The melanocyte-specific gene Melastatin (MLSN1) shows an inverse correlation of
mRNA expression with metastatic potential in human and murine cell lines in vitro. Melastatin
mRNA expression in primary cutaneous
melanoma also has been found to correlate with disease-free survival. The histologic patterns of Melastatin
mRNA expression in
nevi, primary
melanoma, and
melanoma metastases have not been described previously. Using in situ hybridization with (35)S-labeled probes, we examined Melastatin
mRNA expression in 64 cases of normal skin, benign
melanocytic nevi, primary cutaneous
melanomas, and
melanoma metastases. Ubiquitous melanocytic expression of Melastatin
mRNA was observed in all benign melanocytic proliferations (14 of 14), although some
nevi showed a gradient of reduced Melastatin expression with increased dermal depth (3 of 14). Uniform expression of Melastatin
mRNA was observed in 49% of primary cutaneous
melanomas (18 of 37 cases, including 1 case of in situ
melanoma). Melastatin
mRNA loss by a portion of the
melanoma was identified in 53% of the invasive
melanoma samples (19 of 36) and 100% of the
melanoma metastases (11 of 11). Primary
melanomas without
mRNA loss ranged in thickness from 0.17 to 2.75 mm (median, 0.5 mm; mean, 0.73 mm), whereas
tumors that showed Melastatin
mRNA down-regulation ranged in thickness from 0.28 to 5.75 mm (median, 1.7 mm; mean, 2.13 mm). A focal aggregate or nodule of
melanoma cells without detectable signal was the most commonly observed pattern of Melastatin loss (13 of 19 cases), whereas complete loss of Melastatin
mRNA expression by all of the dermal
melanoma cells was observed in only 4 of the 19 cases. Two invasive
melanomas displayed a scattered, nonfocal pattern of Melastatin
mRNA loss. Of the 11
melanoma metastases examined, 64% displayed focal Melastatin
mRNA loss, and 36% had complete loss of Melastatin
mRNA expression. We observed several patterns of Melastatin
mRNA expression in primary
melanoma that may be distinguished from expression in benign
melanocytic nevi. Melastatin
mRNA expression appears to correlate with melanocytic
tumor progression,
melanoma tumor thickness, and the potential for
melanoma metastasis. HUM PATHOL 31:1346:1356.