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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1994 Nov;85(11):1087–1093. doi: 10.1111/j.1349-7006.1994.tb02911.x

High Frequency of p53 Abnormality in Laryngeal Cancers of Heavy Smokers and Its Relation to Human Papillomavirus infection

Takeshi Suzuki 1,3, Kouichi Shidara 2, Futoshi Kara 1, Takashi Nakajima 1,
PMCID: PMC5919361  PMID: 7829392

Abstract

A series of 41 laryngeal squamous cell carcinomas was examined for p53 abnormalities and human papillomavirus (HPV) infection by an immunohistochemical and/or molecular approach. Immuno‐histochemically, p53 over‐expression was observed in about 60% of the cancers, of which 12 were revealed to contain point mutations of p53 by a combination of the single‐strand conformatioiial polymorphism technique and direct sequencing. The p53 point mutations ranged from codons 157 to 278 and most of these mutations lay in two “hot spots” (codon 157 in four cancers and codon 248 in three cancers). The majority of p53 mutations, both transversions (seven cancers) and transitions (five cancers), occurred at the G nucleotide of the codons. An analysis of the clinical information indicated that p53 point mutation was frequently observed in heavy smokers with an average Brinkman index score of more than 1000. On the other hand, HPV DNA, type 16 or 18, was detected in a quarter of the laryngeal cancers. Of eleven HPV‐positive cases, nine were immunohistochemically positive for p53, of which four contained a p53 point mutation. These results suggested no inverse relation between p53 mutation and HPV infection in laryngeal cancers. Our study indicates that p53 abnormalities are related to smoking history and the correlation might be better for smoking and chemical mutagenesis than for HPV.

