ABSTRACT
Cyclooxygenase-2, the inducible rate-limiting enzyme of prostaglandins biosynthesis, has been reported to be involved in the pathogenesis of a variety of chronic inflammation-related human malignancies including Hepatocellular Carcinoma [HCC]. However, its clinical significance in HCC remains obscure. Our objectives were to evaluate COX-2 expression in HCC and correlate its expression to the different clinicopathological parameters and to assess its impact on patient survival. The present study was conducted on 17 HCC and 21 adjacent non-tumor liver tissues obtained from 22 HCC patients underwent curative hepatectomy at the National Cancer Institute, Cairo University, Egypt. Eight normal liver tissues taken from normal donors and HepG2 cell line were used as controls. Total RNA from tissues and cells was extracted and COX-2 mRNA was detected by RT- PCR and correlated to the clinicopathological criteria as well as to patient's survival. COX-2 mRNA was detected in 58.8% of the HCC tissues and in 28.6% of the adjacent non-tumor liver tissues. COX-2 expression was significantly associated with elevated levels of serum aspartate aminotransferase [AST] with high specificity for the detection of the disease. However, there was no significant correlation between COX-2 expression and any of the histopathological criteria. COX-2 expression may be involved in HCC carcinogenesis with high specificity for the detection of the disease It was significantly associated with elevated AST levels indicating disease severity. However cox2 expression seems to be an independent factor with no correlation to any of the clinicopathological data or patient's survival
ABSTRACT
DNA mismatch repair [MMR] is an important mechanism involved in maintaining fidelity of genomic DNA. Abnormalities in at least one of five MMR genes are implicated in the development of many cancers and the associated micro satellite instability [MSI]. By using a newly developed multiplex reverse transcription -PCR assay, the expression of the five known MMR [hMLH1, hPMS1, hPMS2, GTBP/hMSH6, hMSH2] were evaluated in 33 human HCC cases as well as 16 cases from the normal distant hepatic tissue samples [NDHT] were also evaluated. Twenty- five of them were associated with HCV infection. This was done in an attempt to determine the role of MMR genes in the development of HCC. The beta actin gene was used as an internal control for RNA degradation and DNA contamination and as well as a reference for quantifying the levels of their transcription. Out of the 33 studied HCC cases, 30 cases [90.9%] showed reduction in the expression of one or more of the 5 studied MMR genes. Reduced expression of hMSH2 was found in [71.9%], hMLH1 [53.3%], GTBP [51.1%], hPMS2 [33.3%] and hPMSI [6%]. Correlation analysis showed a strong significant correlation [P= 0.0069] between reduced expression of hPMS2 and GTBP [P=0.0034] as well as hPMS2 and non-cirrhosis [P=0.0197]. Chi-square analysis showed a significant correlation between reduced expression of hMLHl and grade II. On the other hand, 57.1%, 50%, 20%, 18.8% and 6% of the NDHT showed reduced expression of hMSH2, hMLHI, GTBP, hPMS2 and hPMSI respectively. Multivariate analysis showed significant correlation between HCC and hMSH2 [P= 0.008], hMLH1 [P=0.001] and GTBP [P=0.032], also between hPMS2, GTBP and HCC infected with HCV cases [P< 0.001, 0.002]. It could finally be concluded that reduced expression of hPMS2 is likely associated with growth advantage and stimulates proliferation changes that have encouraged malignant development in non- cirrhotic HCV infected patients via acquisition of more genetic damage and the MMR defects that occur at an early stage of hepatocarcinogenesis