Clinical importance of p53 protein in gall bladder carcinoma and its precursor lesions.

Abstract

Aims-To study the expression and importance (if any) of p53 protein in gall bladder carcinoma and its precursor lesions. Methods-Immunohistochemical staining was performed on formalin fixed, paraffin wax embedded histological sections with an anti-human p53 monoclonal antibody (DO-7; Dako Corporation M7001) (24 carcinomas, one adenocarcinoma in situ, six dysplasias, three adenomas and four cases of chronic cholecystitis). Invasive, in situ, and dysplastic areas as well as normal-looking epithelium were sought. Nuclear Carcinogenesis is a multistep process involving several genetic changes which include activation of cellular proto-oncogenes and inactivation of tumour suppressor genes.7Invasive carcinomas of the gall bladder are often associated with dysplasia and adenocarcinoma in situ changes in the neighbouring epithelium. This association implies a temporal progression or radical change in the process of carcinogenesis and provides a good sequential model for studying the evolution of p53 protein expression in the malignant transformation of gall bladder epithelium. MethodsTwenty four carcinomas of the gall bladder, one adenocarcinoma in situ, six epithelial dysplasias, three adenomas and four cases of chronic cholecystitis were retrieved from the files of the department of pathology, National University Hospital. All the tissue had been fixed in 10% buffered formalin and embedded in paraffin wax. Slides stained with haematoxylin and eosin and periodic acid-Schiff before and after diastase digestion were evaluated. The cases were analysed for invasive, in situ, and dysplastic areas as well as normallooking epithelium.Immunohistochemical staining was performed using a streptavidin-biotin immunoperoxidase method. Waxed sections (4 im) were treated with 3% hydrogen peroxide for 10 minutes to block endogenous peroxidase. The sections were then incubated with 5% bovine serum albumin (BSA) in TRISbuffered saline (TBS) for 30 minutes to eliminate any non-specific staining. Excess BSA was drained from the slides before incubation with an anti-human p53 monoclonal antibody (DO-7; Dako Corporation M7001) at an optimal dilution of 1 in 50 in 0-1% BSA overnight at 4°C. The tissue sections were subsequently washed with TBS and incubated with biotinylated rabbit-anti-mouse immunoglobulin (Dako; E354), 1 in 200 in 0-1% BSA

p27Kip1 expression in normal epithelia, precancerous lesions, and carcinomas of the gallbladder: Association with cancer progression and prognosis

“…Because p53 inactivation and K-ras activation have been shown in GBC precursor lesions of adenoma and epithelial dysplasia, they are considered to be early events in gallbladder carcinogenesis, playing a role in transforming precancerous lesions to cancers. [1][2][3][4][5][6] However, these alterations do not appear to influence or reflect the clinical properties of GBC. 5,6 Activation of oncogene c-erbB-2 has also been shown in GBCs; however, its clinical significance has not been clarified.…”

“…Tumor suppressor gene p53 inactivation and oncogene K-ras activation have been characterized as early events in gallbladder carcinogenesis; however, these alterations have not been associated with GBC progression and prognosis. [1][2][3][4][5][6] In mammalian cells, transition from the G1 into the S phase is governed by cyclin-dependent kinases (CDKs), which are activated by binding of positive effectors, the cyclins, and inhibited by CDK inhibitors. 7 CDK inhibitors fall into two families, INK and CIP/KIP, on the basis of sequence homology.…”

Predictive value of p53 and pRb expression in superficial bladder cancer patients treated with BCG and interferon‐alpha

“…Unlike many studies, we also took into account the intensity of immunoreactivity for both p53 and pRb, consistent with other studies that have evaluated their expression abnormalities in organ systems other than bladder cancer. [32][33][34][35][36][37][38] The final composite score comprised both extent and intensity components. We believe that this composite scoring system, together with the assignment of a narrower range for p53 overexpression (score 4-6) and pRb underexpression (score 0-2), possibly allows a better definition of abnormalities of p53 and pRb expression, thus providing more rigor in examining the correlation between these abnormalities and clinical outcome.…”

Expressão imuno-histoquímica e valor prognóstico da proteína p53 no carcinoma de vesícula biliar: estudo de 60 casos

“…Desde a primeira publicação realizada por Kamel et al (16) em 1993 para avaliar imuno-histoquimicamente a presença de expressão da proteína p53 no CaVB, poucas publicações (1,8,9,13,16,18,20,25,28,29,36,39,40,42) têm sido feitas, com achados bastante variáveis de positividade (entre 36,9% e 95%) e conflitantes em relação à associação dessa mutação com o prognóstico dos portadores dessa neoplasia.…”