Malignant Melanoma – from Classical Histology towards Molecular Genetic Testing

Česká verzia

Authors: A. Ryška ¹; O. Horký ²; J. Berkovcová ²; I. Tichá ³; M. Kalinová ⁴; M. Matějčková ⁵; Á. Bóday ⁶; J. Drábek ⁷; P. Martínek ⁸; J. Šimová ⁹; K. Sieglová ¹; H. Vošmiková ¹
Authors place of work: Fingerlandův ústav patologie, LF UK a FN Hradec Králové ¹; Oddělení onkologické patologie, Masarykův onkologický ústav, Brno ²; Ústav patologie, 1. LF UK a VFN v Praze ³; Ústav patologie a molekulární medicíny, 2. LF UK a FN Motol, Praha ⁴; Oddělení patologie a molekulární medicíny, Thomayerova nemocnice, Praha ⁵; Oddělení lékařské genetiky, Laboratoře AGEL, Nový Jičín ⁶; Laboratoř experimentální medicíny, FN Olomouc ⁷; Bioptická laboratoř, s. r. o., Plzeň ⁸; CGB laboratoř, a. s., Ostrava ⁹
Published in the journal: Klin Onkol 2017; 30(3): 182-189
Category: Přehled
doi: https://doi.org/10.14735/amko2017182

Summary

Background:
Malignant melanoma is – in comparison with other skin tumors – a relatively rare malignant neoplasm with highly aggressive biologic behavior and variable prognosis. Recent data in pathology and molecular diagnostics indicate that malignant melanoma is in fact not a single entity but a group of different neoplasms with variable etiopathogenesis, biologic behavior and prognosis. New therapeutic options using targeted treatment blocking MAPK signaling pathway require testing of BRAF gene mutation status. This helps to select patients with highest probability of benefit from this treatment.

Aim:
This article summarizes information on the correlation of morphological findings with genetic changes, discusses the representation of individual genetic types in various morphological subgroups and deals with the newly proposed genetic classification of melanoma and the current possibilities, pitfalls and challenges in BRAF testing of malignant melanoma. It also describes the current testing situation in the Czech Republic – the methods used, the representation of BRAF mutations in the tested population and the future of testing. It also shows the limitations of the BRAF and MEK targeted treatment concept resulting from the heterogeneity of the tumor population. Mechanisms of acquired resistance to MAPK pathway inhibitors, possibilities of their detection, and issues of combination of targeted therapy and immunotherapy are discussed.

Key words:
malignant melanoma – BRAF – mutation – molecular targeted therapy – tumor microenvironment – tumor heterogeneity

This work was supported by projects PROGRES Q40/11, BBMRICZ LM2015089, SVV 260398 and GACR 17-10331S.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
28. 3. 2017

Accepted:
16. 5. 2017

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