ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2016
Combined use of heat-shock protein 70 and glutamine synthetase is useful in the distinction of typical hepatocellular adenoma from atypical hepatocellular neoplasms and well-differentiated hepatocellular carcinoma.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 54 citations in OpenAlex.
- Giant Atypical Hepatocellular Adenoma of Unknown Etiology in a Young Male: A Case Report.Journal of hepatocellular carcinoma · 2026Article
- Neoadjuvant therapy for hepatocellular carcinoma: emerging combinations and biomarker challenges.Frontiers in immunology · 2026Review
- Glutaminase Reprogramming in Hepatocellular Carcinoma: Implications for Diagnosis, Prognosis, and Potential as a Novel Therapeutic Target.International journal of molecular sciences · 2025Article
- An Update of Immunohistochemistry in Hepatocellular Carcinoma.Diagnostics (Basel, Switzerland) · 2025Review
- A Case Presentation of Well-Differentiated Hepatocellular Carcinoma With No Sign of Liver Disease.Cureus · 2024Article
- P53 and VEGF are promising biomarkers for sorafenib efficacy in an experimental model of NASH-related HCC.Journal of molecular histology · 2023Article
- Rare benign liver tumors that require differentiation from hepatocellular carcinoma: focus on diagnosis and treatment.Journal of cancer research and clinical oncology · 2023Article
- Adult hepatoblastoma: making the challenging distinction from hepatocellular carcinoma.Journal of liver cancer · 2023Article
- Therapeutic efficacy of atezolizumab plus bevacizumab for hepatocellular carcinoma with WNT/β-catenin signal activation.Oncology letters · 2022Article
- A case of focal nodular hyperplasia with hepatic failure treated with liver transplantation.Clinical journal of gastroenterology · 2022Article
- Application of Immunohistochemistry in the Pathological Diagnosis of Liver Tumors.International journal of molecular sciences · 2021Review
- Ki-67 "hot spot" digital analysis is useful in the distinction of hepatic adenomas and well-differentiated hepatocellular carcinomas.Virchows Archiv : an international journal of pathology · 2021Article
- Abnormal expression of HNRNPA3 in multistep hepatocarcinogenesis.Oncology letters · 2021Article
- Biopsies of hepatocellular carcinoma with no reticulin loss: an important diagnostic pitfall.Human pathology · 2021Article
- Malignant transformation of liver fatty acid binding protein-deficient hepatocellular adenomas: histopathologic spectrum of a rare phenomenon.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- Assessment of liver cancer biomarkers.Gastroenterology and hepatology from bed to bench · 2020Review
- Multi-parameter ultrasound based on the logistic regression model in the differential diagnosis of hepatocellular adenoma and focal nodular hyperplasia.World journal of gastrointestinal oncology · 2019Article
- Improving Anti-Cancer Potentiality and Bioavailability of Gallic Acid by Designing Polymeric Nanocomposite FormulationAsian Pacific journal of cancer prevention : APJCP · 2018Article
- Changing role of histopathology in the diagnosis and management of hepatocellular carcinoma.World journal of gastroenterology · 2018Review
- The loss of CD44 and HSP70 overexpression is related to aggressive clinicopathologic factors in prostate cancer.International journal of clinical and experimental pathology · 2018Article
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
Abstract
Well-differentiated hepatocellular carcinoma can mimic high-grade dysplastic nodule in cirrhotic liver and hepatocellular adenoma in non-cirrhotic liver. This study evaluates the efficacy of combined use of heat-shock protein 70 (HSP70), glutamine synthetase (GS) and glypican-3 in this setting. Immunohistochemistry for these three markers was done in 17 typical hepatocellular adenoma, 15 high-grade dysplastic nodules, 20 atypical hepatocellular neoplasms (14 clinically atypical and 6 pathologically atypical), 14 very well-differentiated hepatocellular carcinoma, and 43 well-differentiated hepatocellular carcinoma. All three markers were negative in typical adenomas. HSP70 was positive in 10, 71, and 67% of atypical neoplasms, very well-differentiated and well-differentiated HCC, respectively, while GS was positive in 60, 50, and 60% of atypical neoplasms, very well-differentiated and well-differentiated hepatocellular carcinoma, respectively. Glypican-3 was negative in all atypical neoplasms and very well-differentiated hepatocellular carcinoma, and was positive in 27% of well-differentiated hepatocellular carcinoma. Positive staining with at least one marker (HSP70 and/or GS) was seen in 85% of very well-differentiated hepatocellular carcinoma, which was similar to well-differentiated hepatocellular carcinoma (78%, P=0.4), and pathologically atypical cases (100%, P=0.5), but significantly higher compared with clinically atypical cases (43%. P=0.03) and none of typical adenomas (P<0.001). Positive staining with both GS and HSP70 was seen significantly more often in hepatocellular carcinoma compared with atypical neoplasms (45 vs 10%, P=0.004). Both these markers were also more often expressed in very well-differentiated hepatocellular carcinoma compared with atypical cases (38 vs 10%, P=0.06). In conclusion, the combined use of GS and HSP70 can be useful in the diagnosis of very well-differentiated hepatocellular carcinoma. These stains can also help in the distinction of typical adenoma from atypical hepatocellular neoplasms. Glypican-3 has low sensitivity and is not useful in this setting.
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