Abstract
Cutaneous T-cell lymphoma (CTCL) represents a spectrum of diseases characterized by the accumulation of clonal lymphocytes in the skin. It has been well established that primary cutaneous lymphomas of T-cell lineage have shown ALK protein expression. Furthermore, we have previously shown that ALK-ALCL cell lines highly express the coxsackie-adenovirus receptor (CAR), primary receptor for recombinant wild type-fiber adenovirus-derived vectors for gene therapy. Since skin-directed therapies are the preferred first-line treatment the presence of CAR in CTCL may be helpful in developing therapeutic modalities such gene or targeted molecular therapy. By using ALK-immunostaining, we analyzed retrospectively a series of human tissue primarily diagnosed as CTCL [5 mycosis fungoides (MF), 4 (ALCL)] or peripheral T cell lymphoma (1 PTCL) in order to establish the level of CAR expression in primary CTCL tissue. Fluorescence in situ hybridization (FISH) analyses were also performed on these cases using a locus specific DNA probe for the ALK/p2 locus. We used ALK identification because at the time when the primary diagnosis was placed, the samples were not tested for ALK expression. Patients ranged in age from 32–73 years old with a median age of 58. Normal skin biopsies from 8 patients were used as controls. The results of our analysis are illustrated in Table 1.
TABLE 1. DIAGNOSIS SPECIMEN CAR INTENSITY/% ALK INTENSITY/% FISH CD30 ALCL RT ANKLE MASS 0 / 0 N/A N/A POS ALCL RT FLANK MASS 1+/ 80 1+ / 80 32% B-ANEUPLOID ALCL SKIN, LOWER RIGHT EXTREMITY 0 / 0 2+/ 10 NL POS PTCL SKIN, RT ARM 3+ / 95 3 +/ 70 MF SKIN, RT AXILLA 1 + / 5 3+ / 5 ALK POS MF SKIN 1+ / 5 3+ / 5 NL 21% ANEUPLOID MF SKIN, ARM 0 / 0 3+ / 90 NL (18% ANEUPLOID) POS (RARE) MF SKIN, LEFT BACK 2+ / 40 3+ / 95 NL MF SKIN, RT FOREARM 2+ / 30 1 + / 30
In this study, we show that the immunostaining of CAR in combination with classic ALK-immuno or ALK-FISH is feasible and helps in identifying CTCL cases candidate for skin targeted adenoviral-mediated gene therapy.
Two Decades of Molecular Therapy and a 35-Year Personal View of Changes in Gene Therapy
