Prognostic significance of cancer stem cells and ALK expression in patients with stage I–II cutaneous melanoma

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Abstract

Introduction. Melanoma is the main cause of death in patients with malignant tumors of the skin. While at early stages disease prognosis is relatively favorable, biological characteristics of the tumor can negatively affect patients with this pathology. Cancer stem cells and anaplastic lymphoma kinase (ALK) expression in the presence of translocation of its gene are potential prognostic factors in stage I–II cutaneous melanoma are.

Aim. To evaluate prognostic significance of cancer stem cells (CD133+ and ABCB5+ ) and ALK protein expression in patients with primary stage I–II cutaneous melanoma after surgical and combination treatment.

Materials and methods. The study included 48 patients with stage I–II cutaneous melanoma (30 with superficial spreading type, 18 with nodular type). In all patients, expression of cancer stem cell markers (ABCB5 and CD133) and ALK was immunohistochemically determined. Statistical data analysis was performed using Jamovi (version 2.2.5) software. Follow-up duration was 5 years.

Results. During the 5-year observation period, progression of stage I–II cutaneous melanoma was observed in 12 (25 %) patients. Intensity of ABCB5 and CD133 expression in patients with tumor progression was similar. In patients with melanoma progression, ALK expression was observed in 33.3 % of cases, was absent in 8.3 % (р = 0.034) of cases. Five-year recurrence-free survival in patients with ALK expression was 43 %, without ALK expression – 79 % (р = 0.015). ALK protein expression in the presence of its gene translocation increases progression risk 4.3-fold irrespective of histological type of the tumor (р = 0.025). During the 5-year observation period, death due to stage I–II disease progression was observed in 27.1 % of cases. Intensity of CD133 and ALK expression in cases with fatal outcome and without it was the same. ABCB5+ cancer stem cells were more common in cases of fatal outcome (61.5 % of cases) than in cases without it (34.3 % of cases) (р = 0.085). Five-year overall survival of patients with ABCB5 expression was 56 %, without it – 82 %. The presence of ABCB5 increased the risk of death in patients with localized stages of cutaneous melanoma 3.7-fold irrespective of the presence of CD133 (р = 0.041).

Conclusion. ALK protein expression and presence of ABCB5 cancer stem cells can serve as additional unfavorable prognostic factors in stage I–II cutaneous melanoma.

About the authors

K. S. Titov

S.P. Botkin Moscow Scientific and Clinical Center, Moscow Healthcare Department; Peoples’ Friendship University of Russia

ORCID iD: 0000-0003-4460-9136

5 2nd Botkinsky Proezd, Moscow 125281;  6 Miklukho-Maklaya St., Moscow 117198

Russian Federation

A. A. Markin

Peoples’ Friendship University of Russia; A.S. Loginov Moscow Clinical Scientific Center, Moscow Healthcare Departmen

Author for correspondence.
Email: markinalexander1993@yandex.ru
ORCID iD: 0000-0002-9180-9264

Alexander Andreevich Markin

6 Miklukho-Maklaya St., Moscow 117198; 86 Shosse Entuziastov, Moscow 111123

Russian Federation

G. M. Zapirov

Peoples’ Friendship University of Russia

6 Miklukho-Maklaya St., Moscow 117198

Russian Federation

M. V. Sorokina

S.P. Botkin Moscow Scientific and Clinical Center, Moscow Healthcare Department

ORCID iD: 0000-0002-4436-8101

5 2nd Botkinsky Proezd, Moscow 125281

Russian Federation

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Copyright (c) 2025 Titov K.S., Markin A.A., Zapirov G.M., Sorokina M.V.

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