title: 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.
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.
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.|Department of Pathology, Mills Peninsula Medical Group, South San Francisco, CA, USA.
authors.forename: Thuy B
authors.initials: TB
authors.lastname: Nguyen
authors.affiliation: Department of Pathology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.|Department of Medical Biotechnology and Translational Medicine (BIOMETRA), University of Milan, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Roncalli
authors.affiliation: Department of Pathology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.|Department of Medical Biotechnology and Translational Medicine (BIOMETRA), University of Milan, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Di Tommaso
authors.affiliation: Department of Pathology, Mills Peninsula Medical Group, South San Francisco, CA, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kakar
mesh_terms: D018248:Adenoma, Liver Cell / Q000175:diagnosis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000032:analysis* / Q000096:biosynthesis; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis* / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018840:HSP70 Heat-Shock Proteins; D005974:Glutamate-Ammonia Ligase