Utility of SOX6 and DAB2 for the Diagnosis of Malignant Mesothelioma

Am J Surg Pathol. 2021 Sep 1;45(9):1245-1251. doi: 10.1097/PAS.0000000000001712.


The separation of malignant mesothelioma from non-small cell lung carcinomas can be a difficult problem. Sex-determining region Y box 6 (SOX6) and disabled homolog 2 (DAB2) have recently been proposed as sensitive/specific markers of mesothelial lineage, but have not yet been independently tested for utility in mesothelioma diagnosis. Using tissue microarrays containing mesotheliomas (epithelioid: n=40, sarcomatoid: n=23) and non-small cell lung carcinomas (adenocarcinoma: n=52, squamous cell carcinoma: n=57, large cell carcinoma: n=12) we evaluated the performance of SOX6 and DAB2 by themselves, in conjunction with other established mesothelioma markers (calretinin, WT1, D2-40, CK5/6, HEG1) and combined with 3 broad-spectrum established carcinoma markers: claudin-4, MOC31, and BerEP4. For epithelioid mesothelioma, SOX6 and DAB2 had sensitivities of 85% and 98%, respectively. For sarcomatoid mesothelioma, SOX6 had a sensitivity of 13% and DAB2 could not be assessed due to background stromal staining. For SOX6 alone, specificity for mesothelioma versus adenocarcinoma, squamous cell carcinoma, and large cell carcinoma was 94%, 79%, and 92%, respectively, while for DAB2 specificity was 77%, 86%, and 67%. Combinations of SOX6 and established mesothelioma markers produced sensitivities of 95% or greater. A combination of SOX6 positive/claudin-4 negative staining was 95% to 100% specific for mesothelioma versus carcinoma with a sensitivity of 85%. SOX6 is a promising marker for the diagnosis of mesothelioma and potentially could be combined with other mesothelial markers or a broad-spectrum carcinoma marker to reach an accurate diagnosis with relatively few immunostains, The relatively low specificity and difficulty of interpreting DAB2 staining limits its utility for mesothelioma diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis*
  • Apoptosis Regulatory Proteins / analysis*
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Diagnosis, Differential
  • Humans
  • Lung Neoplasms / diagnosis
  • Mesothelioma, Malignant / diagnosis*
  • SOXD Transcription Factors / analysis*
  • Sensitivity and Specificity


  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Biomarkers, Tumor
  • DAB2 protein, human
  • SOX6 protein, human
  • SOXD Transcription Factors