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Does PAX7 and NKX2.2 immunoreactivity in Ewing sarcoma have prognostic significance?

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Abstract

Ewing sarcoma (ES) is an aggressive neoplasm with variable morphology. It has no specific immunoprofile or molecular signature. Neither CD99, NKX2.2 nor PAX7 immunoreactivity alone is completely specific, although diagnostic specificity improves when combined. The purpose of the present study was to investigate the immunohistochemical (IHC) expression of PAX7 in a large series of genetically confirmed ES. Existing results for CD99 and NKX2.2 immunoexpression, morphological findings and molecular studies (fusion gene subtypes) were retrieved from a previous study. Survival analyses were performed in cases with available clinical follow-up. PAX7 was positive in 95.5% of ES with diffuse staining (> 50%) in all positive cases and moderate or strong intensity for most cases. Nineteen ES displayed both PAX7 and CD99 immunoreactivity but lacked NKX2.2 immunoexpression. No relationships could be found between PAX7 expression and the histological types or ES gene fusion subtypes. Univariant/multivariate analysis showed that lack of PAX7 and/or NKX2.2 immunoexpression constitute independent poor prognostic factors for progression free survival (PFS) and overall survival (OS). In conclusion, IHC for CD99, NKX2.2, and PAX7 may be useful in daily practice for ES diagnosis, particularly in hospitals lacking facilities for molecular studies. In addition, the combination of strong CD99 membranous positivity and nuclear PAX7 and NKX2.2 immunoreactivity seems to be very reliable for ES diagnosis when supported by a corroborating histomorphologic and clinical picture. Although PAX7 is not entirely specific for ES, it seems to have a more extensive and strong nuclear immunoreactivity than NKX2.2 expression, even in tumors with decalcification artifact. Considering the prognostically significant data herein reported, we strongly recommend validation in prospective ES series that include localized and disseminated tumors.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Local Ethics Committees.

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Acknowledgements

This study was supported by prognostic and therapeutic targets in the Ewing’s family of tumors, contract 503036, and EuroBoNet, European network to promote research into uncommon cancers in adults and children, contract 018814. The authors thank David Harrison for the English review and editing of the manuscript.

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Authors and Affiliations

  1. Department of Pathology, Instituto Valenciano de Oncología, 46009, Valencia, Spain

    Isidro Machado

  2. Patologika Laboratory, Hospital QuirónSalud, Valencia, Spain

    Isidro Machado

  3. Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA

    Gregory W. Charville

  4. Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan

    Akihiko Yoshida

  5. Department of Pathology, University of Valencia, Valencia, Spain

    Samuel Navarro & Antonio Llombart-Bosch

  6. Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy

    Alberto Righi & Marco Gambarotti

  7. Experimental Oncology Lab, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy

    Katia Scotlandi

  8. Department of Molecular Biology, Instituto Valenciano de Oncología, Valencia, Spain

    José A. López-Guerrero

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  1. Isidro Machado
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  2. Gregory W. Charville
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Contributions

Conceptualization: IM and AL-B; methodology: IM and JALG; formal analysis and investigation: IM, GWC, JALG, and AL-B; writing — original draft preparation: IM; writing — review and editing: IM, GWC, SN, AY, KS, MG, and AR; and supervision: AL-B.

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Correspondence to Isidro Machado.

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Machado, I., Charville, G.W., Yoshida, A. et al. Does PAX7 and NKX2.2 immunoreactivity in Ewing sarcoma have prognostic significance?. Virchows Arch 480, 909–917 (2022). https://doi.org/10.1007/s00428-021-03254-8

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