SOX11, SOX10 and MITF Gene Interaction: A Possible Diagnostic Tool in Malignant Melanoma

Malignant melanoma (MM) is a highly heterogenic tumor whose histological diagnosis might be difficult. This study aimed to investigate the diagnostic and prognostic utility of the conventional pan-melanoma cocktail members (HMB-45, melan-A and tyrosinase), in conjunction with SOX10 and SOX11 immunoh...

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Main Authors: Marius-Alexandru Beleaua, Ioan Jung, Cornelia Braicu, Doina Milutin, Simona Gurzu
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Life
Subjects:
Online Access:https://www.mdpi.com/2075-1729/11/4/281
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author Marius-Alexandru Beleaua
Ioan Jung
Cornelia Braicu
Doina Milutin
Simona Gurzu
author_facet Marius-Alexandru Beleaua
Ioan Jung
Cornelia Braicu
Doina Milutin
Simona Gurzu
author_sort Marius-Alexandru Beleaua
collection DOAJ
description Malignant melanoma (MM) is a highly heterogenic tumor whose histological diagnosis might be difficult. This study aimed to investigate the diagnostic and prognostic utility of the conventional pan-melanoma cocktail members (HMB-45, melan-A and tyrosinase), in conjunction with SOX10 and SOX11 immunohistochemical (IHC) expression. In 105 consecutive cases of MMs and 44 of naevi, the IHC examination was performed using the five-abovementioned markers, along with microphthalmia transcription factor (MITF), S100, and Ki67. Correlation with the clinicopathological factors and a long-term follow-up was also done. Survival analysis was performed with Kaplan–Meier curves and compared with TCGA public datasets. None of the 44 naevi expressed SOX11, but its positivity was seen in 52 MMs (49.52%), being directly correlated with lymphovascular invasion, the Ki67 index, and SOX10 expression. HMB-45, SOX10, and tyrosinase, but not melan-A, proved to differentiate the naevi from MMs successfully, with high specificity. Triple MITF/SOX10/SOX11 co-expression was seen in 9 out of 15 negative conventional pan-melanoma-cocktail cases. The independent prognostic value was proved for the conventional pan-melanoma cocktail (triple positivity for HMB-45, melan-A, and tyrosinase) and, independently for HMB-45 and tyrosinase, but not for melan-A, SOX10, or SOX11. As consequence, to differentiate MMs from benign naevi, melan-A should be substituted by SOX10 in the conventional cocktail. Although the conventional pan-melanoma cocktail, along with S100 can be used for the identification of melanocytic origin of tumor cells and predicting prognosis of MMs, the conventional-adapted cocktail (triple positivity for HMB-45, SOX10, and tyrosinase) has a slightly higher diagnostic specificity. SOX11 can be added to identify the aggressive MMs with risk for lymphatic dissemination and the presence of circulating tumor cells.
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spelling doaj.art-2e2dc16a4d834a4780bce3ce6c868f542023-11-21T13:03:45ZengMDPI AGLife2075-17292021-03-0111428110.3390/life11040281SOX11, SOX10 and MITF Gene Interaction: A Possible Diagnostic Tool in Malignant MelanomaMarius-Alexandru Beleaua0Ioan Jung1Cornelia Braicu2Doina Milutin3Simona Gurzu4Department of Pathology, Clinical County Emergency Hospital, Targu-Mures, Romania, 540139 Targu Mures, RomaniaDepartment of Pathology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, 38 Gheorghe Marinescu Street, 540139 Targu Mures, RomaniaResearch Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, RomaniaDepartment of Pathology, Clinical County Emergency Hospital, Targu-Mures, Romania, 540139 Targu Mures, RomaniaDepartment of Pathology, Clinical County Emergency Hospital, Targu-Mures, Romania, 540139 Targu Mures, RomaniaMalignant melanoma (MM) is a highly heterogenic tumor whose histological diagnosis might be difficult. This study aimed to investigate the diagnostic and prognostic utility of the conventional pan-melanoma cocktail members (HMB-45, melan-A and tyrosinase), in conjunction with SOX10 and SOX11 immunohistochemical (IHC) expression. In 105 consecutive cases of MMs and 44 of naevi, the IHC examination was performed using the five-abovementioned markers, along with microphthalmia transcription factor (MITF), S100, and Ki67. Correlation with the clinicopathological factors and a long-term follow-up was also done. Survival analysis was performed with Kaplan–Meier curves and compared with TCGA public datasets. None of the 44 naevi expressed SOX11, but its positivity was seen in 52 MMs (49.52%), being directly correlated with lymphovascular invasion, the Ki67 index, and SOX10 expression. HMB-45, SOX10, and tyrosinase, but not melan-A, proved to differentiate the naevi from MMs successfully, with high specificity. Triple MITF/SOX10/SOX11 co-expression was seen in 9 out of 15 negative conventional pan-melanoma-cocktail cases. The independent prognostic value was proved for the conventional pan-melanoma cocktail (triple positivity for HMB-45, melan-A, and tyrosinase) and, independently for HMB-45 and tyrosinase, but not for melan-A, SOX10, or SOX11. As consequence, to differentiate MMs from benign naevi, melan-A should be substituted by SOX10 in the conventional cocktail. Although the conventional pan-melanoma cocktail, along with S100 can be used for the identification of melanocytic origin of tumor cells and predicting prognosis of MMs, the conventional-adapted cocktail (triple positivity for HMB-45, SOX10, and tyrosinase) has a slightly higher diagnostic specificity. SOX11 can be added to identify the aggressive MMs with risk for lymphatic dissemination and the presence of circulating tumor cells.https://www.mdpi.com/2075-1729/11/4/281melanoma cocktailimmunohistochemistrySOX11SOX10MITFsurvival
spellingShingle Marius-Alexandru Beleaua
Ioan Jung
Cornelia Braicu
Doina Milutin
Simona Gurzu
SOX11, SOX10 and MITF Gene Interaction: A Possible Diagnostic Tool in Malignant Melanoma
Life
melanoma cocktail
immunohistochemistry
SOX11
SOX10
MITF
survival
title SOX11, SOX10 and MITF Gene Interaction: A Possible Diagnostic Tool in Malignant Melanoma
title_full SOX11, SOX10 and MITF Gene Interaction: A Possible Diagnostic Tool in Malignant Melanoma
title_fullStr SOX11, SOX10 and MITF Gene Interaction: A Possible Diagnostic Tool in Malignant Melanoma
title_full_unstemmed SOX11, SOX10 and MITF Gene Interaction: A Possible Diagnostic Tool in Malignant Melanoma
title_short SOX11, SOX10 and MITF Gene Interaction: A Possible Diagnostic Tool in Malignant Melanoma
title_sort sox11 sox10 and mitf gene interaction a possible diagnostic tool in malignant melanoma
topic melanoma cocktail
immunohistochemistry
SOX11
SOX10
MITF
survival
url https://www.mdpi.com/2075-1729/11/4/281
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