CD40 IS A PROGNOSTIC MARKER IN PRIMARY CUTANEOUS MALIGNANT-MELANOMA

CD40 is a receptor at the surface of B lymphocytes with important func tions in the immune response. CD40 hers also been found on a variety o f carcinoma and melanoma cell lines where it has been suggested to ser ve as a possible receptor for mitogenic signals. We studied the expres sion and distribution of CD40 in paraffin sections of 71 uniformly tre ated malignant melanomas (MMs) with a long clinical follow-up using we ll known monoclonal antibodies. For comparison, 71 benign nevi were al so studied. Common acquired nevi occasionally expressed CD40 in nests or single cells at the dermo-epidermal junction; no immunoreactivity w as observed in the dermal part of acquired nevi, and all Spitz' nevi w ere entirely negative One-third of large congenital nevi expressed CD4 0 in small clusters of heavily pigmented, epithelioid cells, correspon ding to so-called proliferative nodules. In 41 of 71 MMs, CD40 was exp ressed in single or clustered neoplastic melanocytes; 3 cases showed C D40 expression only in the radial growth phase, and in 32 cases, the v ertical growth phase showed CD40 expression. The same staining pattern was obtained with other anti-CD40 monoclonal antibodies, directed to different epitopes of the CD40 molecule. In 29 of 32 MMs showing CD40 in the vertical growth phase, expression of the CD40 ligand (CD40L) wa s studied in 13 of these 29, CD40L was found in the same tumor areas t hat expressed CD40. Analysis of 28 metastases from 24 MM patients show ed in the majority of cases a similar, scattered or nodular staining p attern as observed in the primary tumor. Patients expressing CD40 in t he vertical growth phase of their MM did not differ significantly from CD40-negative patients with respect to any of the known prognostic pa rameters but showed a significantly shorter tumor-free survival. Patie nts with CD40(+) CD40L(+) MM tended to have a shorter tumor-free survi val than those lacking CD40L. We conclude that CD40 represents a novel prognostic parameter in primary cutaneous MM. The co-localization of CD40 and CD40L suggests an autocrine growth loop in the vertical growt h phase of MM.