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The Diagnostic Dilemma of GATA3 Immunohistochemistry in Pheochromocytoma and Paraganglioma

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Abstract

Although GATA3 has been recognized as a useful marker for mammary and urothelial carcinomas, there is large variation in GATA3 expression detected in pheochromocytoma (PC) and paraganglioma (PGL), from 90% to less than 5%. For GATA3 to be a useful diagnostic marker for PCCs/PGLs, the reasons for such discrepancy must be elucidated. Thus, we compared different immunohistochemistry protocols. Three protocols for GATA3 immunohistochemistry, including the use of an automated slide stainer or manual staining with an autoclave and EDTA buffer vs citric acid buffer, were compared. Whole sections of paraffin-embedded tumors, including 30 PCCs, 37 PGLs including 15 head and neck PGLs, 5 retroperitoneal PGLs, 17 urinary bladder PGLs, and 14 neuroblastoma group tumors, were examined and compared with mammary and urothelial carcinoma sections as positive controls. Using the automated slide stainer (Benchmark ULTRA; Ventana Medical Systems) with both buffers, mammary and urothelial carcinomas demonstrated strong GATA3 positivity; however, PCCs/PGLs showed negative or weak heterogeneous staining. Manual staining with an autoclave for antigen retrieval resulted in increased GATA3 immunoreactivity in all head and neck PGLs, all retroperitoneal PGLs, 88% of urinary PGLs, 17% of PCCs, and all neuroblastomas, except for ganglion cells. The normal adrenal medulla stained weakly and heterogeneously. In conclusions, immunohistochemistry for GATA3 in PCCs/PGLs requires stronger antigen retrieval than that in mammary and urinary carcinomas. This finding is especially important to consider if GATA3 is applied for the differential diagnosis of PGLs in unusual sites as supplemental data to the expression of catecholamine-synthesizing enzymes.

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Acknowledgments

The authors thank Okuyama D, M.T. and Azuma M, M.T. for their dedication and cooperation regarding the immunohistochemical work.

Funding

This study was conducted as a part of the JRAS by a Research Grant from the Japan Agency for Medical Research and Development (AMED) under Grant Number JP19ek010935.

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Authors and Affiliations

  1. Department of Diagnostic Pathology, National Hospital Organization Hakodate National Hospital, 18-16 Kawahara, Hakodate, Hokkaido, 041-8512, Japan

    Noriko Kimura

  2. Department of Head & Neck Surgery, Iwate Medical University Faculty of Graduate School of Medicine, Morioka, Iwate, Japan

    Kiyoto Shiga

  3. Department of Otolaryngology-Head and Neck Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Kenichi Kaneko

  4. Department of Diabetes, Metabolism, and Endocrinology, Showa University Fujigaoka Hospital, Yokohama, Kanagawa, Japan

    Chiho Sugisawa

  5. Department of Internal Medicine, Division of Metabolism and Endocrinology, St. Marianna University School of Medicine Yokohama City Seibu Hospital, Yokohama, Japan

    Takayuki Katabami

  6. Department of Endocrinology, Metabolism, and Hypertension, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan

    Mitsuhide Naruse

  7. Endocrine Center, Ijinkai Takeda General Hospital, Kyoto, Japan

    Mitsuhide Naruse

Authors
  1. Noriko Kimura
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  2. Kiyoto Shiga
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  3. Kenichi Kaneko
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  4. Chiho Sugisawa
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  5. Takayuki Katabami
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  6. Mitsuhide Naruse
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Noriko Kimura, Kiyoto Shiga, Kenichi Kaneko, Chiho Sugisawa, Takayuki Katabami, and Mitsuhide Naruse. The first draft of the manuscript was written by Noriko Kimura and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Noriko Kimura.

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Kimura, N., Shiga, K., Kaneko, K. et al. The Diagnostic Dilemma of GATA3 Immunohistochemistry in Pheochromocytoma and Paraganglioma. Endocr Pathol 31, 95–100 (2020). https://doi.org/10.1007/s12022-020-09618-1

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  • DOI: https://doi.org/10.1007/s12022-020-09618-1

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