In hepatocellular carcinoma AgNOR protein expression correlates with tumour mass doubling time

Aims/Methods: The relationship between AgNOR protein expression and doubling time was evaluated in 20 untreated nodules of hepatocellular carcinoma arising in cirrhotic liver. AgNOR protein quantity within the lesion was defined by image cytometry on histological sections from frozen biopsies obtained under ultrasound-guidance, selectively stained for AgNOR proteins. Tumour doubling time was calculated 6 months after diagnosis by measuring the volume variations of the nodules over a fixed period by “real time” ultrasonography. Results: The doubling time of nodules characterized by high AgNOR protein area values ( > 5.50 μm2, corresponding to the median AgNOR protein value) was shorter than that of nodules with low AgNOR protein area values (<5.50 μm2). A highly significant difference in the mean doubling time values between the two groups (6.31±2.68 (E.S.) versus 15.92±3.03 (E.S.) months, respectively; p=0.009) was found. Moreover, when the relationship between AgNOR protein and doubling time values was tested by linear regression analysis, a significant inverse correlation was observed (r=−0.68; p<0.005). Conclusions: Our results indicate that AgNOR protein quantity represents a reliable parameter for predicting the tumour growth rate of untreated hepatocellular carcinoma nodules. Among the procedures commonly employed for the assessment of cell proliferation, the evaluation of the AgNOR parameter seems to be particularly suitable for kinetic analysis of ultrasound-guided fine-needle liver biopsies.