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Cytoplasmic Staining of TTF-1 in the Differential Diagnosis of Hepatocellular Carcinoma vs Cholangiocarcinoma and Metastatic Carcinoma of the Liver

Jun-Yi Lei MD, PhD, Patricia A. Bourne, P. Anthony diSant’Agnese MD, Jiaoti Huang MD, PhD
DOI: http://dx.doi.org/10.1309/59TNEFALUL5WJ94M 519-525 First published online: 1 April 2006


The cytoplasmic staining of thyroid transcription factor (TTF)-1 was analyzed in 86 liver resection specimens, including 40 hepatocellular carcinoma (HCC), 4 metastatic HCC, 20 cholangiocarcinoma, 2 combined hepatocellular-cholangiocarcinoma (CHC), and 20 metastatic carcinoma (MC), with immuno-histochemical stains to TTF-1, cytokeratin (CK)19, hepatocyte paraffin 1, α-fetoprotein, polyclonal carcinoembryonic antigen, CK7, and CK20. TTF-1 cytoplasmic staining was identified in 93% of HCCs (37/40), 100% of metastatic HCCs (4/4), 10% of cholangiocarcinomas (2/20), and 5% of MCs (1/20). CK19 was positive in all cholangiocarcinomas and MCs but only in 5% of HCCs (2/40) and none of the metastatic HCCs (0/4). TTF-1 cytoplasmic staining positively correlates with differentiation and the trabecular growth pattern of HCC. The results suggest TTF-1 cytoplasmic staining, together with CK19, might serve as a useful marker for the diagnosis of primary and metastatic HCC and for the differential diagnosis of HCC from cholangiocarcinoma and MC. The mechanism of TTF-1 cytoplasmic staining is explored.

Key Words:
  • Thyroid transcription factor-1
  • TTF-1
  • Immunohistochemistry
  • Hepatocellular carcinoma
  • Cholangiocarcinoma