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Immunohistochemical NF1 Analysis Does not Predict NF1 Gene Mutation Status in Pheochromocytoma

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Abstract

Pheochromocytomas (PCCs) are tumors originating from the adrenal medulla displaying a diverse genetic background. While most PCCs are sporadic, about 40 % of the tumors have been associated with constitutional mutations in one of at least 14 known susceptibility genes. As 25 % of sporadic PCCs harbor somatic neurofibromin 1 gene (NF1) mutations, NF1 has been established as the most recurrently mutated gene in PCCs. To be able to pinpoint NF1-related pheochromocytoma (PCC) disease in clinical practice could facilitate the detection of familial cases, but the large size of the NF1 gene makes standard DNA sequencing methods cumbersome. The aim of this study was to examine whether mutations in the NF1 gene could be predicted by immunohistochemistry as a method to identify cases for further genetic characterization. Sixty-seven PCCs obtained from 67 unselected patients for which the somatic and constitutional mutational status of NF1 was known (49 NF1 wild type, 18 NF1 mutated) were investigated for NF1 protein immunoreactivity, and the results were correlated to clinical and genetic data. NF1 immunoreactivity was absent in the majority of the PCCs (44/67; 66 %), including 13 out of 18 cases (72 %) with a somatic or constitutional NF1 mutation. However, only a minority of the NF1 wild-type PCCs (18/49; 37 %) displayed retained NF1 immunoreactivity, thereby diminishing the specificity of the method. We conclude that NF1 immunohistochemistry alone is not a sufficient method to distinguish between NF1-mutated and non-mutated PCCs. In the clinical context, genetic screening therefore remains the most reliable tool to detect NF1-mutated PCCs.

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Acknowledgments

This work was supported by grants from the StratCan (Strategic Research Programme in Cancer at Karolinska Institutet), the Swedish Cancer Foundation, the Cancer Society in Stockholm, and through the regional agreement on medical training and clinical research (ALF) between the Stockholm County Council and Karolinska Institutet. The authors wish to thank Drs. Catharina Larsson and Anders Höög, Karolinska Institutet, Stockholm, Sweden for scientific communications, as well as Ms. Lisa Ånfalk, Karolinska University Hospital, Stockholm, Sweden for excellent tissue sample handling.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Oncology and Pathology, Karolinska Institutet, SE-17176, Stockholm, Sweden

    Adam Stenman, Fredrika Svahn & C. Christofer Juhlin

  2. Cancer Center Karolinska, CCK, Karolinska University Hospital Solna, SE-17176, Stockholm, Sweden

    Adam Stenman, Fredrika Svahn & C. Christofer Juhlin

  3. Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-58185, Linköping, Sweden

    Jenny Welander, Peter Söderkvist & Oliver Gimm

  4. Department of Clinical Pathology and Cytology, Radiumhemmet, Karolinska University Hospital Solna, SE-17176, Stockholm, Sweden

    Boel Gustavson & C. Christofer Juhlin

  5. Department of Surgery, County Council of Östergötland, SE-58185, Linköping, Sweden

    Oliver Gimm

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  1. Adam Stenman
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  2. Fredrika Svahn
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  3. Jenny Welander
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  5. Peter Söderkvist
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  7. C. Christofer Juhlin
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Corresponding author

Correspondence to C. Christofer Juhlin.

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Adam Stenman and Fredrika Svahn contributed equally to this work.

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Stenman, A., Svahn, F., Welander, J. et al. Immunohistochemical NF1 Analysis Does not Predict NF1 Gene Mutation Status in Pheochromocytoma. Endocr Pathol 26, 9–14 (2015). https://doi.org/10.1007/s12022-014-9348-1

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  • DOI: https://doi.org/10.1007/s12022-014-9348-1

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