EXPRESSION OF NUCLEAR MATRIX METALLOPROTEINASE-2 IN PATIENTS WITH CUTANEOUS MELANOMA DEPENDING ON THE AVAILABILITY OF MUTATIONS IN THE PPP6C GENES


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Abstract

Material and metods. Tumor samples from paraffin blocks of melanoma patients obtained from Krasnoyarsk Territorial Oncologic Center were used in the study. Skin tissue samples (n = 40) were received from the Krasnoyarsk Territorial Pathological Anatomy Bureau. The mutation in the exon 7 of the PPP6C gene was determined by the Sanger sequencing method using specific primers. Immunohistochemistry was performed based on a standard technique using primary anti-matrix metalloproteinase-2 antibodies. Results. Mutations in the gene PPP6C were detected in 12.5% of patients; in all patients with mutation, missense mutations were observed: G266R, I271N, P259H, and a combination of two mutations in the hot spots of the P259L and R264L gene were also determined. It was found that the expression of MMP-2 in patients with a PPP6C mutant tumor type was not similar to a wild type tumor patients (p = 0.72). The predominant expression of nuclear MMP-2 is observed in PPP6C-negative patients, while in patients with mutations in the PPP6C gene, the cytoplasmic expression of MMP-2 was predominant (p = 0.045). We also found a predominance of nuclear MMP-2 expression, as a prognostically unfavorable factor, for patients in the PPP6C of negative group. Both of these facts may be related to the fact that this mutation does not affect other signaling mechanisms not associated with the BRAF and NRAS genes, nor does it directly affect the expression pattern of MMP-2.

About the authors

Maria B. Aksenenko

Department of Pathophysiology, Krasnoyarsk State Medical University n.a. prof. V.F. Voyno-Yasenetsky

Email: aksenenko_mariya@mail.ru
MD, PhD, docente, Department of Pathophysiology with a Course of a Clinical Pathophysiology, Krasnoyarsk State Medical University of prof. V.F. VoynoYasenetsky, Krasnoyarsk, 660022, Russian Federation Krasnoyarsk, 660022, Russian Federation

T. G Ruksha

Department of Pathophysiology, Krasnoyarsk State Medical University n.a. prof. V.F. Voyno-Yasenetsky

Krasnoyarsk, 660022, Russian Federation

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