THE GENE AND PROTEIN P53 IN BRONCHIAL-CAR CINOMA - BIOLOGICAL AND CLINICAL ASPECTS

The p53 gene codes for a nuclear phosphoprotein which is capable of mo dulating the expression of certain genes implicated in the regulation of cell division. The mutation of an allele on the p53 gene with loss of he healthy allele, in different tissues such as lung, larynx, bladd er, liver, skin, colon and breast, which may or may not be exposed to chemical or physical carcinogens (tobacco, radon, ultraviolet, aflatox in BI), is associated with the occurrence of cancer Indeed the mutated p53 protein loses its anti-proliferative properties favouring a de-re gulation of cellular multiplication with the accumulation of genetic a berrations. The homozygous deletion of the p53 gene in germ cells in t he members of certain family cancers (Li-Fraumeni syndrome) leads to a n increased incidence of cancers in the child or young adult. The most frequent mutations of the p53 gene end in a stabilisation of the muta ted protein with immuno-histochemical nuclear marking of the cells car rying such an alteration. In certain patients this stabilisation of th e mutated protein ends in auto-immunisation with anti-p53 serum antibo dies. Bronchial cancer is a cancer of which the mutations of p53 are t he most frequent (45-65% of bronchial cancer) as result of the mutagen ic effect of tobacco smoke. These mutations seem to be associated with a bad prognosis and indeed to chemo-and radiotherapeutic resistance. The early diagnosis of p53 alterations (in dysplastic lesions or tumou rs which are only slightly developed) would enable new therapeutic int erventions in bronchial cancer such as gene therapy or radio-immunothe rapy to either restore the p53 gene to normality or to eliminate the c ells expressing the mutated p53 protein respectively.