RESUMO
Background: Recent studies have raised the possibility that EBV may be involved in the pathogenesis of breast carcinoma. Many studies have shown that membrane type-1 matrix metalloproteinase [MT1-MMP] has an important role in matrix metalloproteinase type2 [MMP-2] activation in cell membranes but only few reports about its clinical value are valid. In this study, we investigated the relationship between MT1-MMP protein expression and MMP2 activity as well as EBV infection
Materials and Methods: 34 cases of infiltrating duct carcinoma were collected. MT1-MMP protein expression was detected by Western Blot, MMP2 by Zymographic analysis and EBV DNA was determined by PCR. Also, latent membrane protein type 1 [LMP1] of EBV, estrogen receptor [ER], and human epidermal growth factor receptor 2 [Her-2] were measured immunohistochemically
Results: The results revealed that EBV-DNA was found in 12 cases [35.3%] while only 6 control samples [17.6%] were positive for viral DNA. The latent EBV protein LMP-1 was detected in 6 cases and in 2 cases of control samples. MT1-MMP expression was found in 79.4%, while it was 26.4% in the normal surrounding tissues [p-value <0.001]. There was a significant association between MT1-MMP expression and MMP-2 activity [p-value = 0.007] in the tumor tissue. Also, ER was observed in 13 /34[38.2%] cases, while Her-2 overexpression was detected in 19 /34 [55.9%] cases
Conclusion: This study suggests an association between EBV and infiltrating duct carcinoma of female breast regarding tumor development and aggressiveness. Also, MT1-MMP can be used as a prognostic factor predicts the possibility of breast cancer invasion and metastasis
RESUMO
Background: Chronic HBV and HCV infections are the major risk factors for the development of HCC through a multistep pathway that involves viral and non-viral dependent pathophysiological steps. Hepatic expression of the nuclear proliferative marker ki-67 and the p53 oncoprotein were found to be associated with poor outcome. So, the present study was done to evaluate the changes in expression of Ki-67 and p53 oncoprotein, and to determine p53 gene mutation in HBV/HCV-related HCC Egyptian patients
Materials and Methods: Eight HBV-and 22 HCV-positive HCC cases have been examined for the presence of p53 mutation by immunohistochemistry [IHC] and single-strand conformation polymorphism [SSCP] followed by direct DNA sequencing. HCV were genotyped by LiPA-II
Results: Our results have shown that the proliferative marker ki-67 LI and p53 were highly expressed and significantly related to tumor grade in the Egyptian HCC cases [p<0.05]. Also, p53 mutation was found in 16 HCC cases by IHC and in 14 HCC cases by SSCP, only 11 patients showed p53 mutation by sequencing. The highest mutation rate was scored for exon 7 [7 mutations] at codon 249; 4 out of 8 [50%] of HBV-related HCC cases and 3 out of 22 [13.6%] of HCV-related HCC cases, followed by exon 5 [3 mutations] at codons 133, 146, 176 in HCV-related HCC cases, then exon 8 at codon 275 in HCV-related HCC cases. The concordance between the IHC and sequencing analysis was 69%
Conclusion: the present study demonstrates the association between the proliferative marker ki-67 and p53 expression with the tumor grade of Egyptian HBV/HCV-related HCC cases. Our results also support the hypothesis that p53 mutations are rather a late event in the carcinogenesis. Also, they suggest that the final steps of hepatocarcinogenesis are common and independent of the aetiology of the viral infection