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SOX10 expression in superficial spreading and nodular malignant melanomas
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2010 (English)In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 20, no 6, 468-478 p.Article in journal (Refereed) Published
Abstract [en]

SOX10 is a transcription factor expressed in nerve cells and melanocytes. The aim of this study was to investigate the protein expression pattern of SOX10 in malignant melanoma tumors and to analyze whether the results correlated with clinical parameters and the proliferation marker Ki-67. Furthermore, proliferation and migration were analyzed in three different cell lines employing SOX10 small interfering RNA-mediated silencing. Expression patterns were determined in 106 primary tumors and 39 metastases in addition to 16 normal skin samples and six benign nevi employing immunohistochemistry and tissue microarrays. The immunohistochemical staining was evaluated manually and with an automated algorithm. SOX10 was strongly expressed in the benign tissues, but for the malignant tumors superficial spreading melanomas stained stronger than nodular malignant melanomas (P=0.008). The staining intensity was also inversely correlated with T-stage (Spearman's ρ=-0.261, P=0.008). Overall survival and time to recurrence were significantly correlated with SOX10 intensity, but not in multivariate analysis including T-stage. With the automated algorithm there was an inverse correlation between the SOX10 staining intensity and the proliferation marker, Ki-67 (ρ=-0.173, P=0.02) and a significant difference in the intensity signal between the benign tissues, the primary tumors and the metastases where the metastases stained the weakest (P≤0.001). SOX10 downregulation resulted in variable effects on proliferation and migration rates in the melanoma cell lines. In conclusion, the SOX10 intensity level differed depending on the tissue studied and SOX10 might have a role in survival. No conclusion regarding the role of SOX10 for in-vitro proliferation and migration could be drawn.

Place, publisher, year, edition, pages
2010. Vol. 20, no 6, 468-478 p.
Keyword [en]
Immunohistochemistry, malignant melanoma, small interfering RNA, SOX10
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-133423DOI: 10.1097/CMR.0b013e3283403ccdISI: 000283744100005PubMedID: 20890226OAI: oai:DiVA.org:uu-133423DiVA: diva2:369319
Available from: 2010-11-10 Created: 2010-11-10 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Biomarker Discovery in Cutaneous Malignant Melanoma: A Study Based on Tissue Microarrays and Immunohistochemistry
Open this publication in new window or tab >>Biomarker Discovery in Cutaneous Malignant Melanoma: A Study Based on Tissue Microarrays and Immunohistochemistry
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The incidence of cutaneous malignant melanoma has increased dramatically in Caucasians the last few decades, an increase that is partly explained by altered sun exposure habits. For the individual patient, with a localized disease, the tumor thickness of the excised lesion is the most important prognostic factor. However, there is a need to identify characteristics that can place patients in certain risk groups.

In this study, the protein expression of multiple proteins in malignant melanoma tumors was studied, with the aim of identifying potential new candidate biomarkers. Representative samples from melanoma tissues were assembled in a tissue microarray format and protein expression was detected using immunohistochemistry. Multiple cohorts were used and for a subset of proteins the expression was also analyzed in melanocytes in normal skin and in benign nevi. The immunohistochemical staining was evaluated manually and for part of the proteins also with an automated algorithm.

The protein expression of STX7 was described for the first time in tumors of the melanocytic lineage. Stronger expression of STX7 and SOX10 was seen in superficial spreading melanomas compared with nodular malignant melanomas. An inverse relationship between STX7 expression and T-stage was seen and between SOX10 expression and T-stage and Ki-67, respectively. In a population-based cohort the expression of MITF was analyzed and found to be associated with prognosis. Twenty-one potential biomarkers were analyzed using bioinformatics tools and a protein signature was identified which had a prognostic value independent of T-stage. The protein driving this signature was RBM3, a protein not previously described in malignant melanoma. Other markers included in the signature were MITF, SOX10 and Ki-67.

In conclusion, the protein expression of numerous potential biomarkers was extensively studied and a new prognostic protein panel was identified which can be of value for risk stratification.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 53 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 644
Keyword
antibody-based proteomics, automated analysis, biomarker, immunohistochemistry, malignant melanoma, survival, tissue microarray
National Category
Cell and Molecular Biology Cell and Molecular Biology Cell and Molecular Biology
Research subject
Medical Science; Pathology
Identifiers
urn:nbn:se:uu:diva-146436 (URN)978-91-554-8007-3 (ISBN)
Public defence
2011-04-02, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjöldsv 20, Uppsala, 13:15 (English)
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Supervisors
Available from: 2011-03-11 Created: 2011-02-16 Last updated: 2011-05-04Bibliographically approved

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