Histogenesis of primary liver carcinomas: Strengths and weaknesses of cytokeratin profile and albumin mRNA detection

To assess the utility of cytokeratin (CK) profile and albumin mRNA detection (as revealed by in situ hybridization) in the differential diagnosis of primary liver carcinomas (PLCs) we evaluated a series of surgically resected PLCs, comprising 20 'pure' hepatocellular carcinomas (HCCs) (10 well-differentiated, 10 poorly differentiated), 15 cholangiocarcinomas (CCs) (6 peripheral, 5 hilar, and 4 major duct ones) and 10 hepatocholangio-carcinomas (HCC-CCs). 11 of 20 (55%) of the pure HCCs expressed CKs of pure hepatocytic lineage (CK 8 and CK 18); 2 of 10 (20%) of the HCC-CCs displayed only hepatocytic profile, whereas 12 of 15 (80%) of the CCs evidenced mature bile duct cell phenotype (CK 8, CK 18, CK 7, CK 19). All HCCs expressed varying distributions of albumin mRNA, whereas 4 of 6 (67%) peripheral CCs showed cells with focal positivity for albumin mRNA. This suggests that the phenotypic expression of PLC cells are often not fixed, and in particular: (1) peripheral CCs have a different phenotype from hilar and large duct ones; (2) the CK profile and albumin mRNA expression in peripheral CCs show many similarities with those of some HCCs. Furthermore, the results show that a mixed biological phenotype (ie, CK 8, CK 18 and CK 7 and/or CK 19) can be found both among morphologically pure HCCs and peripheral CCs, suggesting that these two forms could share a common histogenesis. We think that special attention should be given to cases in which CK profile and albumin mRNA reveal mixed phenotype, as these tumors could have different biological behavior and respond differently to therapy.