Notch信号相关受体／配体在皮肤恶性黑素瘤中的表达

Expression of Notch pathway receptors and ligands in cutaneous malignant melanoma

目的 检测Notch信号通路中Notch1、Notch4、Jagged1以及Dll4在皮肤恶性黑素瘤组织中的表达，初步探讨Notch信号通路在黑素瘤发病机制中的作用。方法 免疫组化SP法检测40例恶性黑素瘤及15例色素痣石蜡标本中Notch1、Notch4、Jagged1以及Dll4的表达模式和表达强度。采用SPSS21.0软件进行卡方检验及Spearman秩相关分析。结果 在40例黑素瘤组织（31例阳性表达）及15例色素痣组织（3例阳性表达）Notch1的表达率差异有统计学意义（χ2 = 15.281，P = 0.000），原位（18例）及侵袭性黑素瘤（22例）间Notch1表达强度差异无统计学意义（χ2 = 0.631，P = 0.427）。Notch4、Jagged1以及Dll4的表达率在恶性黑素瘤与色素痣之间差异均有统计学意义（均P 〈 0.05），三者表达强度在原位与侵袭性黑素瘤之间差异亦均有统计学意义（P 〈 0.05）。在黑素瘤组织中，Notch1与Jagged1的表达呈正相关（rs = 0.350，P = 0.027），与Dll4的表达亦呈正相关（rs = 0.562，P = 0.000），但是Jagged1与Dll4的表达呈负相关（rs = -0.734，P = 0.000）。结论 Notch信号通路异常可能是黑素瘤的发病机制之一，但具体作用机制有待进一步研究。

Objective To determine the of Notch pathway receptors （Notch1 and Notch4） and ligands （Jagged1 and Dll4） in cutaneous malignant melanoma （CMM） tissues, and to preliminarily explore the role of the Notch signaling pathway in the pathogenesis of CMM. Methods Immunohistochemical study was performed to determine the pattern and intensity of Notch1, Notch4, Jagged1 and Dll4 in 40 paraffin-embedded CMM specimens and 15 paraffin-embedded pigmented nevus specimens. Statistical analysis was carried out by chi-square test and Spearman rank correlation analysis with the SPSS 21.0 software. Results Notch1 was detected in 31 （77.5%） of 40 CMM specimens, as well as in 3 of 15 pigmented nevus specimens, and the positive rates significantly differed between the two groups （χ2 = 15.281, P 〈 0.001）. However, no significant difference in the intensity of Notch1 was observed between 18 in situ melanoma tissues and 22 invasive melanoma tissues （χ2 = 0.631, P = 0.427）. In addition, the positive rates of Notch4, Jagged1 and Dll4 were also significantly higher in the CMM group than those in the pigmented nevus group （all P 〈 0.05）, and the intensity of Notch4, Jagged1 and Dll4 significantly differed between in situ and invasive melanoma tissues （all P 〈 0.05）. In CMM tissues, the of Notch1 was positively correlated with that of Jagged1 （rs = 0.350, P = 0.027） and Dll4 （rs = 0.562, P 〈 0.001）, while the of Jagged1 was negatively correlated with that of Dll4 （rs = -0.734, P 〈 0.001）. Conclusion Abnormality of the Notch signaling pathway may be involved in the pathogenesis of melanoma, but further researches are still needed to elucidate the detailed mechanism.