ADRIAN GOLDIS, RAMONA GOLDIS, MARIOARA CORNIANU, NORINA BASA, DANIELA LAZAR, AMADEUS DOBRESCU, FULGER LAZAR IMMUNOHISTOCHEMICAL STUDY OF CELL PROLIFERATION IN HEPATOCELLULAR CARCINOMA Hepatocellular carcinoma (HCC), the most common primary liver cancer, with a poor prognosis, is the fifth most common cancer in men and the seventh in women. The study was made on 32 surgically removed liver carcinomas. In order to compare results, we included a group of non-tumor lesions obtained by liver biopsy. Assessment of the proliferative activity of the studied liver lesions was made using immunohistochemical stains with the monoclonal Ki-67 antibody, clone MIB-1 ready-to-use (DAKO Cytomation CA, USA), in the LSAB-HRP work system. To appreciate the proliferation index of Ki-67 (PI Ki-67), we used the semi-automated method of counting the nuclei on digital images. The statistical analysis was performed using SPSS software, Version 20.0 (IBM SPSS Statistics) and Microsoft Office Excel 2007. Mean value of Ki-67 index was 0.4 ± 0.2 in normal liver, 3.52 ± 0.2 in non-tumor liver lesions and 13.4±7.7 in HCC (p < 0.001). In chronic hepatitis, PI Ki-67 varied between 2.5 and 5.8 %, with a mean value of 5.2% in portal chronic hepatitis and 5.5% in active chronic hepatitis with cirrhotic evolution. In HCC, the values of Ki-67 index were between 0.7% and 52%, with a mean of PI Ki-67 of 13.43±7.7. 66.6% of HCC associated with hepatitis B virus infection and those developped from a cirrhotic lesion had a high Ki-67 score (p = 0.1). The results we obtained showed: a low Ki-67 score in patients with well-differentiated HCC (G1) (p<0.001), with or without capsule infiltration (p = 0.003); high PI Ki-67 in 33.33% of HCC detected in the right hepatic lobe and those extended bilaterally at the moment of diagnosis (p = 0.142) and a significant relationship between high Ki-67 score and vascular invasion (p < 0.001), the presence of intrahepatic metastasis being correlated with a high proliferative rate (p < 0.001). Differences between the proliferation rate of HCC and non-tumor liver lesions (p < 0.001) show that the uncontrolled division of tumor cells can play an important role in the developpment of HCC.
Keywords: hepatocellular carcinoma, proliferation index of Ki-67, immunohistochemistry