Expression of monoacylglycerol lipase as a marker of tumour invasion and progression in malignant melanoma
Expression of monoacylglycerol lipase as a marker of tumour invasion and progression in malignant melanoma
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DOI：
10.1111/jdv.14455
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发表时间：
2017-12-01
影响因子：
9.2
通讯作者：
Tanese, K.
中科院分区：
文献类型：
--
作者：
Baba, Y.;Funakoshi, T.;Tanese, K.
背景越来越多的证据表明，脂解酶单酰甘油脂肪酶(MAGL)通过上调多种肿瘤细胞系中促肿瘤信号转导脂类来促进肿瘤的侵袭和转移。目的探讨MAGL在临床黑色素瘤组织中的表达状况及其临床病理意义。目的探讨MAGL在恶性黑色素瘤患者中的表达状况与临床病理特征的关系。对74例黑色素瘤标本进行MAGL免疫组织化学染色，其中包括48例原发黑色素瘤和26例转移性黑色素瘤，通过计算MAGL阳性肿瘤细胞百分比和MAGL染色强度来确定MAGL的表达。结果免疫细胞化学分析结果显示，MAGL在12个黑色素瘤细胞系中均有表达，但在正常人表皮黑素细胞中不表达。免疫组织化学染色显示MAGL在48个原发灶中阳性32个(64.5%)，17个淋巴结转移灶中14个阳性(82.4%)，9个皮肤转移灶中7个阳性(77.8%)。转移性肿瘤的染色强度明显高于皮肤(P=0.033，P=0.010)。在原发灶分析中，MAGL高表达与肿瘤厚度增大(P=0.015)和血管侵犯有关(P=0.017)。结论MAGL在肿瘤细胞中的表达反映了黑色素瘤细胞的侵袭性，可作为判断肿瘤进展的指标。
BackgroundAccumulating evidence suggests that the lipid lytic enzyme monoacylglycerol lipase (MAGL) promotes tumour invasion and metastasis through up-regulation of pro-tumorigenic signalling lipids in several tumour cell lines. However, the expression status of MAGL in clinical melanoma tissues and its clinicopathological significance remain unclear.ObjectiveTo correlate the tumour expression status of MAGL with the clinicopathological information of patients with malignant melanoma.MethodsPolymerase 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.ResultsImmunocytochemical 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.ConclusionsThe expression of MAGL in tumour cells reflects the aggressiveness of melanoma cells and may serve as a marker of tumour progression.