p21/Wafl/Cipl cellular expression in chronic long-lasting hepatitis C: correlation with HCV proteins (C, NS3, NS5A), other cell-cycle related proteins and selected clinical data.

Studies indicate that proteins of hepatitis C virus (HCV) disturb expression of cell-cycle-related proteins. A disturbed cell-cycle control is a hepatocellular carcinoma (HCC) risk factor in patients with HCV-related liver damage. The present study aimed to analyse the cellular expression of p21/Wafl/Cipl (p21) in long-lasting chronic hepatitis C (CH-C), its correlation with the key oncogenic HCV proteins (C, NS3, NS5A), other cell-cycle-related proteins (PCNA, Ki-67, cyclin D1, p53) and selected clinical data. Archival liver biopsies, obtained from patients with CH-C, normal livers, and hepatocellular carcinoma (HCC) specimens were analysed by immunocytochemistry and ImmunoMax technique. In CH-C overexpression of p21 protein was demonstrated. Positive correlations of p21 protein expression in CH-C involved age of the patients, grading, and liver steatosis. Moreover, expression of p21 correlated significantly with expression of p53 protein, of D1 cyclin and Ki-67. Although Ki-67 antigen was related to p21 expression, only Ki-67 expression proved to be directly related to liver staging. Expression of the NS3 protein, which prevailed in CH-C patients, manifested correlation with p21 expression, and that of cyclin D1. In presence of preserved potential for regeneration, overexpression of p21 indicates inhibition of cell cycle in hepatocytes, which probably plays a protective role for the chronically damaged cells. Out of the three HCV proteins only NS3 seems to affect control of p21 protein expression in in vivo infection. Nevertheless, the studies indicate that neither expression of p21 protein nor that of viral NS3 protein can serve as a marker of progression of CH-C to HCC in vivo

p53 immunocytochemistry and TP53 gene mutations in patients with chronic hepatitis C virus (HCV) infection.

Chronic infection with hepatitis C virus (HCV) is regarded as a risk factor for hepatocellular carcinoma (HCC), mostly in patients with liver cirrhosis. Present study aimed at evaluation of cellular expression of p53 protein, genetic TP53 changes in liver samples and anti-p53 in serum of patients with chronic hepatitis C virus infection. The expression of p53 protein were analysed by immunocytochemistry in liver biopsies from adult patients with chronic, long-lasting hepatitis C. In order to detect TP53 mutations, PCR/SSCP and sequencing were performed. Antibodies against p53 in serum were determined using enzyme immunoassay (ELISA).In two out of 14 examined patients TP53 point mutations were detected in the liver samples. In the first patient, a substitution of C to T was demonstrated in position 1 of the codon 250, resulting in substitution of proline by serine. The other patient carried a substitution of C to G in position 13274 of the intron 6. The patient carrying mutation in the codon 250 demonstrated morphological traits of liver cirrhosis and had high number of p53-immunoreactive cell nuclei in tissue. None of the patients manifested elevated titres of serum anti-p53. In the liver, significant positive correlations were disclosed between expression of p53 on one hand and grading and staging on the other. A negative correlation was disclosed between cellular expression of p53 and duration time of infection. In conclusions, genetic changes in TP53 can be detected also in non-neoplastic lesions linked to chronic HCV infection

Tissue expression of S100 proteins in gallbladder mucosa of the patients with calculous cholecystitis

