DNA ploidy, p53 expression, and cellular proliferation in normal epithelium and squamous dysplasia of non-cancerous and cancerous human oesophagi

Ki67 expression, S-phase fraction, p53 immunoreactivity and DNA content were examined in morphologically normal mucosa and squamous dysplasia of both cancerous and non-cancerous human oesophagi in order to understand possible early events in the development of esophageal squamous cell carcinoma. 103 different foci from cancerous esophagi including 17 non-pathological epithelium, 10 mild, 17 moderate and 15 severe dysplasia, 14 intraepithelial carcinomas and 30 invasive squamous cell carcinomas were examined. Also studied were 57 biopsy specimens from cancer-free individuals, including 12 normal epithelia, 15 oesophagitis, and 16 mild, 11 moderate and 3 severe dysplasia. Areas of squamous dysplasia from both cancer-free and cancerous oesphagi were morpholgically indistinguishable and both demonstrated increased cellular proliferation compared to normal or non-pathologicol epithelia. However, squamous dysplasia in cancerous oesophagi demonstrated significantly larger Ki67 labelling indices and smaller S-phase fractions than dysplasia in cancer free patients. Squamous dysplasia in cancerous and non-cancerous oesophagi demonstrated a non-diploid DNA histogram in 61.9% and 43.3% respectively. However, dysplasia from cancer- free individuals demonstrated a non-diploid pattern with one or more peaks (Type I non-diploid histogram) and that from oesophageal cancer patients predominantly exhibited non-diploid histograms without any distinctive peaks (Type II non-diploid histogram). Significant differences in the frequency of p53 positive foci were observed between dysplasia of cancer-free (23.3%) and cancerous (56.8%) oesophagi, dysplasia associated with Type II non-diploid histograms had a significantly lalger number of p53-positive foci than those with diploid histograms of Type I non-diploid histograms. These results indicated that the biological features of squamous dysplasia were different between cancerous and non-cancerous human oesophagi despite indistinguishable morphorlogical features. In addition, the combination of p53 immunohistochemistry and DNA ploidy analysis may contribute to identify possible high-risk squamous dysplasia of the oesophagus.