The significance of abnormalities of p53 expression in lymphoma associated with coeliac disease

Abstract

The aim of this study was to investigate pathological tissue from cases of enteropathy- associated T cell lymphoma (EATL), previously shown to over-express p53 protein, for the presence of p53 mutations with the view of correlating over-expression of the protein with the presence of genetic alterations. Single-stranded conformation polymorphism analysis was used to screen a series of formalin-fixed, paraffin-embedded EATL tissue samples and histologically uninvolved tissue Irom the same patients for the presence of p53 mutations in exons 5-8. DNA sequence analysis was performed on cases showing PCR fragments with mobility shifts to confirm the presence of mutations. Immunohistochemistry was used to assess expression of p53 and related cell cycle regulatory proteins in the same cases. Mobility shifts were detected in 10/29 (34.5%) tumour (T) samples and in 3/20 (15%) samples of adjacent (A) uninvolved tissue. Only 2 samples (1 T and I A sample) showing mobility shifts showed no over-expression of p53. DNA sequence analysis identified the presence of mutations in 3/29 (10%) T samples and in 2/20 (10%) A samples. Additional silent mutations were also detected in 2 T samples from different cases. The DNA sequencing results suggest that p53 over-expression is associated with p53 mutations in a small proportion of EATL cases. An alternative mechanism may be responsible for the stabilisation of p53 protein in the remaining cases. The detection of multiple mutations in samples 6om some individual patients may indicate that mutations arise in more than one T cell clone within enteropathic bowel.

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