It has been suggested that the number of argyrophilic nucleolar organi
zer regions (AgNORs) correlates with cellular activity and the aggress
iveness of malignancy. The mean number of AgNORs per nucleus may, ther
efore, be a prognostic factor for hepatocellular carcinoma (HCC). The
purpose of this study was to evaluate the prognostic significance of t
he number of AgNORs in HCC. The silver-staining technique was applied
to surgically resected specimens to indicate AgNORs. Eighty-nine of th
e specimens were of HCC, 23 were of normal liver adjacent to HCC, and
32 were of cirrhotic liver adjacent to HCC. The number of AgNORs of HC
C (mean +/- SD, 3.26 +/- 1.23) was significantly higher than those of
normal liver (1.37 +/- 0.13) and cirrhotic liver (1.49 +/- 0.14). The
number of AgNORs was significantly correlated with serum alpha-fetopro
tein level, tumor size, portal vein invasion, and Edmondson-Steiner hi
stological grade. In patients undergoing curative resection, the survi
val rate of those with a high number (>3.04) of AgNORs was significant
ly worse than that of those with a low number (less than or equal to 3
.04) of AgNORs. Multivariate analysis showed that the number of AgNORs
was a significant variable when all patients undergoing curative rese
ction were assessed together. The results of this study suggest that t
he number of AGNORs is useful as an indicator of the grade of malignan
cy and as a predictor of the prognosis of patients with HCC who do not
have portal vein involvement.