Aberrant dipeptidyl peptidase IV (DPP IV/CD26) expression in human hepatocellular carcinoma

Diagnosis of small nodular lesions in the liver is often difficult because polarization of hepatocytes under pathological conditions is not as easily determined as for glandular or squamous epithelia. The aim of the present study was to investigate whether the bile canalicular enzyme dipeptidyl peptidase IV (DPP IV) would be useful to assess the pattern of hepatocellular surface polarity in liver sections.

Expression of DPP IV activity was determined by enzymatic cytochemistry and image cytometry in 25 human hepatocellular carcinomas and five cirrhotic livers removed at transplantation. Samples from the central and/or peripheral portion of neoplastic nodules and from surrounding tissue were analyzed in each case. Control specimens were obtained from normal liver of seven patients who underwent surgery for non-neoplastic conditions.

In normal liver, DPP IV activity was confined to the bile canalicular plasma membrane with a zone 3 predominance in the hepatic acinus. This was also the case in the majority of pathological non-neoplastic livers, but the cell distribution pattern of DPP IV was altered in all hepatocellular carcinomas: 2/25 cases were completely devoid of DPP IV activity and in the remaining 23 DPP IV expressing hepatocellular carcinomas, three different patterns were observed that deviated distinctly from the typical canalicular pattern: (i) canaliculi were distorted and convoluted and contained an abnormally high DPP IV activity; (ii) canalicular activity was lost and enzymatic activity was restricted to isolated spots; (iii) pseudoacinar structures of hepatocytes with both basolateral and apical DPP IV expression appeared.

It is concluded that DPP IV is a useful bile canalicular enzyme to assess the functional polarization of hepatocytes and that aberrant DPP IV expression occurs in human hepatocellular carcinoma.