 Proteins of S100 group, produced by phagocytes represent endogenous activators of innate immune responses. Role of these proteins in the etiopathogenesis of cholelithiasis remains unknown. The studies aimed at the morphometric evaluation of S100A8 and S100A9 protein expression in gallbladder mucosa in patients with acute and chronic calculous cholecystitis (n = 71). The presence of proteins was detected by immunohistochemistry while quantitative analysis employed the spatial visualization technique. We found the immunopositive expression of the two studied S100 proteins in neutrophils and monocytes/macrophages of the gallbladder’s wall and a higher expression in acute cholecystitis. Quantitative study revealed higher immunoexpression of S100A9 over S100A8 in both studied groups of patients. Moreover, a reciprocal linear relationship between the expression of the studied proteins and a positive correlation between expression of either S100A8 or S100A9 and inflammatory activity (grading) in the gallbladder wall were found. The expression of S100A8 protein in the chronic cholecystitis group and in older patients correlated with leukocytosis, which suggests the role of S100A8 particularly at the chronic stage of cholecystitis. The obtained results indicated close relationship between S100A8 and S100A9 proteins in their proinflammatory functions. The increased expression of only one of them can be recognized as a useful index of local inflammatory activity in calculous cholecystitis.

p21/Wafl/Cipl cellular expression in chronic long-lasting hepatitis C: correlation with HCV proteins (C, NS3, NS5A), other cell-cycle related proteins and selected clinical data.

Studies indicate that proteins of hepatitis C virus (HCV) disturb expression of cell-cycle-related proteins. A disturbed cell-cycle control is a hepatocellular carcinoma (HCC) risk factor in patients with HCV-related liver damage. The present study aimed to analyse the cellular expression of p21/Wafl/Cipl (p21) in long-lasting chronic hepatitis C (CH-C), its correlation with the key oncogenic HCV proteins (C, NS3, NS5A), other cell-cycle-related proteins (PCNA, Ki-67, cyclin D1, p53) and selected clinical data. Archival liver biopsies, obtained from patients with CH-C, normal livers, and hepatocellular carcinoma (HCC) specimens were analysed by immunocytochemistry and ImmunoMax technique. In CH-C overexpression of p21 protein was demonstrated. Positive correlations of p21 protein expression in CH-C involved age of the patients, grading, and liver steatosis. Moreover, expression of p21 correlated significantly with expression of p53 protein, of D1 cyclin and Ki-67. Although Ki-67 antigen was related to p21 expression, only Ki-67 expression proved to be directly related to liver staging. Expression of the NS3 protein, which prevailed in CH-C patients, manifested correlation with p21 expression, and that of cyclin D1. In presence of preserved potential for regeneration, overexpression of p21 indicates inhibition of cell cycle in hepatocytes, which probably plays a protective role for the chronically damaged cells. Out of the three HCV proteins only NS3 seems to affect control of p21 protein expression in in vivo infection. Nevertheless, the studies indicate that neither expression of p21 protein nor that of viral NS3 protein can serve as a marker of progression of CH-C to HCC in vivo

p53 immunocytochemistry and TP53 gene mutations in patients with chronic hepatitis C virus (HCV) infection.

Chronic infection with hepatitis C virus (HCV) is regarded as a risk factor for hepatocellular carcinoma (HCC), mostly in patients with liver cirrhosis. Present study aimed at evaluation of cellular expression of p53 protein, genetic TP53 changes in liver samples and anti-p53 in serum of patients with chronic hepatitis C virus infection. The expression of p53 protein were analysed by immunocytochemistry in liver biopsies from adult patients with chronic, long-lasting hepatitis C. In order to detect TP53 mutations, PCR/SSCP and sequencing were performed. Antibodies against p53 in serum were determined using enzyme immunoassay (ELISA).In two out of 14 examined patients TP53 point mutations were detected in the liver samples. In the first patient, a substitution of C to T was demonstrated in position 1 of the codon 250, resulting in substitution of proline by serine. The other patient carried a substitution of C to G in position 13274 of the intron 6. The patient carrying mutation in the codon 250 demonstrated morphological traits of liver cirrhosis and had high number of p53-immunoreactive cell nuclei in tissue. None of the patients manifested elevated titres of serum anti-p53. In the liver, significant positive correlations were disclosed between expression of p53 on one hand and grading and staging on the other. A negative correlation was disclosed between cellular expression of p53 and duration time of infection. In conclusions, genetic changes in TP53 can be detected also in non-neoplastic lesions linked to chronic HCV infection