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

Abstract

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/poorlydifferentiated 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. Oesophageal squamous cell carcinoma is one of the most common human cancers world-wide (Parkin et al., 1988). The incidence and mortality rate is particularly high among Chinese populations, i.e., in Hong Kong (Lee, 1991). Despite various therapeutic interventions, including surgery, radiotherapy, and chemotherapy, the 5-year survival rate for this disease remains low (Law et al., 1992). Thus, to improve therapeutic and preventive interventions, a biological understanding of the nature of the disease is essential.The p53 gene coding for a 53-kDa nuclear phosphoprotein is believed to be a tumour suppressor gene. It is located on the short-arm of chromosome 17 and is a critical regulator of cell growth, differentiation and apoptosis through its actions in cellcycle checkpoint control (Greenblatt et al., 1994). It is also well known that mutation of the p53 gene is the most common genetic alteration in human cancers. A number of studies have shown that p53 protein over-expression may provide insight into the carcinogenesis in oesophageal squamous cell carcinomas (Lam et al., 1995b). However, there is lack of well planned molecular studies to correlate p53 mutations with the clinico-pathological parameters (including the survival data) in patients with oesophageal squamous cell carcinomas.In this study, we have analysed the correlation of p53 gene mutations with the clinico-pathological features. The profile of p53 mutations was also studied by DNA sequencing in order to gain insight on the carcinogenesis of oesophageal squamous cell carcinomas in Hong Kong Chinese. MATERIAL AND METHODS Patient characteristicsThe patients who were chosen for our study had resections for oesophageal cancers at some point during the period between July 1990 and June 1994 at Queen Mary Hospital. The selection criteria for this study included primary oesophageal squamous cell carcinomas from Chinese patients;...

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Expression level of beta-catenin is associated with prognosis of esophageal carcinoma

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