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.

Sox10 is expressed in primary melanocytic neoplasms of various histologies but not in fibrohistiocytic proliferations and histiocytoses

“…Nevi and primary melanomas showed diffuse nuclear positivity in every case with 90% to 100% of tumor nuclei staining strongly. Prior studies documented Sox10 positivity in primary invasive melanomas and metastatic melanomas, 9,12,13,32 but a comprehensive comparison of histologic subtypes had not previously been conducted. Since Sox10 is a nuclear stain, it provides the ease of interpretation of MITF, yet it has the added advantage that it does not stain cells of the fibrohistiocytic/histiocytic lineage, so it can be used to assess for superficial dermal invasion in primary melanomas, akin to Melan-A.…”

“…9,11,12 The primary melanomas that were studied were not analyzed by histologic subtype or only singular specific subtypes were analyzed. [9][10][11]13 Thus, a systematic study of primary melanocytic lesions has yet to be conducted. In addition, while some fibrohistiocytic proliferations have been shown to lack Sox10 expression, others such as atypical fibroxanthoma and neurothekeoma, as well as histiocytoses such as xanthogranuloma, and Langerhans cell histiocytosis, which are often in the morphologic differential diagnosis of primary melanocytic lesions, have yet to be analyzed.…”

SOXs in human prostate cancer: implication as progression and prognosis factors

“…SOX10 has been implicated in the late stage of neural crest cell formation, maintenance of multipotency crest cells as stem cells and specification of derivative cell fates to Schwannian and melanocytic destinations [24-26]. Mutations in the SOX10 gene have been reported in a fraction of both primary and metastatic melanoma tumors [27]. The immunohistochemistry analysis has also been employed to map the expression of SOX10 in various human tissues and SOX10 has been suggested to be a specific and sensitive marker for melanocytic tumors [28].…”

Enhanced SOX10 and KIT expression in cutaneous melanoma

“…SOX10 and KIT are also highly involved in the development of melanoma. Moreover, SOX10 has been shown to be a marker for melanocytic tumors and its protein expression can be correlated with benign nevi progression to superficial spreading melanoma but not nodular melanoma [1]. However, at present there are no studies investigating the mRNA level of SOX10 in melanoma progression.…”

“…Lars Rönnstrand 1 The transcription factor SOX10 and the receptor tyrosine kinase KIT are well recognized for their importance in melanocyte development. SOX10 and KIT are also highly involved in the development of melanoma.…”