Abnormal activator protein 1 transcription factor expression in CD30-positive cutaneous large-cell lymphomas

Abstract

CD30+ cutaneous large-cell lymphomas (CLCL) represent a heterogeneous subgroup of skin lymphomas including primary cutaneous CD30+ anaplastic large-cell lymphoma (C-ALCL), lymphomatoid papulosis (LyP), transformed mycosis fungoides (T-MF) and Hodgkin's lymphoma (HL) with cutaneous involvement. The activator protein 1 (AP-1) transcription factor consists of JUN, FOS and other protein families. Recent studies have revealed upregulation of JUNB in both MF and C-ALCL and overexpression of JUNB and CD30 in systemic HL and ALCL. To assess systematically the expression pattern of AP-1 transcription factors in CLCL. We analysed paraffin tissue sections from 27 patients with LyP, 10 with C-ALCL, eight with T-MF and two with cutaneous HL by immunohistochemistry with antibodies against c-JUN, JUNB, JUND, c-FOS and RAF-1. We also stained samples from 10 patients with C-ALCL, seven with Sézary syndrome (SS), six with T-MF, three with cutaneous HL, two with LyP and control samples with total and phosphorylated mitogen-activated protein kinase (MAPK) antibodies. Results Positive staining for JUND (++) was observed in 13 cases of LyP (48%), 10 C-ALCL, six T-MF (75%) and two cutaneous HL cases. Positive JUNB protein expression was present in four cases of T-MF (50%), four C-ALCL (44%), three LyP (11%) and two cutaneous HL. Expression of total (p44/42) MAP kinase and phosphorylated p44/42 MAP kinase were detected in nine cases of C-ALCL (90%), seven SS (88%), five T-MF (89%) and three cutaneous HL. Most of these samples also showed positive staining for JUNB. These results suggest the presence of abnormal AP-1 protein expression in CLCL, which may be relevant to CLCL.