P53 AND RAS GENE-EXPRESSION IN HUMAN ESOPHAGEAL CANCER AND BARRETTS EPITHELIUM - A PROSPECTIVE-STUDY

To assess potential clinical applications for molecular genetic marker s associated with human esophageal tumorigenesis, ten patients with pr imary esophageal adenocarcinomas were studied prospectively to evaluat e expression of the p53 and H-ras genes. Total RNA was extracted from tumor, Barrett's epithelium, and histologically normal esophageal muco sa obtained at surgical resection, and gene expression investigated by Northern blot analysis. p53 was overexpressed, relative to normal tis sue from the same patient, in seven tumor and six Barrett's specimens, whereas high levels of H-ras were found in only four tumor and one Ba rrett's specimen. Clinical correlative data were obtained for all pati ents, with a median follow-up of 14 months. Advanced pathologic stage was associated with poor survival. No association was found between ge ne expression and outcome. Three patients with low p53 and H-ras level s developed metastatic disease 7 to 12 months following resection. We conclude that both p53 and ras are implicated in the progression of Ba rrett's epithelium to invasive cancer, and that further clinical corre lative studies are warranted to evaluate potential clinical applicatio n for such molecular markers.