Reduced expression of CDKN2a/p16(INK4a) in mycosis fungoides

Alterations in the CDKN2a gene have been demonstrated in a wide range of hu man tumors including hematopoietic malignancies. To verify whether altered CDKN2a expression is involved in the pathogenesis of mycosis fungoides (MF) , we examined mRNA expression in 20 patients with MF by RT-PCR and dot blot hybridization. CDKN2a mRNA expression was undetectable in 5 of the 20 pati ents (25%), intermediate in 13 (65%) and high in 2 (10%). Immunohistochemic al studies, which were performed in ten patients, revealed that in the four patients showing no mRNA, p16(INK4a) was expressed in < 1% of neoplastic l ymphocytes whereas in the four patients with an intermediate mRNA level, sp ecific nuclear staining was present in 1-25% of tumor cells. In the two pat ients with high levels of CDKN2a mRNA, > 25% of neoplastic lymphocytes stai ned positively. No direct correlation between clinicopathological and molec ular findings was evident in our patients, DNA mutational analysis revealed no alterations in a total of six patients examined, Our results indicate t hat the lack of CDKN2a expression, as found in 25% of the patients, may hav e a pathogenetic role in MF even though the absence of CDKN2a mRNA was not associated with point mutations or minor gene deletions.