P53 mutational status improves estimation of prognosis in patients with curatively resected adenocarcinoma in Barrett's esophagus.
2000
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
unknown reasons. We reported previously a large multi-institutional
trial implicating p53 mutations as being involved in the pathogenesis
of Barrett’s cancer and representing an early marker for the malignant
potential of Barrett’s epithelium. A prospective study was performed
to evaluate the prognostic impact of p53 mutations on survival in 59
patients with Barrett’s cancer. Tissue for DNA analysis was obtained
by endoscopic biopsy or immediately after surgical resections from the
tumor, Barrett’s epithelium, and normal stomach and esophagus. p53
mutation analysis was performed by PCR-single strand conformational
polymorphism screening of exons 5–9 and DNA sequencing to
unequivocally prove the presence of a mutation. p53 mutations were
identified 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-resections) with cumulative 5-year survival
probabilities of 68.8 ± 9.7% for mutation-negative tumors and
24.3 ± 9.9% for mutation-positive tumors (log rank:
P < 0.001). By Cox proportional hazard analysis,
including the parameters of gender, age, Union International Contre
Cancer tumor stage, grading, and p53 mutation status, only Union
International Contre Cancer tumor stage ( P <
0.0001) and p53 mutation status ( P < 0.02) were of
significant independent prognostic importance. p53 mutation analysis by
DNA sequencing is of significant independent prognostic importance next
to histopathological tumor stage in patients with curatively resected
(RO-resection) Barrett’s cancer. It appears that p53 mutational status
is a valuable parameter to define low-risk (p53 mutation-negative) and
high-risk (p53 mutationpositive) groups for treatment failure
after curative resections.
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