Keywords: p53, Immunohistochemistry, Point mutation, HPV, Laryngeal cancer

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REFERENCES

  • 1. ) Linzer , D. I. H. and Levine , A. J.Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40‐transformed cells and uninfected embryonal carcinoma cells . Cell , 17 , 43 – 52 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Lane , D. P. and Crawford , J. T.antigen is bound to a host protein in SV40‐transformed cells . Nature , 278 , 261 – 285 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Finlay , C. A. , Hinds , P. W. and Levine , A. J.The p53 proto‐oncogene can act as a suppressor of transformation . Cell , 57 , 1083 – 1093 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) McBride , O. W. , Merry , D. and Givol , D.The gene for human p53 cellular tumor antigen is located on chromosome 17 short arm (17pl3) . Proc. Natl Acad. Set. USA , 83 , 130 – 134 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. ) Levine , A. J. , Momand , J. and Finlay , C. A. , The p53 tumour suppressor gene . Nature , 351 , 453 – 456 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Hollstein , M. , Sidransky , D. , Vogelstein , B. and Harris , C. C.p53 mutations in human cancers . Science , 253 , 49 – 53 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Field , J. K. , Spandidos , D. A. , Malliri , A. , Gosney , J. R. , Yiagnisis , M. and 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 , 64 , 573 – 577 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. ) Dolcetti , R. , Doglioni , C. , Maestro , R. , Gasparotto , D. , Barzan , L. , Pastore , A. , Romanelli , M. and 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 , 52 , 178 – 182 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Maestro , R. , Dolcetti , R. , Gasparotto , D. , Doglioni , C. , Pelucchi , S. , Grandi , E. and Boiocchi , M.High frequency of p53 gene alterations associated with protein overexpres‐sion in human squamous cell carcinoma of the larynx . Oncogene , 7 , 1159 – 1166 ( 1992. ). [PubMed] [Google Scholar]
  • 10. ) Somers , K. D. , Merrick , M. A. , Lopez , M. E. , Incognito , L. S. , Schechter , G. L. and Casey , G. , Frequent p53 mutations in head and neck cancer . Cancer Res. , 52 , 5997 – 6000 ( 1992. ). [PubMed] [Google Scholar]
  • 11. ) Anwar , K. , Nakakuki , K. , Imai , H. , Naiki , H. and Inuzuka , M.Over‐expression of p53 protein in human laryngeal carcinoma . Int. J. Cancer , 53 , 1 – 5 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Nakanishi , Y. , Noguchi , M. , Matsuno , Y. , Mukai , K. , Shimosato , Y. and Hirohashi , S.p53 expression in squamous cell carcinoma and dysplasia of the vocal cords and oral cavity . Appl. Immunohistochem , 1 , 101 – 107 ( 1993. ). [Google Scholar]
  • 13. ) Chiba , L. , Takahashi , T. , Nau , M. , D'Amico , D. , Curiel , D. T. , Mitsudomi , T. , Buchhagen , D. L. , Carbone , D. , Piantadosi , S. , Koga , H. , Reissman , P. T. , Slamon , D. J. , Holmes , E. C. and Minna , J. D.Mutations in the p53 gene are frequent in primary, resected non‐small cell lung cancer . Oncogene , 5 , 1603 – 1610 ( 1990. ). [PubMed] [Google Scholar]
  • 14. ) Suzuki , H. , Takahashi , T. , Kuroishi , T. , Suyama , M. , Ariyoshi , Y. , Takahashi , T. and Ueda , R.p53 mutations in non‐small cell lung cancer in Japan: association between mutations and smoking . Cancer Res. , 52 , 734 – 736 ( 1992. ). [PubMed] [Google Scholar]
  • 15. ) Kiyabu , M. T. , Shibata , D. , Arnheim , N. , Martin , W. J. and Fitzgibbons , P. L.Detection of human papillomavirus in Formalin‐fixed, invasive squamous carcinomas using the polymerase chain reaction . Am. J. Surg. Pathoi , 13 , 221 – 224 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Hoshikawa , T. , Nakajima , T. , Uhara , H. , Gotoh , M. , Shimosato , Y. , Tsutsumi , K. , Ono , I. and Ebihara , S.Detection of human papillomavirus DNA in laryngeal squamous cell carcinomas by polymerase chain reaction . Laryngoscope , 100 , 647 – 650 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Perez‐Ayara , M. , Ruiz‐Cabello , F. , Esteban , F. , Concha , A. , Redondo , M. , Oliva , M. R. , Cabrera , T. and Garrido , F.Presence of HPV 16 sequences in laryngeal carcinomas . Int. J. Cancer , 46 , 8 – 11 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Shidara , K. , Suzuki , T. , Kara , F. and Nakajima , T.Lack of synergistic association between human papillomavirus and Ras gene point mutation in laryngeal carcinomas . Laryngoscope , 104 , 1008 – 1012 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Dyson , N. , Howley , P. M. , Munger , K. and Harlow , E.The human papilloma virus‐16 E7 oncoprotein is able to bind to the retinoblastoma gene product . Science , 243 , 934 – 937 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Werness , B. A. , Levine , A. J. and Howley , P. M.Association of human papillomavirus types 16 and 18 E6 proteins with p53 . Science , 248 , 76 – 79 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Crook , T. , Wrede , D. , Tidy , J. A. , Mason , W. P. , Evans , D. J. and Vousden , K. H.Clonal p53 mutation in primary cervical cancer: association with human‐papillomavirusnegative tumours . Lancet , 339 , 1070 – 1073 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Ciechanover , A. , DiGiuseppe , J. A. , Bercovich , B. , Orian , A. , Richter , J. D. , Schwartz , A. L. and Brodeur , G. M.Degradation of nuclear oncoproteins by the ubiquitin system in vitro . Proc. Natl Acad. ScL USA , 88 , 139 – 143 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. ) Busby‐Earle , R. M. C. , Steel , C. M. , Williams , A. R. W. , Cohen , B. and Bird , C. C.Papillomavirus, p53, and cervical cancer . Lancet , 339 , 1350 ( 1992. ). [PubMed] [Google Scholar]
