OVEREXPRESSION OF P53 PROTEIN IN CUTANEOUS T-CELL LYMPHOMA - RELATIONSHIP TO LARGE-CELL TRANSFORMATION AND DISEASE PROGRESSION

The molecular mechanisms by which advanced cases of cutaneous T cell l ymphoma (CTCL) (mycosis fungoides/Sezary syndrome) undergo large cell transformation (LCT) and develop the morphologic appearance of a large cell lymphoma, are undefined. We used immunohistochemical analysis an d polymerase chain reaction/single strand conformational polymorphism to examine whether p53 mutations are associated with disease progressi on and LCT in CTCL. p53 protein immunohistochemistry was performed on 37 paraffin embedded biopsies from 27 patients with CTCL; LCT was pres ent in 15 biopsies. Overexpression of p53 protein was found in 11 of 3 7 CTCL biopsies including 10 of 15 biopsies (67%) with LCT in which p5 3 staining was predominantly seen in large transformed cells. In contr ast, p53 immunostaining was found in only one of 22 CTCL biopsies with out LCT (p < 0.0004). Serial biopsies revealed acquisition of p53 expr ession following I;CT in two patients in whom initial diagnostic biops ies without LCT were p53 negative by immunostaining. All p53 protein p ositive biopsies were from advanced lesions (cutaneous tumors or extra cutaneous sites); none of 12 patch/plaque stage CTCL biopsies demonstr ated p53 staining. Polymerase chain reaction/single strand conformatio nal polymorphism and sequencing analysis of p53 exons 4-8 was performe d in 11 cases where frozen tissue was available. No mutations were det ected in six cases positive for p53 protein expression. These results suggest overexpression of p53 protein in LCT and disease progression o f CTCL by a mechanism other than p53 gene mutation, in most cases.