Activated leukocyte cell adhesion molecule/CD166, a marker of tumor progression in primary malignant melanoma of the skin

Abstract

Expression of activated leukocyte cell adhesion molecule (ALCAM)/CD166 correlates with the aggregation and metastatic capacity of human melanoma cell lines (Am J Pathol 1998, 152:805-813). Immunohistochemistry on a series of human melanocytic lesions reveals that ALCAM expression correlates with melanoma progression. Most nevi (34/38) and all thin melanomas studied (Clark levels I and II) did not express ALCAM. In contrast, immunoreactivity was detected in the invasive, vertical growth phase of 2 of the 13 Clark level III lesions tested. The fraction of positive lesions further increased in Clark level IV (13/19) and in Clark level V (4/4) lesions. ALCAM expression was exclusively detectable in the vertical growth phase of the primary tumor. In melanoma metastases, approximately half of the lesions tested (13/28) were ALCAM positive. According to the Breslow-thickness, ALCAM expression was observed in less than 10% of the lesions that were thinner than 1.5 mm and in over 70% of the lesions that were thicker than 1.5 mm. Our results strongly suggest that ALCAM plays an important role in melanocytic tumor progression and depict it as a new molecular marker for neoplastic progression of primary human melanoma.

Figure 1.

ALCAM-immunoreactivity in frozen sections of normal skin (a), benign nevi (b–d), primary MM (e–h), and metastatic melanoma (i–k). a: Normal skin. ALCAM is expressed by the inner sheath of the hair follicle, the arrector pili muscle, small nerve fibers, and a subset of cells in the acini of eccrine sweat glands. b: Dermal nevocellular nevus lacking ALCAM immunoreactivity; positivity is restricted to small nerve fibers in between the nevus cells. c: Dermal nevocellular nevus showing weak, granular ALCAM staining in areas of neuroid metaplasia but not in regular nevus cells. d: The nevus cell nests in this cellular blue nevus show both membranous and cytoplasmic ALCAM expression (arrowheads); in addition, a small nerve fiber is stained. e: Superficial spreading MM. RGP lacking ALCAM immunoreactivity. f: Superficial spreading MM in RGP and VGP. Whereas the RGP is negative, intense ALCAM expression occurs in the VGP. g and h: High-power view of neoplastic melanocytes in the VGP of a Clark IV and Clark V MM, respectively. g: ALCAM expression is distinctly membranous. h: ALCAM expression occurs predominantly at sites of contact with adjacent neoplastic cells and not at sites of tumor cell-stroma interaction (arrowheads). i and j: Serial sections of a lymph node metastasis of MM. i: The metastatic MM cells exhibit diffuse expression of ALCAM. j: No immunoreactivity is seen when anti-ALCAM antibody is preabsorbed with an excess of recombinant ALCAM. k: Metastatic MM in a lymph node. showing scattered ALCAM positive neoplastic cells. Three-step avidin-biotin complex technique, counterstained with Harris’ hematoxylin; original magnifications, ×88 (a–f, i–k) and ×219 (g, h).