Prognostic value of P53 mutations in rectal carcinoma.
The influence of p53 mutations on the response to ionizing radiation and survival was retrospectively evaluated in patients treated with preoperative radiotherapy for rectal carcinoma. From 1989 to 1991, 86 rectal cancer patients treated by preoperative radiotherapy were included in this series. For all patients, endorectal sonography (to define ultrasonography TNM [uTNM]) was performed before treatment; 19 patients were classified as stage 1, 27 as stage 2 and 40 as stage 3. Response to radiotherapy (39 Gy in 13 fractions delivered in 17 days) was assessed by comparing the uT and the T obtained by histologic examination of the resected specimen (TNM classification). A rectal cancer biopsy was performed before treatment and enabled the search for p53 mutations by denaturing gradient gel electrophoresis (DGGE) and sequencing. The status of the p53 gene was correlated with the response to radiotherapy and survival. Forty-nine percent of the tumors presented abnormal DGGE profiles. The prevalence of p53 mutations was significantly higher in patients who did not respond to radiotherapy (63%) than in those who did respond (34%) (p < 0.01). Presence of a p53 mutation was associated with significantly shorter 5-year survival compared to patients without mutations (p < 0.02). In a multivariate analysis, p53 mutation status remained a prognostic factor independent of tumor posttreatment staging (p < 0.05). p53 status is an independent prognostic factor of response to radiotherapy and survival in rectal carcinoma.
INSERM U 434-CEPH, Paris, France.
Christine
C
Rebischung
Jean-Pierre
JP
Gérard
Jacqueline
J
Gayet
Gilles
G
Thomas
Richard
R
Hamelin
Pierre
P
Laurent-Puig
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005091:Exons; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D012004:Rectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
D004273:DNA, Neoplasm