Early mycosis fungoides: molecular analysis for its diagnosis and the absence of p53 gene mutations in cases with progression

The histological diagnosis of initial mycosis fungoides (MF) and the molecu lar mechanisms that are responsible for its progression and transformation to the more highly malignant variants of MF remain largely unknown. Because of the ran occurrence of these tumours, the need for snap frozen skin biop sy specimens and the difficulty to obtain suitable material for karyotypic and genotypic analysis, specific cytogenetic and molecular lesions have not yet been identified. In particular the role of known oncogenes and tumour suppressor genes, including the p53 gene, in the pathogenesis and clinical progression of MF has not been extensively investigated. The present study was carried out using the polymerase chain reaction (PCR) technique combine d with temperature gradient err electrophoresis (TGGE) to detect mutations of the p53 gene in 58 patients with MF. TGGE analysis was also used in comb ination with clonality analysis by means of T-cell receptor gamma (TCRG) ge ne rearrangement studies to distinguish parapsoriasis en plaque and initial MF from patch/plaque stags MF. More than 83% of the diagnosis of initial M F could be confirmed using PCR-TGGE analysis: However, Although the sensiti ve TGGE analysis was used for all exons, p53 gene polymorphisms were found in 4 and p53 gene mutation in only of 58 biopsy specimens. It appears unlik ely that p53 gene mutations play a role in either the Pathogenesis of parap soriasis and initial MF or their progression to advanced stages of MF. Howe ver, TCRG gene rearrangement studies by means of TCR-TGGE analysis may be u seful for distinguishing histologically discordant cases of initial MF. (C) 2001 Elsevier Science Ireland Ltd. Ali rights reserved.