner S. H., Davidson N., Baylin S., Devilee P. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989 Dec 7;342(6250):705–708. doi: 10.1038/342705a0. [DOI] [PubMed] [Google Scholar]
  21. Nishida N., Fukuda Y., Kokuryu H., Toguchida J., Yandell D. W., Ikenega M., Imura H., Ishizaki K. Role and mutational heterogeneity of the p53 gene in hepatocellular carcinoma. Cancer Res. 1993 Jan 15;53(2):368–372. [PubMed] [Google Scholar]
  22. Ogden G. R., Kiddie R. A., Lunny D. P., Lane D. P. Assessment of p53 protein expression in normal, benign, and malignant oral mucosa. J Pathol. 1992 Apr;166(4):389–394. doi: 10.1002/path.1711660411. [DOI] [PubMed] [Google Scholar]
  23. Pavelic K., Pavelic Z. P., Denton D., Reising J., Khalily M., Preisler H. D. Immunohistochemical detection of c-myc oncoprotein in paraffin embedded tissues. J Exp Pathol. 1990;5(4):143–153. [PubMed] [Google Scholar]
  24. Pavelic Z. P., Li Y. Q., Stambrook P. J., McDonald J. S., Munck-Wikland E., Pavelic K., Dacic S., Danilovic Z., Pavelic L., Mugge R. E. Overexpression of p53 protein is common in premalignant head and neck lesions. Anticancer Res. 1994 Sep-Oct;14(5B):2259–2266. [PubMed] [Google Scholar]
  25. Pavelic Z. P., Portugal L. G., Gootee M. J., Stambrook P. J., Smith C., Mugge R. E., Pavelic L., Wilson K., Buncher C. R., Li Y. Q. Retrieval of p53 protein in paraffin-embedded head and neck tumor tissues. Arch Otolaryngol Head Neck Surg. 1993 Nov;119(11):1206–1209. doi: 10.1001/archotol.1993.01880230048008. [DOI] [PubMed] [Google Scholar]
  26. Reifenberger G., Liu L., Ichimura K., Schmidt E. E., Collins V. P. Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations. Cancer Res. 1993 Jun 15;53(12):2736–2739. [PubMed] [Google Scholar]
  27. Sameshima Y., Matsuno Y., Hirohashi S., Shimosato Y., Mizoguchi H., Sugimura T., Terada M., Yokota J. Alterations of the p53 gene are common and critical events for the maintenance of malignant phenotypes in small-cell lung carcinoma. Oncogene. 1992 Mar;7(3):451–457. [PubMed] [Google Scholar]
  28. Sato T., Tanigami A., Yamakawa K., Akiyama F., Kasumi F., Sakamoto G., Nakamura Y. Allelotype of breast cancer: cumulative allele losses promote tumor progression in primary breast cancer. Cancer Res. 1990 Nov 15;50(22):7184–7189. [PubMed] [Google Scholar]
  29. Saxena A., Clark W. C., Robertson J. T., Ikejiri B., Oldfield E. H., Ali I. U. Evidence for the involvement of a potential second tumor suppressor gene on chromosome 17 distinct from p53 in malignant astrocytomas. Cancer Res. 1992 Dec 1;52(23):6716–6721. [PubMed] [Google Scholar]
  30. Shi S. R., Key M. E., Kalra K. L. Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem. 1991 Jun;39(6):741–748. doi: 10.1177/39.6.1709656. [DOI] [PubMed] [Google Scholar]
  31. Shin D. M., Kim J., Ro J. Y., Hittelman J., Roth J. A., Hong W. K., Hittelman W. N. Activation of p53 gene expression in premalignant lesions during head and neck tumorigenesis. Cancer Res. 1994 Jan 15;54(2):321–326. [PubMed] [Google Scholar]
  32. Shklar G. S. Oral leukoplakia. N Engl J Med. 1986 Dec 11;315(24):1544–1546. doi: 10.1056/NEJM198612113152408. [DOI] [PubMed] [Google Scholar]
  33. Somers K. D., Cartwright S. L., Schechter G. L. Amplification of the int-2 gene in human head and neck squamous cell carcinomas. Oncogene. 1990 Jun;5(6):915–920. [PubMed] [Google Scholar]
  34. 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]
  35. Sommer S. S., Cunningham J., McGovern R. M., Saitoh S., Schroeder J. J., Wold L. E., Kovach J. S. Pattern of p53 gene mutations in breast cancers of women of the midwestern United States. J Natl Cancer Inst. 1992 Feb 19;84(4):246–252. doi: 10.1093/jnci/84.4.246. [DOI] [PubMed] [Google Scholar]
  36. Sozzi G., Miozzo M., Donghi R., Pilotti S., Cariani C. T., Pastorino U., Della Porta G., Pierotti M. A. Deletions of 17p and p53 mutations in preneoplastic lesions of the lung. Cancer Res. 1992 Nov 1;52(21):6079–6082. [PubMed] [Google Scholar]
  37. Spandidos D. A., Lamothe A., Field J. K. Multiple transcriptional activation of cellular oncogenes in human head and neck solid tumours. Anticancer Res. 1985 Mar-Apr;5(2):221–224. [PubMed] [Google Scholar]
  38. Voravud N., Shin D. M., Ro J. Y., Lee J. S., Hong W. K., Hittelman W. N. Increased polysomies of chromosomes 7 and 17 during head and neck multistage tumorigenesis. Cancer Res. 1993 Jun 15;53(12):2874–2883. [PubMed] [Google Scholar]
  39. Wagata T., Shibagaki I., Imamura M., Shimada Y., Toguchida J., Yandell D. W., Ikenaga M., Tobe T., Ishizaki K. Loss of 17p, mutation of the p53 gene, and overexpression of p53 protein in esophageal squamous cell carcinomas. Cancer Res. 1993 Feb 15;53(4):846–850. [PubMed] [Google Scholar]
  40. Watling D. L., Gown A. M., Coltrera M. D. Overexpression of p53 in head and neck cancer. Head Neck. 1992 Nov-Dec;14(6):437–444. doi: 10.1002/hed.2880140603. [DOI] [PubMed] [Google Scholar]
  41. Yamaguchi T., Toguchida J., Yamamuro T., Kotoura Y., Takada N., Kawaguchi N., Kaneko Y., Nakamura Y., Sasaki M. S., Ishizaki K. Allelotype analysis in osteosarcomas: frequent allele loss on 3q, 13q, 17p, and 18q. Cancer Res. 1992 May 1;52(9):2419–2423. [PubMed] [Google Scholar]
  42. Yokota J., Tsunetsugu-Yokota Y., Battifora H., Le Fevre C., Cline M. J. Alterations of myc, myb, and rasHa proto-oncogenes in cancers are frequent and show clinical correlation. Science. 1986 Jan 17;231(4735):261–265. doi: 10.1126/science.3941898. [DOI] [PubMed] [Google Scholar]

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