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In this study we analysed 47 bladder carcinomas for the presence of DNA-HPV subtypes 6, 11, 16, 18, 31 and 33 by nucleic acid in situ hybridization, and for the abnormal accumulation of p53 protein by immunohistochemistry. HPV DNA was found in 27/47 (57%) bladder carcinomas, with multiple subtypes in 20 cases. In squamous cell carcinoma (SCC), HPV DNA was only detected in the superficial layer of the neoplastic epithelium and was found mainly in the nuclear compartment. In contrast, in transitional cell carcinoma (TCC), HPV DNA was also found in deeper parts of the tumour. In about half the cases it was mainly found in the cytoplasmic compartment. In SCC, the HPV DNA labelling occurred in koilocytic cells, while no such association was found in TCC. Abnormal accumulation of p53 protein was found in 24/47 (51%) carcinomas. p53 positivity was found significantly more often in SCC than in TCC (p = 0.05). Concurrent HPV positivity and abnormal p53 protein accumulation was found in 18 cases, 14 showing the presence of HPV subtypes 16 and/or 18 DNA. The results demonstrate that HPV DNA occurs widely in urinary tract tumours. Unlike in some other carcinomas, there was no inverse relationship between HPV positivity and abnormal p53 protein accumulation in bladder carcinomas. Thus HPV infection may play a role in the pathogenesis of bladder carcinomas by some mechanism other than inactivation of the p53 protein.

The frequency and scale of positive p53 immunohistochemistry in 107 intracranial tumours of different types was studied as a possible prognostic marker using a polyclonal antibody CM-1 which detects both the wild-type and mutated p53 proteins. Fifty of the tumours (46.7%) showed nuclear p53 positivity with different percentages of positive nuclei. The positivity was concentrated in glial tumours of which 52.8% were positive. Forty-two of seventy-four astrocytomas (56.8%), 4 of 12 oligodendrogliomas (33.3%), and 1 of 3 ependymomas (33.3%) showed p53-positive nuclei. Cytoplasmic positivity, found in 25 astrocytomas, was always associated with nuclear positivity. Some p53-positive nuclei were seen in 16.7% of the non-gliomatous tumours, but in all cases p53 positivity was seen in less than 1% of the nuclei. The patients with astrocytomas containing more than 5% p53-positive nuclei were younger (mean 27.3 years) (p = 0.016) and their tumours larger in diameter (mean 4.4 cm) (p = 0.05) than those with p53-negative astrocytomas (mean 41.0 years and mean 3.3 cm, respectively). In p53-positive (> or = 1% of nuclei) grade IV astrocytomas, survival time was significantly shorter (mean 7.2 months) than in p53-negative grade IV astrocytomas (mean 15.5 months (p = 0.024). The results indicate frequent p53 expression in intracranial tumours, especially in gliomas. The association of p53 positivity with young age, larger tumour size, and poor prognosis in high-grade astrocytomas suggests that p53 may be involved in the development of more aggressive types of intracranial tumours. According to these results, p53 immunohistochemical positivity may serve as a prognostic marker in high-grade astrocytomas.