Immunohistochemical detection of EGFR, fibrillin-2, P-cadherin and AP2β as biomarkers for rhabdomyosarcoma diagnostics

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Abstract

Aims:

Subclassification of rhabdomyosarcoma (RMS) has clinical relevance, as the two major subclasses embryonal (ERMS) and alveolar (ARMS) rhabdomyosarcoma differ greatly in terms of aggressiveness and prognosis. However, histological analysis is not always sufficient for an unequivocal subclassification of RMS. Furthermore, clinical presentation of ARMS has been reported to mimic other tumour types, specifically lymphoma. The aim was to determine the role of four biomarkers in the diagnosis of rhabdomyosarcoma.

Methods and results:

Recently, we identified four potential biomarkers to subclassify RMS with high sensitivity and specificity. These included epidermal growth factor receptor (EGFR) and fibrillin-2 as markers for ERMS, and AP2β and P-cadherin as markers for translocation-positive ARMS. Here, we further validate the potential of these four markers in a second, independent patient cohort by immunohistochemistry on 80 sections of RMS biopsy specimens as well as a tissue microarray representing 18 different additional tumour types, including seven lymphomas. The combination of EGFR and fibrillin-2 was able to detect ERMS with a specificity of 76% and sensitivity of 90%. The combination of AP2β and P-cadherin detected ARMS with a specificity of 97% and sensitivity of 90%, data very similar to our previous study. Furthermore, all lymphomas were clearly negative for AP2β and P-cadherin.

Conclusions:

These four biomarkers are suitable for clinical implementation in the future diagnosis of RMS.

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