Association of cyclin D1 expression with factors correlated with tumor progression in human hepatocellular carcinoma

The amplification and/or rearrangement of the cyclin D1 gene, a positive re gulatory element of the G1 to S phase, of the cell cycle, has been reported in various human tumors, suggesting an oncogenic role of this gene. In thi s study, we investigated the expression of cyclin D1 in the formalin-fixed and paraffin-embedded human hepatocellular carcinoma (HCC) tissues of 25 pa tients, using monoclonal antibody 5D4 raised against cyclin D1. Two distinc t patterns of staining were observed in HCC cells, nuclear and cytoplasmic. The nuclear staining pattern of cyclin D1 was detected in the tissues of o nly 2 of the 25 HCC patients (8%) examined and no particular clinicopatholo gical characteristics were found in these patients. In contrast, the cytopl asmic staining pattern, without nuclear staining, was detected in 8 of the 25 patients with HCC (32%). A significant correlation was found between the expression of cytoplasmic cyclin D1 and patients with tumor thrombus in th e portal vein (Vp), as well as those with intrahepatic metastasis (IM). The se results indicate that the cytoplasmic cyclin D1 expression appears to be related to the prognosis of HCC. The Ag nucleolar organizer regions (NORs) counts in cyclin D1-positive and -negative patients were not significantly different, suggesting that immunostaining for cyclin D1 has the potential to be a unique prognostic marker in human HCC. Simultaneous immunohistochem ical study with p53 antibody in the same series of HCC revealed that 88% of the patients positive for cyclin D1 also expressed p53 and that in 91% of the patients negative for p53, cyclin D1 was not expressed. These results s uggest that cyclin D1 is expressed later than the alteration of p53 in the progression of human HCC.