Anna Szumera-Ciećkiewicz1, Francesca Bosisio2, Paweł Teterycz3, Asier Antoranz2, Francesco Delogu4, Senada Koljenović5, Bart A van de Wiel6, Willeke Blokx7, Léon C van Kempen8, Piotr Rutkowski3, Alexander Christopher van Akkooi9, Martin Cook10, Daniela Massi11. 1. Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Department of Diagnostic Hematology, Institute of Hematology and Transfusion Medicine Warsaw, Poland. Electronic address: szumann@gmail.com. 2. Laboratory of Translational Cell and Tissue Research and Pathology Department, KU Leuven and UZ Leuven, Leuven, Belgium. 3. Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland. 4. Department of Health Sciences, Clinical Pharmacology and Oncology Unit, University of Florence, Florence, Italy. 5. Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, the Netherlands. 6. Department of Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands. 7. Department of Pathology, Division of Laboratories, Pharmacy and Biomedical Genetics, University Medical Center, Utrecht, the Netherlands. 8. Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. 9. Department of Surgical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands. 10. Histopathology, Royal Surrey County Hospital, Guildford, UK. 11. Section of Pathological Anatomy, Department of Health Sciences, University of Florence, Florence, Italy.
Abstract
BACKGROUND: Sentinel lymph node (SLN) biopsy remains crucial for melanoma staging. The European Organisation for Research and Treatment of Cancer Melanoma Group recommends performing immunohistochemical stainings for reproducible identification of melanoma metastases. S100 protein (pS100) is a commonly used melanocytic antigen because of its high sensitivity in spite of relatively low specificity. SRY-related HMG-box 10 protein (SOX10) is a transcription factor characterising neural crest-derived cells. It is uniformly expressed mostly in the nuclei of melanocytes, neural, and myoepithelial cells. Pathologists sometimes prefer SOX10 as a melanoma marker, but it has not yet been investigated on a large-scale to confirm that it is reliable and recommendable for routine SLN evaluation. METHODS: Four hundred one treatment-naïve lymph node (LN) metastatic melanomas were included in high-density tissue microarrays and were assessed for the presence of SOX10 and pS100 by immunohistochemistry. The slides were digitalised, shared and evaluated by a panel of experienced melanoma pathologists. RESULTS: The vast majority of melanomas were double-positive for pS100 and SOX10 (93.2%); a small percentage of the cases (3.9%) were double-negative melanomas. Discordance between the two markers was observed: 1.9% pS100(-)/SOX10(+) and 0.75% pS100(+)/SOX10(-). SOX10 was not expressed by immune cell types in the LN, resulting in a less controversial interpretation of the staining. CONCLUSIONS: SOX10 is as equally specific as pS100 for the detection of melanoma metastases in LNs. The interpretation of SOX10 staining is highly reproducible among different centres and different pathologists because of the absence of staining of immune cells.
BACKGROUND: Sentinel lymph node (SLN) biopsy remains crucial for melanoma staging. The European Organisation for Research and Treatment of Cancer Melanoma Group recommends performing immunohistochemical stainings for reproducible identification of melanoma metastases. S100 protein (pS100) is a commonly used melanocytic antigen because of its high sensitivity in spite of relatively low specificity. SRY-related HMG-box 10 protein (SOX10) is a transcription factor characterising neural crest-derived cells. It is uniformly expressed mostly in the nuclei of melanocytes, neural, and myoepithelial cells. Pathologists sometimes prefer SOX10 as a melanoma marker, but it has not yet been investigated on a large-scale to confirm that it is reliable and recommendable for routine SLN evaluation. METHODS: Four hundred one treatment-naïve lymph node (LN) metastatic melanomas were included in high-density tissue microarrays and were assessed for the presence of SOX10 and pS100 by immunohistochemistry. The slides were digitalised, shared and evaluated by a panel of experienced melanoma pathologists. RESULTS: The vast majority of melanomas were double-positive for pS100 and SOX10 (93.2%); a small percentage of the cases (3.9%) were double-negative melanomas. Discordance between the two markers was observed: 1.9% pS100(-)/SOX10(+) and 0.75% pS100(+)/SOX10(-). SOX10 was not expressed by immune cell types in the LN, resulting in a less controversial interpretation of the staining. CONCLUSIONS:SOX10 is as equally specific as pS100 for the detection of melanoma metastases in LNs. The interpretation of SOX10 staining is highly reproducible among different centres and different pathologists because of the absence of staining of immune cells.