Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with a poor prognosis. Recently, we established a HCC cell line from a metastatic HCC tumor. GTG banding analysis was performed and the karyotype showed that this metastatic HCC cell line is a hypertriploid (71-78 chromosomes) with a large marker chromosome containing a long homogeneously staining region (hsr). Comparative genomic hybridization was applied to characterize the chromosomal alterations in this metastatic HCC cell line. The results showed that the hsr was composed of amplified DNA sequences from 11q13. Further characterization of the hsr may lead to the isolation of the putative amplified oncogene at 11q13.

Aims: To examine the expression of ADAM12 (meltrin a), a member of the disintegrin and metalloprotease (ADAM) family, in human giant cell tumours of the bone, skeletal muscle tissue from human embryos, and human adult skeletal muscle tissue. Methods: ADAM12 mRNA was detected by reverse transcription polymerase chain reaction and in situ hybridisation. Results: ADAM12 mRNA was detected in 14 of the 20 giant cell tumours of bone and in three of the six tumour cell cultures. The expression of ADAM12 in cells cultured from the tumour was linked to the presence of multinucleated giant cells. ADAM12 mRNA could not be detected in the five adult skeletal muscle tissue samples, although it was found in the two embryonic skeletal muscle tissue samples. ADAM12 mRNA was localised to the cytoplasm of multinucleated giant cells and some mononuclear stromal cells. Conclusions: These results indicate that multinucleated giant cells are formed by the cell fusion of mononuclear stromal cells in giant cell tumours of bone and that ADAM12 is involved in the cell fusion process.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world with a very poor prognosis that has been associated with tumor metastasis. The molecular mechanism of HCC metastasis is still unclear. In this study, we established cell lines from a primary tumor (H2-P) and its metastatis (H2-M). G-banding karyotyping, comparative genomic hybridization, and fluorescence in situ hybridization were applied to study these two cell lines and the results demonstrated that they are of the same origin. These cell lines provide a very useful tool to identify genetic alterations associated with HCC metastasis.

The poor prognosis of hepatocellular carcinoma (HCC) has been associated with recurrence and metastasis. Recently, we established a pair of HCC cell lines from a primary (H2-P) and its matched metastatic (H2-M) HCC tumors. A high density of cDNA microarray with 9184 human cDNA was used to identify the differentially expressed genes between H2-P and H2-M. Comparing with H2-P, eight upregulated and six downregulated genes were detected in H2-M. One interesting finding is the overexpression of Vimentin (VIM), a well-defined intermediate filament,whi ch has been linked to a more aggressive status in various tumors. The correlation of overexpression of VIM and HCC metastasis was studied by immunohistochemistry using a tissue microarray with 200 primary HCCs and 60 pairs of primary and matched metastatic HCC samples. Tissue microarray demonstrated that the overexpression of VIM was significantly associated with HCC metastasis (Po0.01). This finding strongly suggests that the overexpression of VIM may play an important role in the metastasis of HCC.

AIM: To investigate the expression pattern of clusterin in colorectal adenoma-carcinoma-metastasis series, and to explore the potential role of clusterin in multistage colorectal tumorigenesis and progression. METHODS: A colorectal carcinoma (CRC)-tissue microarray (TMA), which contained 85 advanced CRCs including 43 cases of Dukes B, 21 of Dukes C and 21 of Dukes D tumors, were used for assessing the expression of clusterin (clone 41D) and tumor cell apoptotic index (AI) by immunohistochemistry and TUNEL assay, respectively. Moreover the potential correlation of clusterin expression with the patient’s clinical-pathological features were also examined. RESULTS: The positive staining of clusterin in differentcolorectal tissues was primarily a cytoplasmic pattern. Cytoplasmic overexpression of clusterin was detected in none of the normal colorectal mucosa, 17% of the adenomas, 46% of the primary CRCs, and 57% of the CRC metastatic lesions. In addition, a significant positive correlation between overexpression of clusterin and advanced clinical (Dukes) stage was observed (P<0.01). Overexpression of cytoplasmic clusterin in CRCs was inversely correlated with tumor apoptotic index (P<0.01), indicating the antiapoptotic function of cytoplasmic clusterin in CRCs. CONCLUSION: These data suggests that overexpression of cytoplasmic clusterin might be involved in the tumorigenesis and/or progression of CRCs. The anti-apoptotic function of cytoplasmic clusterin may be responsible, at least in part, for the development and biologically aggressive behavior of CRC.