Prevalence and predictive value of p53 mutation in patients with oesophageal squamous cell carcinomas: a prospective clinico-pathological study and survival analysis of 70 patients.
The tissues from 70 Chinese patients with oesophageal squamous cell carcinoma were prospectively collected to study for the pattern of p53 mutations and its relationship with clinico-pathological features and prognosis using immunohistochemistry, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing. p53 over-expression and p53 mutations were detected in 73% and 44% of the patients. These p53 aberrations had no relationship with the patient age, sex, smoking/drinking habits and tumor site, size or stage. The p53 over-expression was more intense in moderately/poorly-differentiated squamous cell carcinomas. Thirty-three p53 mutations were noted in 31 patients; 18.2% in exon 5, 15.2% in exon 6, 33.3% in exon 7 and 33.3% in exon 8. Mutations were primarily point mutations and common in codons 248, 273 and 285. There were 46% transversions, 36% transitions and 18% frameshift. The survival of the patients depended mainly on the extent of resection. In patients with stage III oesophageal cancer, the median survival of those with p53 mutations was 6.8 months whereas those without was 12.5 months. The results were of clinical importance although the value did not reach statistical significance. Thus, there was a definite role of p53 mutations in the pathogenesis of oesophageal squamous cell carcinomas. p53 mutations were not synonymous with p53 over-expression. The distribution of p53 mutations in oesophageal cancers suggested that the etiologic contribution might be complex and probably involve different exogenous and endogenous exposures. p53 mutations also appear to play a role in predicting the survival of patients with stage III oesophageal squamous cell carcinomas.
Lam
K Y
KY
Department of Pathology, University of Hong Kong. akylam@hkucc.hku.hk
Tsao
S W
SW
Zhang
D
D
Law
S
S
He
D
D
Ma
L
L
Wong
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D016159:Tumor Suppressor Protein p53