  • 24. ) Tsuda , H. and Hirohashi , S.Frequent occurrence of p53 gene mutations in uterine cancers at advanced clinical stage and with agressive histological phenotypes . Jpn. J. Cancer Res. , 83 , 1184 – 1191 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. ) Goelz , S. E. , Hamilton , S. R. and Vogelstein , B.Purification of DNA from formaldehyde fixed and paraffin embedded human tissue . Biochem. Biophys. Res. Comtmtn. , 130 , 118 – 126 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Shi , S.‐R. , Key , M. E. and Kalra , K.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. , 39 , 741 – 748 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 27. ) Yoshikawa , H. , Kawana , T. , Kitagawa , K. , Mizuno , M. , Yoshikura , H. and Iwamoto , A.Detection and typing of multiple genital human papillomaviruses by DNA amplification with consensus primers . Jpn. J. Cancer Res. , 82 , 524 – 531 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. ) Orita , M. , Suzuki , Y. , Sekiya , T. and Hayashi , K.Rapid and sensitive detection of point mutation and DNA polymorphisms using the polymerase chain reaction . Genomics , 5 , 874 – 879 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 29. ) Miller , C. W. , Simon , K. , Aslo , A. , Kok , K. , Yokota , J. , Buys , C. H. C. M. , Terada , M. and Koeffler , H. P.p53 mutations in human lung tumors . Cancer Res. , 52 , 1695 – 1698 ( 1992. ). [PubMed] [Google Scholar]
  • 30. ) Brinkman , G. L. and Osborne , E.The prevalence of chronic bronchitis in an industrial population . Am. Rev. Respir. Dis. , 86 , 47 – 54 ( 1962. ). [DOI] [PubMed] [Google Scholar]
  • 31. ) Sameshima , Y. , Matsuno , Y. , Hirohashi , S. , Shimosato , Y. , Mizoguchi , H. , Sugimura , T. , Terada , M. and Yokota , J.Alterations of the p53 gene are common and critical events for the maintenance of malignant phenotypes in small‐cell lung carcinoma . Oncogene , 7 , 451 – 457 ( 1992. ). [PubMed] [Google Scholar]
  • 32. ) Wagata , T. , Shibagaki , I. , Imamura , N. , Shimada , Y. , Toguchida , J. , Yandell , D. W. , Ikenaga , M. , Tobe , T. and Ishizali , K.Loss of 17p, mutation of the p53 gene, and overexpression of p53 protein in esophageal squamous cell carcinomas . Cancer Res. , 53 , 846 – 850 ( 1993. ). [PubMed] [Google Scholar]
  • 33. ) Runnerbaum , I. B. , Nagarajan , M. , Bowman , M. , Soto , D. and Sukumar , S.Mutations in p53 as potential molecular markers for human breast cancer . Proc. Natl. Acad. Sci USA. 88 , 10657 – 10661 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34. ) Puisieux , A. , Lim , S. , Groopman , J. and Otzurk , M.Selective targeting of p53 gene mutation hotspots in human cancers by etiologically defined carcinogens . Cancer Res. , 51 , 6185 – 6189 ( 1991. ). [PubMed] [Google Scholar]
  • 35. ) Hsu , I. C. , Metcalf , R. A. , Sun , T. , Welsh , J. A. , Wang , N. J. and Harris , C. C.Mutational hot spot in the p53 gene in human hepatocellular carcinomas . Nature , 350 , 427 – 428 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 36. ) Bressac , B. , Kew , M. , Wands , J. and Ozyurk , M.Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa . Nature , 350 , 429 – 431 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 37. ) Stell , P. M.Smoking and laryngeal cancer . Lancet , i , 617 – 618 ( 1972. ). [DOI] [PubMed] [Google Scholar]
  • 38. ) Wynder , E. L. and Stellman , S. D.Comparative epidemiology of tobacco‐related cancers . Cancer Res. , 37 , 4608 – 4622 ( 1977. ). [PubMed] [Google Scholar]
  • 39. ) Mazur , M. and Glickman , B. W. , Sequence specificity of mutations induced by benzo[a]pyrene‐7,8‐diol‐epoxide at endogenous aprt gene in CHO cells . Somatic Cell Mol. Genet. , 114 , 393 – 400 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 40. ) Chen , R.‐H. , Maher , V. M. and McCormick , J. J.Effect of excision repair by diploid human flbroblasts on the kinds and locations of mutations induced by (+)‐7b,8a‐dihy‐droxy‐9a, 10a‐epoxy‐7,8,9,10‐tetrahydrobenzo[a]pyrene in the coding region of the HPRT gene . Proc. Natl. Acad. Sci USA , 87 , 8680 – 8684 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41. ) Bennet , W. P. , Hollstein , M. C. , Metcalf , R. A. , Welsh , J. A. , He , A. , Zhu , S. , Kusters , L. , Resau , J. H. , Trump , B. F. , Lane , D. P. and Harris , C. C.p53 mutation and protein accumulation during multistage human esophageal carcinogenesis . Cancer Res. , 52 , 6092 – 6097 ( 1992. ). [PubMed] [Google Scholar]

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