TRPM1 (Melastatin-1/MLSN1) mRNA expression in Spitz nevi and nodular melanomas

Abstract

The transient receptor potential cation channel, subfamily M, member 1 (TRPM1/Melastatin-1/MLSN-1) expression has been shown to have prognostic utility in the evaluation of primary cutaneous melanoma. We analyzed a series of spindled and epithelioid cell nevi (Spitz) and primary cutaneous nodular melanomas to determine whether the expression of TRPM1 mRNA may be useful in distinguishing between Spitz nevi and nodular melanomas and to further examine the patterns of TRPM1 mRNA expression in cutaneous melanocytic proliferations. Formalin-fixed, paraffin-embedded tissues from 95 Spitz nevi and 33 nodular melanomas were analyzed for the expression of TRPM1 mRNA by in situ hybridization using 35 S-labeled riboprobes. Ubiquitous melanocytic expression of TRPM1 mRNA was observed in 56 of 95 (59%) Spitz nevi and 4 of 33 (12%) nodular melanomas. Diffusely scattered loss of TRPM1 mRNA was identified in 38 of 95 (40%) Spitz nevi and 2 of 33 (6%) nodular melanomas. Regional loss of the TRPM1 mRNA expression by a significant subset of dermal tumor cells or a complete absence of TRPM1 expression by the dermal tumor was identified in 27 of 33 (82%) nodular melanomas, but only 1 of 95 (1%) Spitz nevi. These findings suggest that the pattern of TRPM1 mRNA expression may be helpful in the differentiation of Spitz nevi and nodular melanomas. Of the 16 patients who experienced metastasis, 15 (94%) had primary tumors that displayed reduced MLSN mRNA expression by all or a part of the dermal tumor.

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…The melastatin subfamily of TRP channels was named after a protein (now called TRPM1) that is highly expressed in benign nevi, including Spitz nevi (Erickson et al, 2009), with reduced expression in primary melanoma and absence of expression in metastatic melanoma (Duncan et al, 1998). These observations led to the suggestion that the TRPM1 gene is a tumor suppressor.…”

Transient Receptor Potential Melastatin 1 (TRPM1) Is an Ion-conducting Plasma Membrane Channel Inhibited by Zinc Ions

“…Since then, it has been established that the expression level of TRPM1 is a clinically useful prognostic marker after diagnosis of melanoma (2)(3)(4). In melanocytes, TRPM1 expression is necessary for the function of endogenous nonselective cation channels with constitutive activity, because experimentally down-regulating TRPM1 expression diminished these currents (5).…”

TRPA1 is functionally expressed in melanoma cells but is not critical for impaired proliferation caused by allyl isothiocyanate or cinnamaldehyde

“…Besides an expression of Ca 2+ -permeable TRPM1 and the cold and menthol receptor TRPM8 (Peier et al 2002), in melanoma cells (Yamamura et al 2008;Deeds et al 2000;Erickson et al 2009), potassium channel activity of K V , K Ca and K IR channels has been described (Allen et al 1997;Artym and Petty 2002;Chantome et al 2009). …”