title: A novel panel of biomarkers in distinction of small well-differentiated HCC from dysplastic nodules and outcome values.
abstract: BACKGROUND
  Differential diagnosis of high-grade dysplastic nodules (HGDN) and well-differentiated hepatocellular carcinoma (WDHCC) represents a challenge to experienced hepatic clinicians, radiologists and hepatopathologists.
  
  
  METHODS
  The expression profiles of aminoacylase-1 (ACY1), sequestosome-1 (SQSTM1) and glypican-3 (GPC3) in low-grade dysplastic nodules (LGDN), HGDN and WDHCC were assessed by immunohistochemistry. The differential diagnostic performances of these three markers alone and in combination for HGDN and WDHCC were investigated by logistic regression models (HGDN = 21; WDHCC = 32) and validated in an independent test set (HGDN, n = 21; WDHCC n = 24). Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses in an independent set of 500 patients.
  
  
  RESULTS
  ACY1, SQSTM1 and GPC3 were differentially expressed in each group. For the differential diagnosis of WDHCC from HGDN, the sensitivity and specificity of the combination of ACY1 + SQSTM1 + GPC3 for detecting WDHCC were 93.8% and 95.2% respectively in the training set, which were higher than any of the three two-marker combinations. The validities of the four diagnostic models were further confirmed in an independent test set, and corresponding good sensitivity and specificity were observed. Interestingly, GPC3 expression in HCC tissues combined with serum α-fetoprotein (AFP) was found to be an independent predictor for overall survival and time to recurrence.
  
  
  CONCLUSIONS
  ACY1 + SQSTM1 + GPC3 combination represents a potentially valuable biomarker for distinguishing between WDHCC and HGDN using immunohistochemistry. Meanwhile, low GPC3 staining combined with positive serum AFP may play a practical role in predicting poor postoperative outcome and high tumor recurrence risk.
authors.affiliation: Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Guang-Zhi
authors.initials: GZ
authors.lastname: Jin
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Lu
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Xian
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.forename: Yin-Kun
authors.initials: YK
authors.lastname: Liu
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Cong
authors.forename: Meng-Chao
authors.initials: MC
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000581:Amidohydrolases / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D003937:Diagnosis, Differential; D053673:Glypicans / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D060787:Neoplasm Grading; D011379:Prognosis; D012372:ROC Curve; D015203:Reproducibility of Results; D012189:Retrospective Studies; D000071456:Sequestosome-1 Protein; D046888:Tissue Array Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C105937:GPC3 protein, human; D053673:Glypicans; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D000581:Amidohydrolases; C019672:aminoacylase I
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