Electrophoretic behavior and partial characterization of disease‐associated serum forms of gammaglutamyltransferase

Abstract

We have recently devised an improved procedure for the rapid electrophoretic separation of multiple forms of serum gamma-glutamyltransferase (GGT). This procedure is based on the separation on cellulose acetate strips, usually employed for lipoprotein electrophoresis, followed by visualization with a fluorescent reagent. The method is highly sensitive and the fractions are more clearly resolved than with other procedures. Reference intervals have been evaluated in the sera from 142 healthy subjects and the patterns (two GGT forms comigrating with alpha 1 and alpha 2-globulin) are reproducible. In 150 sera from patients with various hepatobiliary diseases (including neoplasias), acute pancreatitis and non liver-involving neoplasias, we observed some disease-specific GGT forms: an albumin comigrating enzyme (Alb-GGT) specific of liver neoplasia; a gamma-globulin comigrating GGT (gamma-GGT) and a nonmigrating isoform (dep-GGT) both specifically associated to extrahepatic jaundice. Multiple lipoprotein fraction precipitation showed that beta-, gamma- and dep-GGT are complexes between GGT and low density lipoprotein and very low density lipoproteins (LDL + VLDL), and that some of the alpha 1-GGT from cirrhotic patients is a complex between GGT and high density lipoprotein (HDL). GGT fractions from normal subjects and Alb-GGT from patients with liver neoplasia do not appear to be complexed with lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the albumin‐γ‐glutamyltransferase isoenzyme as a diagnostic marker of hepatocellular carcinoma‐complicating liver cirrhosis

“…Considering the widespread distribution of GGT in normal tissues, it is not surprising that tumor-associated isoforms are encountered in patients with various forms of malignancy. 21,25,31 In fact, the MLD patients with serum alb-GGT had primary tumors of the pancreas (three cases), colon (two cases), stomach (one case), biliary system (one case) or of unknown origin (two cases). The presence of tumor-linked GGT isoenzymes in some cirrhotics without detectable HCC, already reported by other groups, 23,26 is less easily explained.…”

“…28 Both a1 and a2-GGT are usually found in normal subjects, 39 while b-GGT and g-GGT are markers of cholestatic hepatobiliary diseases. 31 The alb-GGT isoform has been demonstrated in the sera of patients with primary or metastatic liver tumors 30 (Fig. 1).…”

“…The presence of alb‐GGT in the serum was not 100% specific for HCC because it was also found in most of the patients with MLD and in a few of those from the CIR group as well. Considering the widespread distribution of GGT in normal tissues, it is not surprising that tumor‐associated isoforms are encountered in patients with various forms of malignancy 21,25 , 31 . In fact, the MLD patients with serum alb‐GGT had primary tumors of the pancreas (three cases), colon (two cases), stomach (one case), biliary system (one case) or of unknown origin (two cases).…”

“…distinguishes five electrophoretic isoforms named according to the serum protein fractions that comigrate with them: alb‐GGT, α1‐GGT, α2‐GGT, β‐GGT, and γ‐GGT 28 . Both α1 and α2‐GGT are usually found in normal subjects, 39 while β‐GGT and γ‐GGT are markers of cholestatic hepatobiliary diseases 31 . The alb‐GGT isoform has been demonstrated in the sera of patients with primary or metastatic liver tumors 30 (Fig.…”

“…In the 1980s, an Italian group developed an electrophoretic procedure for the analysis of GGT isoenzymes. Of the five different isoenzymatic bands that could be distinguished, the one that comigrates with serum albumin (alb‐GGT) appeared to be promising for the diagnosis of both primary and secondary liver tumors 28–31 . Therefore, the aim of this study was to evaluate the usefulness of the alb‐GGT assay for detection of HCC in a large cohort of Western cirrhotic patients, and to compare the results obtained with that of the serum AFP assay.…”