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Large-Scale Tissue Microarray Evaluation Corroborates High Specificity of High-Level Arginase-1 Immunostaining for
Maximilian Lennartz1, Eva Gehrig1, Sören Weidemann1
1Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Diagnostics (Basel, Switzerland)
|December 24, 2021
Summary
Arginase-1 is a sensitive marker for hepatocellular carcinoma, especially when excluding weak or focal staining. This study comprehensively analyzed arginase-1 expression across numerous normal and tumor tissues.
Area of Science:
- Biochemistry
- Oncology
- Immunohistochemistry
Background:
- Arginase-1 (ARG1) catalyzes arginine breakdown, producing ornithine and urea.
- ARG1 is predominantly expressed in hepatocytes, making it a potential biomarker for hepatocellular carcinoma (HCC).
- However, ARG1 expression can occur in other tumor types, necessitating a comprehensive analysis.
Purpose of the Study:
- To investigate the expression patterns of arginase-1 in a wide range of normal and neoplastic human tissues.
- To determine the diagnostic utility of arginase-1 immunohistochemistry for hepatocellular carcinoma.
- To identify other tumor types that may express arginase-1.
Main Methods:
- Utilized immunohistochemistry to analyze arginase-1 expression.
- Examined 14,912 tissue microarray samples from 117 tumor types and 608 samples from 76 normal tissue types.
- Correlated arginase-1 expression with clinicopathological features, such as tumor grade.
Main Results:
- Normal tissues showed arginase-1 expression in the liver, epidermis (granular layer), and granulocytes.
- Hepatocellular carcinoma exhibited predominantly nuclear and cytoplasmic arginase-1 staining in 96% of cases.
- Occasional arginase-1 immunostaining was noted in 22 other tumor categories, particularly in squamous differentiation areas of squamous cell carcinomas, teratomas, urothelial carcinomas, and pleomorphic adenomas. Staining in squamous cell carcinomas was associated with lower tumor grade.
Conclusions:
- Arginase-1 immunohistochemistry is a highly sensitive and specific marker for hepatocellular carcinoma when weak and focal staining are disregarded.
- Occasional arginase-1 expression in other tumors, especially those with squamous differentiation, should be considered in differential diagnosis.
- This comprehensive analysis provides valuable insights into arginase-1 expression across human tissues, aiding in cancer diagnosis and research.

