INTEGRINS AS DIFFERENTIAL CELL LINEAGE MARKERS OF PRIMARY LIVER-TUMORS

This study analyzed new cell lineage markers for the differential diag nosis between hepatocellular carcinoma (HCC) and cholangiocarcinoma (C hC), as well as the potential pathways of cell-cell and cell-extracell ular matrix interactions of neoplastic liver cells during tumor spread and invasion, by comparing the expression of (VLA) integrins, vitrone ctin receptor, and neural cell adhesion molecule in normal, inflamed, and neoplastic human liver biopsies. All cases of liver cell adenoma a nd well-differentiated HCC expressed the same set of integrins as obse rved in normal liver tissue, i.e., VLA-alpha1 and VLA-beta1. Poorly di fferentiated HCC also expressed VLA-alpha1 and VLA-beta1, but in addit ion de-novo expressed VLA-alpha2, VLA-alpha3, VLA-alpha6 and vitronect in receptor. All cases of well-differentiated CbC expressed an identic al integrin immunoprofile as observed in normal bile duct epithelium, i.e., VLA-alpha2, VLA-alpha3, VLA-alpha6, VLA-beta4 and vitronectin re ceptor, whereas poorly differentiated CbC showed a markedly decreased expression of these integrin subunits. VLA-alpha1 was constantly absen t from all cases of ChC, wbereas VLA-beta4 was never expressed by HCC Neural cell adhesion molecule, exclusively expressed by proliferating reactive bile ductules in cholestatic and regenerating liver, was cons tantly absent from both malignant neoplasms. In conclusion, the integr in make up of various liver tumors closely follows that of their norma l counterparts. Differences in integrin receptor expression vary ''cor ding to the cellular origin of the tumors and are associated with a po or differentiation. Our findings suggest that immunohistochemical stai ning for VLA-alpha1 and VLA-beta4 integrin subunits, which highlight t he cellular phenotype of the two neoplasms, might be a helpful tool in the differential diagnosis between HCC and ChC.