EXPRESSION OF GELATINASE-B AND THE EXTRACELLULAR-MATRIX METALLOPROTEINASE INDUCER EMMPRIN IN BENIGN AND MALIGNANT PIGMENT CELL LESIONS OF THE SKIN

By the degradative effect on basement membrane collagen type IV, matri x metalloproteinases (MMPs) or gelatinases are important in the early invasion of malignant tumors. These enzymes may be released by the tum or cells themselves or may be derived from nearby fibroblasts that hav e been stimulated by the extracellular MMP inducer EMMPRIN. We studied the distribution of 92-kd gelatinase B (MMP-9) and of EMMPRIN in 33 b enign and 41 malignant, paraffin-embedded pigment cell lesions using i mmunohistochemistry and monoclonal antibodies, in benign pigment cell lesions, EMMPRIN but not gelatinase B was expressed in cellular blue n evi whereas all other benign lesions, Including common blue nevi, were negative. In malignant melanomas (MMs), both gelatinase B and EMMPRIN were variably expressed in the pure and invasive radial growth phase but not in the vertical growth phase. All lentigo maligna cases and al l metastatic lesions were negative. Of MMs with thickness < 1.6 mm, 63 % expressed gelatinase B and 70% expressed EMMPRIN, whereas in MMs wit h > 1.6 mm thickness, only 10% expressed gelatinase B and only 25% exp ressed EMMPRIN. We conclude that early invasion of MM is associated wi th ne novo expression of gelatinase B and EMMPRIN by neoplastic melano cytes. Expression of EMMPRIN and MMP-9 may be partly responsible for t he stromal changes observed in thin MM. Their absence in the vertical growth phase and in metastatic lesions suggests that other factors are involved in tissue degradation during later stages of tumor progressi on in MM. The lack of both gelatinase B and EMMPRIN in lentigo maligna may contribute to the indolent behavior of this type of pigment cell lesion.