Is the p53 inactivation frequency in squamous cell carcinomas of the head and neck underestimated? Analysis of p53 exons 2-11 and human papillomavirus 16/18 E6 transcripts in 123 unselected tumor specimens.

Mutations and interaction with high-risk human papillomavirus (HPV) E6 oncoprotein are well-established mechanisms of p53 inactivation. In a series of 123 unselected squamous cell carcinomas of the head and neck (SCCHN), we performed sequence analysis of the entire coding region of p53 transcript and determined the presence of the E6 transcripts of HPV 16 and 18. Aberrant p53 transcripts were identified in 97 (79%) SCCHN. HPV 16 and/or 18 E6 transcripts were detected in 37 (30%) tumor specimens, including 20 (77%) of the 26 p53 wild-type tumors. The likely inactivation of p53 in 117 (95%) of the 123 SCCHN suggests that this event could be obligatory in the multistep process of carcinogenesis.

[1]  Irene M. Leigh,et al.  Role of a p53 polymorphism in the development of human papilloma-virus-associated cancer , 1998, Nature.

[2]  D. Sidransky,et al.  Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. , 2000, Journal of the National Cancer Institute.

[3]  R. Gilbert,et al.  Patterns of p53 gene mutations in head and neck cancer: full-length gene sequencing and results of primary radiotherapy. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[4]  M. Baumann,et al.  Splicing Mutations in TP53 in Human Squamous Cell Carcinoma Lines Influence Immunohistochemical Detection , 2002, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[5]  Gerard I. Evan,et al.  Induction of apoptosis in fibroblasts by c-myc protein , 1992, Cell.

[6]  R. Birgander,et al.  Is p53 polymorphism maintained by natural selection? , 1994, Human heredity.

[7]  A. Kropveld,et al.  Sequencing analysis of RNA and DNA of exons 1 through 11 shows p53 gene alterations to be present in almost 100% of head and neck squamous cell cancers. , 1999, Laboratory investigation; a journal of technical methods and pathology.

[8]  T. Sekiya,et al.  Detection of aberrations of the p53 alleles and the gene transcript in human tumor cell lines by single-strand conformation polymorphism analysis. , 1991, Cancer research.

[9]  W. McGuire,et al.  Why do so many prognostic factors fail to pan out? , 2005, Breast Cancer Research and Treatment.

[10]  Michael A. Crawford,et al.  Acknowledgement to the 2000 Reviewers , 2000, Annals of Nutrition and Metabolism.

[11]  F. Bosch,et al.  TP53 DNA contact mutations are selectively associated with allelic loss and have a strong clinical impact in head and neck cancer , 1998, Oncogene.

[12]  D. Fisher The p53 tumor suppressor: Critical regulator of life & death in cancer , 2001, Apoptosis.

[13]  D. Carbone,et al.  p53 as a target for anti-cancer immunotherapy. , 1997, Molecular medicine today.

[14]  Miranda Thomas,et al.  The role of the E6-p53 interaction in the molecular pathogenesis of HPV , 1999, Oncogene.

[15]  S. Soltys,et al.  Human papillomavirus and p53 mutational status as prognostic factors in head and neck carcinoma , 2002, Head & neck.

[16]  C. Prives,et al.  The p53 pathway , 1999, The Journal of pathology.

[17]  L. Gleich,et al.  Molecular genetics of head and neck cancer. , 2002, Cancer control : journal of the Moffitt Cancer Center.

[18]  Thierry Soussi,et al.  Assessing TP53 status in human tumours to evaluate clinical outcome , 2001, Nature Reviews Cancer.

[19]  R. Brown,et al.  p53-oriented cancer therapies: current progress. , 1999, Annals of oncology : official journal of the European Society for Medical Oncology.

[20]  E. Appella,et al.  Generation of T Cells Specific for the Wild-Type Sequence p53264–272 Peptide in Cancer Patients: Implications for Immunoselection of Epitope Loss Variants1 , 2000, The Journal of Immunology.

[21]  S. Franceschi,et al.  How strong and how wide is the link between HPV and oropharyngeal cancer? , 2000, The Lancet.

[22]  C. Harris,et al.  The p53 network in lung carcinogenesis , 2002, Oncogene.

[23]  J. Hickman Apoptosis and tumourigenesis. , 2002, Current opinion in genetics & development.

[24]  T. Carey,et al.  Reliable detection of p53 aberrations in squamous cell carcinomas of the head and neck requires transcript analysis of the entire coding region , 2002, Head & neck.

[25]  B. Têtu,et al.  p53 overexpression in head and neck squamous cell carcinoma: review of the literature. , 1996, European journal of cancer. Part B, Oral oncology.

[26]  Miranda Thomas,et al.  Two Polymorphic Variants of Wild-Type p53 Differ Biochemically and Biologically , 1999, Molecular and Cellular Biology.

[27]  J. Bergh,et al.  Assessment of sequence-based p53 gene analysis in human breast cancer: messenger RNA in comparison with genomic DNA targets. , 1998, Clinical chemistry.

[28]  D. Machin,et al.  Prognostic Factor Studies , 2005 .