p53 mutational status improves estimation of prognosis in patients with curatively resected adenocarcinoma in Barrett's esophagus

The incidence of adenocarcinomas in Barrett's esophagus has been rising in the last two decades in the United States and Western Europe for yet unknow n reasons, We reported previously a large multi-institutional trial implica ting p53 mutations as being involved in the pathogenesis of Barrett's cance r and representing an early marker for the malignant potential of Barrett's epithelium. A prospective study was performed to evaluate the prognostic i mpact of p53 mutations on survival in 59 patients with Barrett's cancer. Ti ssue for DNA analysis was obtained by endoscopic biopsy or immediately afte r surgical resections from the tumor, Barrett's epithelium, and normal stom ach and esophagus, p53 mutation analysis was performed by PCR-single strand conformational polymorphism screening of exons 5-9 and DNA sequencing to u nequivocally prove the presence of a mutation. p53 mutations were identifie d in 30 of 59 (50.8%) patients. The presence of a p53 mutation in the tumor had a significant impact on survival after curative resections (RO-resecti ons) with cumulative 5-year survival probabilities of 68.8 +/- 9.7% for mut ation-negative tumors and 24.3 +/- 9.9% for mutation-positive tumors (log r ank: P < 0.001), By Cox proportional hazard analysis, including the paramet ers of gender, age, Union International Contre Cancer tumor stage, grading, and p53 mutation status, only Union International Contre Cancer tumor stag e (P < 0.0001) and p53 mutation status (P < 0.02) were of significant indep endent prognostic importance. p53 mutation analysis by DNA sequencing is of significant independent prognostic importance next to histopathological tu mor stage in patients with curatively resected (RO-resection) Barrett's can cer. It appears that p53 mutational status is a valuable parameter to defin e low-risk (p53 mutation-negative) and high-risk (p53 mutation-positive) gr oups for treatment failure after curative resections.