Prognostic Value of Tumor Stem Cells and Anaplastic Lymphoma Kinase Expression in Patients with Primary Cutaneous Melanoma

摘要

Melanoma is the most aggressive cutaneous neoplasm. Cancer stem cells (CSCs) may be one of the reasons for the low sensitivity of melanoma to chemotherapy, the short curative effect and the development of resistance to the targeted therapy, as well as the lack of efficiency of immune checkpoint inhibitors and disease relapses. The aim of our the study was to determine the influence of the expression of stem cells markers (ABCB5 и CD133) and tyrosine kinases of mutated Anaplastic Lymphoma Kinase (ALK) genes found in primary tumors on survival of patients with stage I-II cutaneous melanomas. Materials of 48 patients with melanoma were used, and their morphological parameters (tumor thickness, invasion level, lymphoid infiltration) were assessed. The expression of CSCs markers, mutant kinases was determined using the immunohistochemical method. The statistical significance of the influence of the parameters studied on the overall (OS) and 2- year relapse-free (RFS) survival was assessed by calculating the correlation coefficient using the rank method. Stem cell markers were found in 25 (52%) of 48 patients with cutaneous melanomas. ABCB5 was expressed in 20 (54%), CD133 was expressed in 17 (46%) patients. The co-expression of both markers was observed in 12 patients (32%). The 2-year OS in the group with CSC markers expressed (first group) was 76%, whereas in the group w/o such markers expressed (second group), the OS was 91.31%. The rates of RFS also differed between the two groups: in the first, RFS was 80%, and in the second one, it reached 91.31%. CD133 marker was found in 80% of the first group patients with metastases and relapses. A strong correlation was found between the increase percentage of cells expressing CD133 and the increase invasion level. (P=0.879 ±0.107). A strong correlation was found between the increase percentage of cells expressing ABCB5 and the increase tumor thickness. (P=0.943 ±0.088). The expression of mutant ALK was found in 28% of patients with CSC markers detected, and no statistically significant correlation between the prognosis and the presence of ALK was found. ABCB5 and CD133+ are promising markers of tumor stem cells applicable to predicting the clinical course of primary cutaneous melanomas. A correlation between ABCB5 and CD133 markers and a number of morphological parameters shows the importance of their study for understanding the fundamental mechanisms of melanoma carcinogenesis. The inhibition of ABCB5 and CD133+ markers and mutant ALK may serve as a target for the therapy for melanoma in perspective.