Expression of p73, a novel protein related to the p53 tumour suppressor p53, and apoptosis in cholangiocellular carcinoma of the liver.

p73, the first homologue of the tumour suppressor protein p53, was recently discovered on chromosome 1p36 and has been shown to induce apoptosis in a p53-like manner. The present study was performed with the aim of investigating the expression of p53, its new homologue p73 and the occurrence of apoptosis in cholangiocellular carcinoma. Protein levels of p73 were examined in 41 patients with curatively (R0-) resected cholangiocellular carcinomas with an antiserum, raised against a peptide in the N-terminal domain of p73. The incidence of mutations in the p53 gene was analysed by direct sequencing and also immunohistochemically. Apoptotic cell death was assessed using in-situ end-labelling (ISEL) technique in combination with morphological criteria. The results obtained were correlated with patient survival. Immunostaining of p73 protein was detected in 17/41 carcinomas examined (41%). The immunoreactivity was confined to the cell nucleus. In 15/41 patients (37%), mutations of the p53 gene were observed. Eleven out of these 15 patients stained also positive for p73. In contrast, out of 26 patients without any detectable p53 mutation, only six exhibited p73 immunostaining. We failed to observe a correlation between p73 expression or p53 and apoptosis within a given tumour. Survival analysis including the parameters stage and grade of disease, p73 and p53, and also apoptosis, showed that tumour stage and grade as well as p53 and p73 were significantly related to prognosis. In Cox regression survival analysis, however, only extent of primary tumour and lymph node status had an independent prognostic impact. Our results with a high prevalence of p73 within tumours harbouring mutated p53 gene suggest that p73 could compensate for p53 function. We failed to establish p73 or p53 as independent prognostic factors in cholangiocellular carcinoma of the liver.