-Original-

Immunohistochemical Diagnosis of Amyloid Typing: Utility and Limitations as Determined by Liquid Chromatography-Tandem Mass Spectrometry

Yukako Shintani-Domoto¹, Kousuke Ishino², Takenori Fujii², Taeko Kitamura², Kiyoshi Teduka², Hironobu Naiki³, Takashi Sakatani¹ and Ryuji Ohashi^1,2

¹Department of Diagnostic Pathology, Nippon Medical School Hospital, Tokyo, Japan
²Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo, Japan
³Department of Molecular Pathology, University of Fukui, Fukui, Japan

Background: Although immunohistochemical techniques and proteomic analysis are widely used for typing diagnosis of amyloidosis, the diagnostic utility of immunohistochemical evaluation is not well understood.
Methods: We used immunohistochemical techniques to characterize staining patterns of in-house rabbit polyclonal anti-κ, anti-λ, anti-transthyretin antibodies, and commercial anti-amyloid A and anti-β₂-microglobulin antibodies in 40 autopsy cases.
Results: In thirty cases (75%), the subtype was determined by using the criterion that amyloid is strongly and diffusely positive for one antibody while negative for other antibodies. We then performed proteomic analysis of all 40 cases. In 39 cases, we identified only one amyloid protein and confirmed the immunohistochemically determined subtypes of the abovementioned 30 cases. In seven other cases, we could retrospectively determine subtypes with immunohistochemistry by using information from proteomic analysis, which increased the immunohistochemistry diagnosis rate to 92.5% (37/40). In one case, we identified double subtypes, both immunohistochemically and with proteomic analysis. In the remaining three cases, proteomic analysis was essential for typing diagnosis.
Conclusions: The present findings suggest that combined immunohistochemistry and proteomic analysis is more useful than immunohistochemistry alone. Our findings highlight the importance of carefully interpreting immunohistochemistry for anti-TTR and light chain and offer insights that can guide amyloid typing through immunohistochemistry.

J Nippon Med Sch 2024; 91: 261-269

Keywords
amyloidosis, immunohistochemistry, autopsy, mass spectrometry

Correspondence to
Yukako Shintani-Domoto, MD, PhD, Department of Diagnostic Pathology, Nippon Medical School Hospital, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
yukakoshintani@gmail.com

Received, August 2, 2023
Accepted, December 13, 2023