Evidence of Disruption of p53 and Glutathione S Transferase Pi in Extrahepatic Biliary Atresia in Association with Neutrophil Elastase Mediated Damage
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- Category: Vol. 83, March 2015
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Evidence of Disruption of p53 and Glutathione S Transferase Pi in Extrahepatic Biliary Atresia in Association with Neutrophil Elastase Mediated Damage, MAGD A. KOTB
Abstract
Background: Extrahepatic biliary atresia (EHBA) is a chronic obstructive cholangiopathy of infancy with obscure aetiology. I recently reported unanimous strong immunohis-tochemical staining against neutrophil elastase in EHBA liver biopsies, with variable degrees of fibrosis, and variable CD14+ monocytes intensity staining. Neutrophil inflicted cellular damage is a crucial step for regeneration by removal of cells that are unwanted, damaged or that do not demonstrate DNA fidelity. Cellular p53 and glutathione S transferase (GST) govern the ontogeny respected regeneration. EHBA is not a self-limiting condition despite fulfilling the neutrophil inflicted cellular damage step, and healing by regeneration results in cirrhosis. This necessitated further investigation of these biopsies for involvement of p53 that is responsible for DNA fidelity at cellular replication and regeneration and GST that is responsible for detoxification of a wide array of substances that affect cellular replication and DNA fidelity.
Aim of Work: Is to study p53 and GSTPi in EHBA.
Material and Methods: The liver biopsies of 32 neonates and infants with EHBA were studied by immunohistochemical staining for p53 and class Pi of GST family. The biopsies were collected percutaneously using Menghini needles. The findings were correlated to previously studied parameters: Fibrosis, neutrophil infiltration, staining against neutrophil elastase and staining for anti-CD14+ monocytes. Study com-menced by October, 1999 till October, 2002, in New Children Hospital, Cairo University.
Results: All 32 biopsies (100%) demonstrated defective staining of p53 and GSTPi. Mean ± SD percentage of p53 staining was 30.37±9.6% (range 12-46%). 25 (78.1%) did not stain for GSTPi, and 7 (21.9%) stained mildly. GST Pi staining did not correlate with other biopsy findings or prognosis. Staining of p53 correlated with neutrophil infiltration (p=0.001), fibrosis (p=0.026) and anti CD14+ staining (p=0.000), but not to outcome. Negative correlation between staining for p53 and resolution of symptoms did not amount to statistical significance (p=0.068).
Conclusion: Involvement of p53, GSTPi, CD14+ mono-cytes and neutrophil elastase in EHBA is unanimous. Their contribution to aetiology or to notorious chronic progressive course of EHBA remains to be defined.