Expression of Notch pathway receptors and ligands in cutaneous malignant melanoma

Abstract

Objective To determine the expression 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 expression 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 expression 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 expression intensity of Notch4, Jagged1 and Dll4 significantly differed between in situ and invasive melanoma tissues (all P < 0.05) . In CMM tissues, the expression 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 expression 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. Key words: Nevi and melanomas; Receptors, Notch; Immunohistochemistry; Jagged1; Dll4