Research Articles

The Diagnostic Utility of IDH2 R172 Immunohistochemistry in Tall Cell Carcinoma With Reversed Polarity of the Breast

Sasaki, Eiichi MD, PhD^*,?; Iwakoshi, Akari MD, PhD^?,?; Satake, Tatsunari MD^§; Nakajima, Kosei MD, PhD^∥; Kobayashi, Mizuho MD, PhD^?; Ando, Yoshiaki MD, PhD^#; Koshikawa, Takashi MD, PhD^*,**; Masago, Katsuhiro MD, PhD^*; Honma, Naoko MD, PhD^??; Nishimura, Rieko MD, PhD^?; Kato, Yukinari MD, PhD^??,§§; Ichihara, Shu MD, PhD^?

Author Information

^*Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital

^?Clinical Research Center

^?Department of Pathology, National Hospital Organization Nagoya Medical Center

^§Department of Pathology, Nagoya Ekisaikai Hospital

^?Department of Pathology, Nagoya City University West Medical Center

^#Ando Breast Clinic, Nagoya

^∥Department of Surgical Pathology, Ichinomiya Municipal Hospital

^**Department of Medical Technology, Shubun University Faculty of Medical Sciences, Ichinomiya

^??Department of Pathology, Toho University Faculty of Medicine, Tokyo

^??Departments of Antibody Drug Development

^§§Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan

Supported by Nagoya Medical Center and by the Aichi Cancer Research Foundation.

E.S. and S.I. conceived and designed the study. E.S., A.I., T.S., K.N., M.K., Y.A., T.K., R.N., and S.I. contributed to the materials and patients. E.S., R.N., and S.I. provided a pathology review. E.S., K.M., and S.I. analyzed and interpreted the data. E.S. and S.I. wrote the paper. E.S. generated tables and figures. K.M., N.H., R.N., and Y.K. reviewed and edited the paper.

The authors declare no conflict of interest.

Reprints: Eiichi Sasaki, MD, PhD, Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan (e-mail: [email protected]).

Applied Immunohistochemistry & Molecular Morphology 30(10):p 654-661, November/December 2022. | DOI: 10.1097/PAI.0000000000001074

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Abstract

Tall cell carcinoma with reversed polarity (TCCRP) is a rare histologic type of low-grade breast cancer, consisting of tall columnar cells with reversed nuclear polarity and characterized by frequent IDH2 mutations. We herein report 3 cases of TCCRP with sequencing analyses of the IDH2 gene and immunohistochemical examination using monoclonal antibodies (11C8B1) against IDH2 R172. IDH2 R172 mutations were detected in all 3 resected tumors (R172S in 2 tumors and R172T in 1 tumor), and the presence of these mutations was confirmed by IDH2 R172 immunohistochemistry. Tumor cells of TCCRP showed strong and diffuse staining for the antibody against IDH2 R172. In 1 case, tumor tissue from 2 core needle biopsy samples collected on different days were also immunohistochemically positive for IDH2 R172. These results indicate that IDH2 R172 immunohistochemistry is suitable for the detection of TCCRP in both resection and biopsy samples. In addition, a literature review revealed that R172S and R172T account for 76% of IDH2 mutations in TCCRP, suggesting that 11C8B1, which reacts with R172S and R172T, was likely most sensitive for IDH2-mutated TCCRP among many available antibodies for IDH2 R172. Furthermore, the combination of 2 or more antibodies against IDH2 R172 could be more effective for detecting TCCRP mutation. However, it is important to note that IDH2 R172 immunohistochemistry is not absolute, because IDH2 wild type is found in a small proportion (10%) of cases, and a few cases of IDH2-mutated TCCRP may harbor rare subtypes of R172 that are not covered by available antibodies.