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Immunohistochemical stains of proliferating cell nuclear antigen, insulin-like growth factor 2 and clusterin help distinguish malignant from benign liver nodular lesions
  1. Jin-Ping Lai1,2,
  2. Zong-Ming E Chen3,
  3. Terry Lok1,
  4. Owen T M Chan4,
  5. Eric Himmelfarb5,
  6. Qihui Zhai6,
  7. Fan Lin3,
  8. Hanlin L Wang1
  1. 1Department of Pathology and Laboratory Medicine, University of California in Los Angeles, Los Angeles, California, USA
  2. 2Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, California, USA
  3. 3Department of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA
  4. 4Department of Pathology, University of Hawaii, Honolulu, Hawaii, USA
  5. 5PML Pathology, Asheville, North Carolina, USA
  6. 6Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA
  1. Correspondence to Professor Hanlin L Wang, Department of Pathology and Laboratory Medicine, University of California in Los Angeles, 10833 Le Conte Ave, 13-145 CHS, Los Angeles, CA 90095, USA; hanlinwang{at}


Aims 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.

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