Distinct pronostic value of p53 overexpression and gene alterations in colorectal cancer

Introduction: Pronostic value of ~53 mutations in colorectal cancer (CRC)
is still controversial.
Objective: To assess the short-term prognostic value of p53 protein
overexpression and gene mutation in CRC.
Patients and methods: Between l/96 and 12/98, 512 patients (pts)
were diagnosed with CRC. Among them, 419 had tumor tissue samples
available for genetic tests. The present study is restricted to 126 pts. Mean
age 67 years, 59% were male. Tumors were located in colon 68% and
rectum 32%. Stage was l:li%, ll:40%, lll:36%, IV:13%. Pts with initial
stage IV were excluded. Median of follow up was 25,5 months. Mutations
in ~53 at exons 5-9 were detected by PCWSSCP and sequencing. ~53
protein overexpression was analysed by IHC using antibodies DO-7. Also
mutations in the K-ras oncogene were available. Cox proportional hazards
models were used to assess asociation with disease-free survival and to
estimate hazards ratio and 95% confidence intervals.
Resuttsz Overexpression (0+) in p53 protein was evident in 75% of the
tumours. Mutation (M+) in ~53 gene were founded in 55% of the turnouts.
Agreement between results was: 52% both positive (O+M+) and 14% both
negative (O-M-). Major disagreement was overexpression without mutation:27% (O+M-). Only 6% were mutated and did not overexpressed protein
(O-M+). Overall, ~53 mutations did not associate with worse prognosis
(HR=O.9/0.5-15/j. However, a trend was observed towards shorter survival
in 1umours overexpressing ~53 protein (HR=1.6/0.9-3.00. Discordant cases
(C+M-) showed poorer prognosis than negative concordant (O-M-) HR= 2.1
(0.7-5.8). K-ras mutations were detected in 38% of the cases. Mutations in
K-r@ were independent of ~53 alterations and also showed a trend towards
poorer prognosis, HR=I .3 (0.9-l .9).
Conclusions: This preliminary analysis has shown that prognostic value
of p53 protein overexpression is higher than that of ~53 gene mutations.
In the absence of detected gene alterations f153 protein overexpression
depicts a group of CRC turnours with poorer outcome.