Overexpression of p53 protein in basal cell carcinomas of human skin.

Basal cell carcinoma (BCC) of the skin is the most common human cancer, but its molecular-genetic pathogenesis is unclear. In many other types of cancer, mutations of the tumor-suppressor gene p53 occur frequently and may lead to overexpression of a long-lived mutant form of p53 protein. In this study, overexpression of p53 protein was detected immunohistochemically in 30 (83%) of 36 specimens of BCC of the head and neck. The same regions of tumor typically were reactive both with a monoclonal antibody (PAb240) specific for the mutant protein and with one (PAb1801) directed against an epitope common to both wild-type and mutant p53 protein. Keratinocytes of chronically sun-exposed epidermis adjacent to BCCs also focally overexpressed p53 protein in the majority of cases, whereas those of sun-protected buttock skin did not. Mutation of p53 may form an important part of the pathogenetic sequence in a majority of cases of BCC.

[1]  H P Koeffler,et al.  P53 mutations in human cancer. , 1993, Leukemia.

[2]  C Zugerman,et al.  Diagnosis and management of skin cancer. , 1991, Comprehensive therapy.

[3]  J. Simon,et al.  A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[4]  A. Harris,et al.  Expression of mutant p53 in melanoma. , 1991, Cancer research.

[5]  M. Weinstock,et al.  Nonmelanoma skin cancer mortality. A population-based study. , 1991, Archives of dermatology.

[6]  T. Tong,et al.  Cancer statistics, 1991 , 1991, CA: a cancer journal for clinicians.

[7]  C. Purdie,et al.  p53 expression in colorectal tumors. , 1991, The American journal of pathology.

[8]  F. Mitelman,et al.  Cytogenetic analysis of 33 basal cell carcinomas. , 1991, Cancer research.

[9]  U. Schlegel,et al.  Mutational analysis of the human p53 gene in malignant melanoma. , 1991, Pigment cell research.

[10]  C. Marshall.  Tumor suppressor genes , 1991, Cell.

[11]  O. Halevy,et al.  Different tumor-derived p53 mutants exhibit distinct biological activities. , 1990, Science.

[12]  A. Harris.  Mutant p53—the commonest genetic abnormality in human cancer? , 1990, The Journal of pathology.

[13]  B. Vogelstein,et al.  Suppression of human colorectal carcinoma cell growth by wild-type p53. , 1990, Science.

[14]  O. Halevy,et al.  Conditional inhibition of transformation and of cell proliferation by a temperature-sensitive mutant of p53 , 1990, Cell.

[15]  E. Appella,et al.  Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[16]  D. Lane,et al.  Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. , 1990, The EMBO journal.

[17]  J. Bos,et al.  Ras oncogene mutations in basal cell carcinomas and squamous cell carcinomas of human skin. , 1990, The Journal of investigative dermatology.

[18]  A. Harris,et al.  Increased expression of mutant forms of p53 oncogene in primary lung cancer , 1990, The Lancet.

[19]  G. T. Bowden,et al.  Biological and molecular aspects of radiation carcinogenesis in mouse skin. , 1990, Radiation research.

[20]  D. Lane,et al.  p53: oncogene or anti-oncogene? , 1990, Genes & development.

[21]  R. Sager.  Tumor suppressor genes: the puzzle and the promise. , 1989, Science.

[22]  F. Collins,et al.  Mutations in the p53 gene occur in diverse human tumour types , 1989, Nature.

[23]  T. Pawson,et al.  High incidence of lung, bone, and lymphoid tumors in transgenic mice overexpressing mutant alleles of the p53 oncogene , 1989, Molecular and cellular biology.

[24]  A. Levine,et al.  The p53 proto-oncogene can act as a suppressor of transformation , 1989, Cell.

[25]  R. Carroll,et al.  Long-term recurrence rates in previously untreated (primary) basal cell carcinoma: implications for patient follow-up. , 1989, The Journal of dermatologic surgery and oncology.

[26]  H. Ananthaswamy,et al.  Detection and identification of activated oncogenes in human skin cancers occurring on sun-exposed body sites. , 1988, Cancer research.

[27]  Y. Ogiso,et al.  Expression of proto-oncogenes in normal and tumor tissues of human skin. , 1988, The Journal of investigative dermatology.

[28]  S. Benchimol,et al.  Immortalization of rat embryo fibroblasts by the cellular p53 oncogene. , 1988, Oncogene.

[29]  F. Rilke,et al.  P53 expression in breast cancer , 1988, International journal of cancer.

[30]  T. Slaga,et al.  Malignant progression of papilloma‐derived keratinocytes: Differential effects of the ras, neu, and p53 oncogenes , 1988, Molecular carcinogenesis.

[31]  L. Banks,et al.  Isolation of human-p53-specific monoclonal antibodies and their use in the studies of human p53 expression. , 1986, European journal of biochemistry.

[32]  L. Crawford,et al.  Characterization of the human p53 gene , 1986, Molecular and cellular biology.

[33]  M. Isobe,et al.  Localization of gene for human p53 tumour antigen to band 17p13 , 1986, Nature.

[34]  D. Givol,et al.  The gene for human p53 cellular tumor antigen is located on chromosome 17 short arm (17p13). , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[35]  W. Hiddemann,et al.  DNA Aneuploidy — A Common Cell Marker in Human Malignancies and Its Correlation to Grade, Stage and Prognosis , 1985 .

[36]  J. Jenkins,et al.  The cellular oncogene p53 can be activated by mutagenesis , 1985, Nature.

[37]  A. Levine,et al.  Two distinct mechanisms regulate the levels of a cellular tumor antigen, p53 , 1983, Molecular and cellular biology.