SOX10

by Jan Klos

Background

The SOX family of transcription factors (encoded by on chromosome 22q13.1) is involved in the regulation of embryonic development and the determination of cell fate.  SOX10 is a transport protein between nucleus and a cytoplasm and acting as a transcriptional activator.  It is important for development of neural crest and peripheral nervous system especially Schwann cells and melanocytes. SOX10 is also involved in the generation of myelin. There is evidence that SOX10 gene expression may be regulated by Microphtalmia Transcription Factor (MITF). Mutations in SOX10 are associated with Waardenburg syndrome and uveal melanoma. Some mutations may contribute to Hischprung`s disease. Despite a wide overlap in expression with S100 protein, there are important differences in reactivity with different tissues (eg. S100 stains positive chondroid tumors, chordoma, varying percentage of lipomatous tumors and a subset of adenocarcinomas where SOX10 is usually negative), which can be used in differential diagnosis of tumors.

Expression in normal cells

Nuclei of glial cells, Schwann cells, melanocytes and myoepithelial cells.

Expression in tumors

Many different tumors showing differentiation in above directions are positive, however percentage of positive cases is varying. Virtually all cases of melanocytic nevi and malignant melanoma (including desmoplastic and spindle cell melanomas, however the reactivity may be focal), schwannoma, neurofibroma, granular cell tumor, clear cell sarcoma of tendons and aponeuroses are positive. Majority of cases of salivary gland tumors (acinic cell carcinoma, adenoid cystic carcinoma, myoepithelioma, epithelial-myoepithelial and myoepithelial carcinoma, pleomorphic adenoma, canalicular adenoma) as well as oligodendroglioma, astrocytoma and glioblastoma are reported positive. About half of cases of basal-like and metaplastic triple-negative breast carcinomas but only rare cases of luminal type breast ductal carcinoma are positive. Minority of malignant nerve sheath tumor, some cases of adenocarcinoma of salivary glands and synovial sarcoma show positive staining. Negative are all other epithelial and mesenchymal tumors. Tumors like neuroblastoma, paraganglioma/pheochromocytoma and epithelial neuroendocrine tumors show positive staining only in sustentacular cells.

Staining pattern

Nuclear.

Control tissue

Skin and appendix.

Application

  • Detection of melanocytic, schwannian and myoepithelial neoplasms where SOX10 is more specific and probably more sensitive than S100 protein
  • Detection of metastatic melanoma in lymph nodes
  • Differential diagnosis of triple negative breast carcinoma in metastatic setting

Selected references

  1. Hsieh MS, Lee YH, Chang YL. SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma. Hum Pathol. 2016 Oct;56:134-42. doi: 10.1016/j.humpath.2016.05.021. Epub 2016 Jun 17.PMID: 27327192
  2. https://www.nordiqc.org/epitope.php?id=94
  3. Laurent E, Begueret H, Bonhomme B, et al. SOX10, GATA3, GCDFP15, Androgen Receptor, and Mammaglobin for the Differential Diagnosis Between Triple-negative Breast Cancer and TTF1-negative Lung Adenocarcinoma. Am J Surg Pathol. 2019 Mar;43(3):293-302. doi: 10.1097/PAS.0000000000001216.PMID: 30628926
  4. Miettinen M, McCue PA, Sarlomo-Rikala M, et al. SOX10-a marker for not only schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue: a systematic analysis of 5134 tumors.  Am J Surg Pathol. 2015 Jun;39(6):826-35. doi: 10.1097/PAS.0000000000000398.PMID: 25724000
  5. Tacha D, Qi W, Ra S, et al. A newly developed mouse monoclonal SOX10 antibody is a highly sensitive and specific marker for malignant melanoma, including spindle cell and desmoplastic melanomas. Arch Pathol Lab Med. 2015 Apr;139(4):530-6. doi: 10.5858/arpa.2014-0077-OA. Epub 2014 Dec 1.PMID: 25436903
  6. Tozbikian GH, Zynger DL. A combination of GATA3 and SOX10 is useful for the diagnosis of metastatic triple-negative breast cancer. Hum Pathol. 2019 Mar;85:221-227. doi: 10.1016/j.humpath.2018.11.005. Epub 2018 Nov 20.PMID: 30468800  
  7. Rooper LM, McCuiston AM, Westra WH, et al. SOX10 Immunoexpression in Basaloid Squamous Cell Carcinomas: A Diagnostic Pitfall for Ruling out Salivary Differentiation. Head Neck Pathol. 2019 Dec;13(4):543-547. doi: 10.1007/s12105-018-0990-7. Epub 2018 Nov 29.PMID: 30498968
  8. Willis BC, Johnson G, Wang J, et al. SOX10: a useful marker for identifying metastatic melanoma in sentinel lymph nodes. Appl Immunohistochem Mol Morphol. 2015 Feb;23(2):109-12. doi: 10.1097/PAI.0000000000000097.PMID: 25356946