Expression of Intestinal Trefoil Factor (TFF-3) in Hepatocellular Carcinoma

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Trefoil peptides (TFF-1, 2, 3) are a family of protease-resistant regulatory factors that play a role in mucosal restitution, angiogenesis, apoptosis, and tumor progression. Intestinal trefoil peptide (TFF-3) expression has been demonstrated in benign hepatobiliary diseases, but there are limited data regarding its expression in HCC. Thirty consecutive cases of HCC from 1998 to 2003 were studied. Immunohistochemistry was performed on formalin-fixed paraffin-embedded blocks of HCC using polyclonal antibody to TFF-3. TFF-3 expression was classified as strong, moderate, weak, focal, and negative. Clinical data were obtained per an IRB-approved protocol. Median age was 69 yr (range: 39-83 yr). Twenty- three patients were males and 7 were females. Treatments included hepatic resection (n = 16), chemo-embolization (n = 4), combined modality therapy (n = 5) and no treatment (n = 4). HCC was well differentiated in 12 (40%), moderately differentiated in 13 (43%), and poorly differentiated in 5 (17%) patients. TFF-3 expression was detected in 28/30 (93.3%) patient samples. Sixteen patients (53%) had moderate and 1 (3%) patient had strong TFF-3 expression. Tumor/ normal tissue interface was assessable in 21 cases; 11 cases expressed TFF-3 at the interface. There was a strong correlation between tumor grade and TFF-3 expression, wherein poorly differentiated tumors had moderate/strong TFF-3 expression (p = 0.008). There was no correlation between TFF-3 expression and survival (p = 0.77). Furthermore, there was no correlation among age, disease stage, and survival. TFF-3 is commonly expressed in HCC and its expression correlates with tumor grade.