Comprehensive Analysis of PTEN in Primary Cutaneous Melanoma

Němejcová, Kristýna; Dundr, P.; Jakša, R.; Bártů, M.; Stružinská, I.; Hojný, J.; Hájková, N.; Kodet, O.

doi:10.14712/fb2020066010007

Folia Biologica > Archive > 2020, Vol. 66 > Issue 1 > Comprehensive Analysis of PTEN in…

Fol. Biol. 2020, 66, 7-16

https://doi.org/10.14712/fb2020066010007

Comprehensive Analysis of PTEN in Primary Cutaneous Melanoma

Kristýna Němejcová¹, P. Dundr¹, R. Jakša¹, M. Bártů¹, I. Stružinská¹, J. Hojný¹, N. Hájková¹, O. Kodet^2,3

¹Institute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
²Department of Dermatology and Venereology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
³Institute of Anatomy, First Faculty of Medicine, Charles University, Czech Republic

Received September 2019
Accepted November 2019

Phosphatase and tensin homologue (PTEN) is a tumour suppressor gene implicated in tumorigenesis of melanoma, with distinct cytoplasmic and nuclear functions. Cytoplasmic PTEN negatively regulates the PI3K/AKT/mTOR signalling pathway, while nuclear PTEN works as a tumour suppressor. Clinical data suggest that the loss of PTEN function in melanoma is associated with aggressive tumour behaviour. We performed a comprehensive analysis of PTEN in 112 primary cutaneous melanomas including immunohistochemical (IHC), fluorescent in situ hybridization (FISH), next-generation sequencing (NGS), and epigenetic analysis. The goal of our study was to: (a) correlate PTEN expression with selected clinico-pathological variables, and assess its prognostic significance; (b) correlate molecular aberrations with PTEN expression to consider the utility of immunohistochemical analysis of PTEN protein expression for screening PTEN genetic alterations; (c) review the literature and evaluate the PTEN expression level in melanoma with respect to possible therapeutic targeting. Our results showed that PTEN molecular alterations were present in 4/20 (20 %) cases with a loss of expression, 3/11 (27 %) cases with clonal-like expression, and 1/81 (1 %) cases with positive PTEN expression. No PTEN promoter methylation was found in any of the cases. Even though the value of our observation is limited by the low number of cases fully evaluated by IHC (112 cases), FISH (19 cases) and NGS (30 cases), our data suggest that IHC is not an appropriate method for the screening of PTEN genetic alterations. Our survival analysis suggests that patients with positive cytoplasmic PTEN expression show better disease-free survival (P < 0.05).

Keywords

melanoma, mutation, deletion, loss of expression, PTEN.

Funding

This work was supported by the Ministry of Health of the Czech Republic (Conceptual development of research organization 64165, General University Hospital in Prague, and project AZV 16-30954A), by Charles University (projects Progress Q28/LF1 and SVV 260367), by the Regional Development Fund (projects BBMRI-CZ No: EF16_013/0001674, and OPPK (Research Laboratory of Tumour Diseases, CZ.2.16/3.1.00/24509). The manuscript is an outcome of the project “Centre for Tumour Ecology – Research of the Cancer Microenvironment Supporting Cancer Growth and Spread” (reg. No. CZ.02.1.01/0.0/0.0/16_019/0000785) supported by the Research, Development and Education Operational Programme.