P53 Gene Mutation And Overexpression In Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma ( NPC ), one of the common malignant tumors in China, of which the molecular tumori-genetic mechanism remains unclear. With the development of irradiation facilities and techniques, the long-term survival of the NPC patients has been much improved, but nearly half of the patients still die from local failure or distant metastasis. A reasonable and dependable marker for NPC prognosis would be essential to predict the difficult lesions which should be treated with higher doses irradiation or by other means. p53 mutation, the most common genetic change, is important in the carcinogenesis and related to the prognosis of many human cancers. This study was designed to determine whether p53 mutation is involved in the carcinogenesis and p53 over-expression is correlated to radiosensitivity in vivo so far as NPC as clinical parameters are contained. Using DNA sequencing and immuno-histochemical methods, we investigated the p53 mutation and overexpression in 102 archival formalin-fixed and paraffin-embedded NPC specimens. All the patients had been treated by conventional irradiation in our hospital from 1979 to 1985. Most patients except 7 were from regions of low NPC incidence in China. We wish to present our oberservations as follows:1. Exons 7 and 8 of p53 gene in 23 NPC specimens were analyzed by DNA sequencing. Mutation was found in 65.2% (15/23) cases. All mutations were G:C—A:T transversions at codon 273, then the arginine encoded by this codon was replaced by histidine. This hot-spot mutation might have been induced by some special, not yet identified carcinogens from the environment. With p53 overexpression in another specimen, the absence of mutation in exons 7 and 8 does not preclude...