title: Immunohistochemical stains of proliferating cell nuclear antigen, insulin-like growth factor 2 and clusterin help distinguish malignant from benign liver nodular lesions.
abstract: OBJECTIVE
  To explore the immunohistochemical utility of proliferating cell nuclear antigen (PCNA), insulin-like growth factor 2 (IGF2) and clusterin in the distinction between malignant and benign liver nodular lesions.
  
  
  METHODS
  Immunohistochemical stains for PCNA, IGF2 and clusterin were performed on 284 liver nodular lesions, including 33 hepatocellular adenomas (HCA), 40 focal nodular hyperplasias (FNH), 77 large regenerative nodules (LRN) and 134 hepatocellular carcinomas (HCC).
  
  
  RESULTS
  Strong and diffuse nuclear PCNA immunoreactivity was observed in 103 (77%) HCCs but in only 2 (6%) HCAs. None of the FNH and LRN cases showed a strong and diffuse staining pattern. All HCAs, 95% of FNHs and 92% of LRNs showed cytoplasmic IGF2 expression, with a strong staining observed in 70% of HCAs, 20% of FNHs and 30% of LRNs. This was in marked contrast to that observed in HCCs, where 66% of HCCs demonstrated a weak and focal/patchy immunostaining pattern and another 25% showed no detectable IGF2 immunoreactivity. In comparison with their adjacent non-lesional hepatocytes, 75% of HCCs showed decreased IGF2 expression. However, decreased IGF2 expression was not evident in HCAs, FNHs and LRNs. Cytoplasmic staining for clusterin was seen in both benign and malignant nodular lesions. However, an enhanced and exaggerated pericanalicular staining pattern was observed in 75% of HCCs, which was not demonstrated in HCAs, FNHs and LRNs.
  
  
  CONCLUSIONS
  PCNA, IGF2 and clusterin show unique immunostaining characteristics in HCCs, which can be useful adjuncts to other currently available markers to aid in the distinction of HCC from benign liver nodular lesions.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California in Los Angeles, Los Angeles, California, USA Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Lai
authors.affiliation: Department of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA.
authors.forename: Zong-Ming E
authors.initials: ZM
authors.lastname: Chen
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California in Los Angeles, Los Angeles, California, USA.
authors.forename: Terry
authors.initials: T
authors.lastname: Lok
authors.affiliation: Department of Pathology, University of Hawaii, Honolulu, Hawaii, USA.
authors.forename: Owen T M
authors.initials: OT
authors.lastname: Chan
authors.affiliation: PML Pathology, Asheville, North Carolina, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Himmelfarb
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA.
authors.forename: Qihui
authors.initials: Q
authors.lastname: Zhai
authors.affiliation: Department of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Lin
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California in Los Angeles, Los Angeles, California, USA.
authors.forename: Hanlin L
authors.initials: HL
authors.lastname: Wang
mesh_terms: D018248:Adenoma, Liver Cell / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D051152:Clusterin / Q000032:analysis*; D003937:Diagnosis, Differential; D020518:Focal Nodular Hyperplasia / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008099:Liver / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D008115:Liver Regeneration; D011237:Predictive Value of Tests; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; C495242:CLU protein, human; D051152:Clusterin; C035170:IGF2 protein, human; D018809:Proliferating Cell Nuclear Antigen; D007335:Insulin-Like Growth Factor II