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

Abstract

The amplification and/or rearrangement of the cyclin D1 gene, a positive regulatory 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 this study, we investigated the expression of cyclin D1 in the formalin-fixed and paraffin-embedded human hepatocellular carcinoma (HCC) tissues of 25 patients, using monoclonal antibody 5D4 raised against cyclin D1. Two distinct patterns of staining were observed in HCC cells, nuclear and cytoplasmic. The nuclear staining pattern of cyclin D1 was detected in the tissues of only 2 of the 25 HCC patients (8%) examined and no particular clinicopathological characteristics were found in these patients. In contrast, the cytoplasmic 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 the portal vein (Vp), as well as those with intrahepatic metastasis (IM). These 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 immunohistochemical 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 suggest that cyclin D1 is expressed later than the alteration of p53 in the progression of human HCC.

Impact of differential cyclin D1 expression and localisation in prostate cancer

“…In pituitary (Hibberts et al, 1999;Simpson et al, 2001) and ovarian (Dhar et al, 1999) tumours, cytoplasmic cyclin D1 has been reported (35 and 59% of cyclin D1-positive cases, respectively) but no correlations were identified. In hepatocellular carcinomas, cytoplasmic cyclin D1 appeared to significantly correlate with prognostic factors like intrahepatic metastasis (Sato et al, 1999). A large study which assessed cyclin D1 localisation was performed with 150 transitional cell carcinomas of the bladder, wherein cytoplasmic cyclin D1 increased with disease progression and correlated with decreased survival (Tut et al, 2001).…”

Up-regulation of Cyclin D1 by HBx Is Mediated by NF-κB2/BCL3 Complex through κB Site of Cyclin D1 Promoter

“…HCC (37). Recent data suggest that HBx-mediated cyclin D1 up-regulation in mammary gland cells can induce tumors as well despite the differences between hepatocyte and mammary gland cells (18).…”

Identification, using cDNA macroarray analysis, of distinct gene expression profiles associated with pathological and virological features of hepatocellular carcinoma

“…The heterogeneity of our macroarray pattern did not result from individual genetic variations, since we compared tumour and non-tumour Hierarchical clustering and cDNA macroarray-based analyses allowed us to identify a number of potential gene networks which were deregulated in the context of liver carcinogenesis. Some of these genes, such as betacatenin, p53, TGF-beta and genes involved in G1/S transition, have previously been incriminated in HCC or the development of other cancers (Abou-Shady et al, 1999;Buendia, 2000;Ito et al, 1999;Sato et al, 1999;Vousden, 2000;Wong et al, 2001;Yuspa et al, 1994). In addition, our analysis has highlighted other regulatory pathways which may be of importance to our understanding of liver carcinogenesis.…”