Expression of p53 and mdm2 mRNA and protein in colorectal carcinomas

The aim of our study was to investigate the expression of p53 and mdm2 mRNA and protein in colorectal adenocarcinoma. For the detection of mRNA, 60 fr esh frozen human tumour samples and 12 samples of corresponding normal tiss ue were examined. After total RNA extraction, reverse transcription (RT) wa s performed followed by cDNA amplification with specific primers using RT-p olymerase chain reaction (PCR). Immunohistochemical detection of protein wa s examined in 81 formalin-fixed and paraffin-embedded human tumour specimen s as well as 15 samples of adjacent normal colorectal tissue. p53 mRNA was detected in 80% (48/60) of the tumours and in 67% (8/12) of normal tissue s amples; 87% (52/60) of tumours had mdm2 mRNA in contrast to only 17% (2/12) of normal tissue specimens. Nuclear p53 protein expression was observed in 52% (42/81) of the tumour specimens and in none of the 15 normal specimens , whereas mdm2 protein was found in the nucleus (31%, 25/81) and also in th e cytoplasm (86%, 70/81) of tumour samples. In normal tissue, mdm2 protein expression was only observed in the cytoplasm (13%, 2/15) and not in the nu cleus. There was a significant correlation between coexpression of p53 and mdm2 protein and the occurrence of lymph node metastases (P = 0.03) as well as between p53 protein expression and the occurrence of distant metastases (P = 0.007). Additionally, significant associations were found between p53 mRNA and p53 protein, p53 mRNA and mdm2 mRNA or protein, and also between mdm2 mRNA and mdm2 protein expression, supporting the existence of a regula tory mechanism involving p53 and mdm2. (C) 1999 Elsevier Science Ltd. All r ights reserved.