title: SOX10 expression in superficial spreading and nodular malignant melanomas.
abstract: 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.
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Sweden. margret.agnarsdottir@genpat.uu.se
authors.forename: Margrét
authors.initials: M
authors.lastname: Agnarsdóttir
authors.forename: Linda
authors.initials: L
authors.lastname: Sooman
authors.forename: Asa
authors.initials: A
authors.lastname: Bolander
authors.forename: Sara
authors.initials: S
authors.lastname: Strömberg
authors.forename: Elton
authors.initials: E
authors.lastname: Rexhepaj
authors.forename: Michael
authors.initials: M
authors.lastname: Bergqvist
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ponten
authors.forename: William
authors.initials: W
authors.lastname: Gallagher
authors.forename: Johan
authors.initials: J
authors.lastname: Lennartsson
authors.forename: Simon
authors.initials: S
authors.lastname: Ekman
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlen
authors.forename: Håkan
authors.initials: H
authors.lastname: Hedstrand
mesh_terms: D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D055757:SOXE Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors