Cancer of the bladder is a frequent malignancy in Egypt and other developing countries in which bladder infection with the parasite Schistosoma haematobium is common. Several epidemiological, histopathological and clinical characteristics of cancer of the Bilharzial bladder suggest that it is distinct from bladder cancer seen in industrialized countries. Little is known, however, about molecular aberrations in Egyptian bladder cancer. We studied the status of p53 in a series of 25 cases of Egyptian bladder cancer using immunohistochemistry to detect the p53 protein and SSCP/sequencing to identify mutations in the p53 gene. Ten of 25 (40%) tumor samples showed a mutation by SSCP/sequencing. Mutations were seen in both the squamous and transitional cell variants. The presence of mutations was associated with advanced stage of disease. Immunohistochemistry had a sensitivity of 70%, and a specificity of 85% for detecting p53 mutations. Our data show that p53 mutations are a common event in Egyptian bladder cancer, and may be an indicator of advanced disease. Immunohistochemistry is both sensitive and specific for detecting p53 mutations in this tumor, and may be used to assess the prognostic value of p53 mutations in this disease.

BACKGROUND: The mechanisms underlying de-novo hepatocellular carcinoma (HCC) after direct-acting antivirals (DAAs) is still under investigation. This work aims to study P53 and hepatocyte growth factor (HGF) as possible diagnostics of de-novo hepatocellular carcinoma (HCC) following DAAs in comparison to alpha-fetoprotein (AFP).

METHOD: This case-control study included 166 patients with liver cirrhosis divided into group-1: patients without HCC (n = 50), group-2: patients with de-novo HCC following DAAs, and achieved sustained virological response (n = 50), and group-3: patients with HCC without DAAs (n = 66). P53 antibody and HGF were determined using a quantitative sandwich enzyme immunoassay technique (Cusabio Co, Houston, USA).

RESULTS: Patients with HCC showed significantly higher HGF. Patients with de-novo HCC following DAAs had significantly higher P53 than HCC without DAAs (P < 0.0001). The multiple logistic regression analysis showed that the P53 levels were significantly associated with susceptibility to de-novo HCC (P value = 0.004). The best overall formula was constructed for HCC diagnosis by entering significant markers into the regression model. A three markers model was developed = (1.22 + AFP X 0.002 + HGF X 0.001 + P53 X 0.001). The medians (percentiles) of combined three markers were 1.8 (1.0-2.1) in liver cirrhosis and 2.2 (2.0-2.9) in all HCC (P < 0.00001). The AUC of combined markers was greater than a single marker. The AUC was 0.87 to differentiate HCC from liver cirrhosis; AUC 0.91 to differentiate de-novo HCC after DAAs from liver cirrhosis.

CONCLUSION: P53 may serve as a diagnostic marker for de-novo HCC after DAAs therapy. HGF may serve as a diagnostic marker for HCC but not specific for de-novo HCC after DAAs therapy.

Several studies have indicated that wild type p53 plays an important role in controlling cell growth and acts as a cyclin modifier. Abnormalities in p53 induce the overexpression of proliferating cell nuclear antigen. The aim of this study is to correlate immunocytochemically the expression of mutant p53 and the proliferative index (PI) as indicated by image analysis of PCNA immunoreactivity in 81 cases of pleural and peritoneal effusions. There was a strong correlation (r = 73%) between p53 immunoreactivity and PCNA PIs. Forty-three (71%) cases indicated p53 immunostaining out of 61 cases with PCNA immunoreactivity, forty of which (93%) proved to have a diagnosis of malignancy using histological or clinical data. Furthermore, 7 malignant cases showed PCNA reactivity but no p53 immunostaining. An additional four malignant cases indicated no reactivity for either p53 or PCNA. Also, there was a significant difference in the PCNA PI between benign and malignant effusions (p < 0.001). These clinical observations confirm the function of wild p53 as a check point during cell cycling, and as a strong negative feedback effect on PCNA expression. Furthermore, such co-expression represents a significant indicator for malignancy.

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