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Frequent p53 Mutations at Dipyrimidine Sites in Patients with Pyothorax-associated Lymphoma¹

Departments of Radiation Biology [T. H., M. K., E. T., T. N.] and Pathology [K. A.], Faculty of Medicine, Osaka University, Osaka 565-0871; Department of Surgery, National Kinki Chuo Hospital, Osaka 591-8025, [K. I.]; and Department of Surgery, Research Institute of Tuberculosis, Tokyo 204-0022, [Y. N.], Japan

A high incidence of non-Hodgkin's lymphoma of the pleural cavity has developed in Japanese patients with long-standing pyothorax (38 years on average) resulting from artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis. Patients with pyothorax-associated lymphoma (PAL) have long been exposed to antituberculous drugs, antibiotics, bacterial or viral products, and frequent diagnostic radiation for the confirmation of pneumothorax and pyothorax. We analyzed p53 mutations on paraffin-embedded specimens from 21 patients with PAL by PCR-single-strand conformational polymorphism followed by direct sequencing. An unusually high frequency of p53 mutations (14 of 21 cases, 67%) was detected in the PAL specimens, and mutations consisted of 13 nucleotide substitutions and 1 deletion. Furthermore, 10 of 13 substitutions (77%) occurred at dipyrimidine sites (CC:GG to CT:GA substitution). Such specificity has not been reported, except for solar light-related skin cancer and AIDS-related lymphoma in some parts. An UV light mimetic agent may be produced in the long history of chronic inflammation in tuberculosis or immunodeficient patients.

¹ Supported by a grant from the Japanese Ministry of Education, Science, Sports and Culture.

² To whom requests for reprints should be addressed, at Department of Pathology, Faculty of Medicine, Osaka University, 2-2 Yamada-Oka, Suita, Osaka 565-0871, Japan. Phone: 81-6-879-3710; Fax: 81-6-879-3713.

Received 12/30/97. Accepted 1/26/98.

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