p53 and c‐erbB‐2 protein expression in adenocarcinomas and epithelial dysplasias of the gall bladder

Abstract

In this study we investigated immunohistochemically the expression of p53 and c-erbB-2 proteins in 30 gall bladder adenocarcinomas, one carcinoma in situ, eight gall bladder epithelial dysplasias, and four cases of chronic cholecystitis. p53 expression could be found in 14 (47 per cent) adenocarcinomas and in two out of eight epithelial dysplasias. There were significantly more p53-positive grade II-III tumours than grade I tumours (P = 0.032 according to Fisher's exact probability test). c-erbB-2 expression was found in three (10 per cent) adenocarcinomas, but all dysplasias were c-erbB-2-negative. All three c-erbB-2-positive cases were also p53-positive. The results indicate that p53 mutations and c-erbB-2 gene alterations play a role in the neoplastic transformation of gall bladder epithelial cells. Co-expression of p53 and c-erbB-2 suggests that alterations of these genes might act in concert in the neoplastic transformation. The occurrence of p53 expression in gall bladder dysplasias suggests that p53 mutations could be an early event in the evolution of some gall bladder carcinomas, as has been suggested for some other types of tumours, such as lung squamous cell carcinomas.

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.…”

“…5,6 Activation of oncogene c-erbB-2 has also been shown in GBCs; however, its clinical significance has not been clarified. 1 It is important to identify alterations that correlate with tumor progression and clinical outcome in GBCs.…”

“…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.…”

E1A, E1B double-restricted replicative adenovirus at low dose greatly augments tumor-specific suicide gene therapy for gallbladder cancer

“…In addition, the combination exhibited enhanced safety, in terms of its effects on normal cells, as compared to the combination of AxCAHSVtk and AxdAdB-3. These results suggests the efficacy of this approach especially for the treatment of GBC, which is characterized both by high rates of abnormalities in p53 and Rb pathways [34][35][36][37][38] and by a high incidence of CEA production. 39 …”

Telomere length variation in biliary tract metaplasia, dysplasia, and carcinoma

“…Additionally, metaplastic changes have been implicated as an even earlier potential precursor in gallbladder carcinoma. 4,5 Risk factors for the development of biliary tract carcinoma include race (increased risk in native and Hispanic Americans), cholelithiasis, abnormal junction of the pancreatic and biliary duct for gallbladder carcinoma, and primary sclerosing cholangitis and choledochal cyst for carcinoma of the extrahepatic bile ducts. The frequent advanced nature of disease on presentation, as well as limited knowledge of causative molecular factors underlying biliary tract carcinoma, has limited the therapeutic options for patients with this cancer.…”