Markers of cell proliferation and expression of melanosomal antigen in lymphangioleiomyomatosis

Pulmonary lymphangioleiomyomatosis (LAM), a disease of young women, is char acterized by proliferation of immature-appearing smooth-muscle cells (LAM c ells) in the lungs and abdomen. LAM cells react with monoclonal antibody HM B45, which recognizes a 100-kD glycoprotein (gp100) originally found in hum an melanoma cells. We investigated the expression and the subcellular local ization of gp100 in lung tissue from patients with LAM and in human melanom a cell lines (Malme-3M, A2058, and CHL-1), and the relationship between thi s expression and cellular proliferation. Binding sites for HMB45 antibody i n melanoma and LAM cells were located in cytoplasmic granules resembling im mature melanosomes. LAM cells reactive for proliferating-cell nuclear antig en (PCNA), a marker of cellular proliferation, were spindle-shaped, in cont rast to the large, epithelioid cells reacting with HMB45 antibody. In accor d with this finding, we observed an inverse relationship between the immuno staining for HMB45 antibody and PCNA in LAM and melanoma cells. Thus, LAM a nd melanoma cells are heterogeneous with respect to their stages of prolife ration and their expression of melanoma antigens. PCNA-positive cells, whic h are more likely to be negative for reactivity with HMB45 antibody, may be more relevant to the progression of LAM than are HMB45-positive cells, whi ch are the hallmark of LAM.