Expression of monoacylglycerol lipase as a marker of tumour invasion and progression in malignant melanoma

Abstract

Background

Accumulating evidence suggests that the lipid lytic enzyme monoacylglycerol lipase (MAGL) promotes tumour invasion and metastasis through up-regulation of pro-tumourigenic signalling lipids in several tumour cell lines. However, the expression status of MAGL in clinical melanoma tissues and its clinico-pathological significance remain unclear.

Objective

To correlate the tumour expression status of MAGL with the clinico-pathological information of patients with malignant melanoma.

Methods

Polymerase chain reaction (PCR) array screening was performed, and the results were validated using immunocytochemical analysis of tumour and non-tumour melanocytic cell lines. Immunohistochemical staining for MAGL was performed for 74 melanoma samples, including 48 primary and 26 metastatic tumours, in which the expression of MAGL was determined by evaluating the percentage of MAGL-positive tumour cells and the MAGL staining intensity. Finally, we analysed the association of MAGL expression status with tumour progression, tumour thickness and vascular invasion of the primary lesion.

Results

Immunocytochemical analysis revealed that MAGL was expressed in all 12 melanoma cell lines, but not in normal human epidermal melanocytes. In the immunohistochemical analysis, positive staining for MAGL was noted in 32 of 48 (64.5%) primary lesions, 14 of 17 (82.4%) lymph node metastatic lesions and 7 of 9 (77.8%) skin metastatic lesions. Metastatic tumours had a significantly higher staining intensity (p=0.033 for lymph node, p=0.010 for skin). In the analysis of primary lesions, higher MAGL expression correlated with greater tumour thickness (p=0.015) and the presence of vascular invasion (p=0.017). On further evaluation of MAGL-positive primary lesions staining intensity of MAGL tended to be higher in deeper areas of the tumour mass.

Conclusions

The expression of MAGL in tumour cells reflects the aggressiveness of melanoma cells and may serve as a marker of tumour progression.

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