p53 Mutations are common in pancreatic cancer and are absent in chronic pancreatitis

Casey, Graham; Yamanaka, Yoichiro; Frieß, Helmut; Kobrin, Michael S.; Lopez, Martha E.; Büchler, Markus W.; Beger, Hans G.; Korc, Murray

doi:10.1016/0304-3835(93)90168-9

Cited by 159 publications

(87 citation statements)

References 27 publications

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“…The parental cell line for mutant AP14, HT1080, is a human ®brosarcoma containing high levels of p53. Transient transfection assays for the induction of luciferase from a p53-dependent promoter, Western analysis for induction of p53 protein and direct sequencing of the coding region of p53 (our data not shown), using the primers developed by Casey et al (1993), have revealed that the p53 protein in HT1080 cells is wild-type, inducible, and fully functional as a transcriptional activator. HT1080 cells do not undergo apoptosis or cell-cycle arrest when wild-type p53 is expressed at an even higher level from a constitutive promoter (our data not shown).…”

Section: Cell Lines and Culture Conditionsmentioning

confidence: 76%

Regulation of p53 expression by the RAS-MAP kinase pathway

et al. 2001

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Activation of MAP kinase leads to the activation of p53-dependent pathways, and vice-versa. Although the amount of p53 protein increases in response to MAP kinase-dependent signaling, the basis of this increase is not yet fully understood. We have isolated the mutant cell line AP14, defective in p53 expression, from human HT1080 ®brosarcoma cells, which have an activated ras allele. The expression of p53 mRNA and protein is *10-fold lower in AP14 cells than in the parental cells. The high constitutive phosphorylation and activities of the MAP kinases ERK1 and ERK2 in HT1080 cells are greatly reduced in AP14 cells, although the levels of these proteins are unchanged, suggesting that the defect in the mutant cells a ects the steady-state phosphorylation of ERK1 and ERK2. Overexpression of ERK2 in AP14 cells restored both MAP kinase activity and p53 expression, and incubation of the mutant cells with the phosphatase inhibitor orthovanadate resulted in strong coordinate elevation of MAP kinase activity and p53 expression. The levels of expression of the p53-regulated gene p21 parallel those of p53 throughout, showing that basal p21 expression depends on p53. The levels of p53 mRNA increased by 5 ± 8-fold when activated ras was introduced into wild-type cells, and the levels of the p53 and p21 proteins decreased substantially in wild-type cells treated with the MEK inhibitor U0216. We conclude that MAP kinase-dependent pathways help to regulate p53 levels by regulating the expression of p53 mRNA. Oncogene (2001) 20, 2527 ± 2536.

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Section: Cell Lines and Culture Conditionsmentioning

confidence: 76%

Regulation of p53 expression by the RAS-MAP kinase pathway

et al. 2001

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“…It was reported that p53 mutations were common in pancreatic cancers. 30,31 Hence, pancreatic cancers are proper indications for Ad-PUMA treatment. In vivo experiments also confirmed the synergistic effects of Ad-PUMA and chemical drugs on pancreatic cancer cell model.…”

Section: Discussionmentioning

confidence: 99%

A feasibility study on gene therapy of pancreatic carcinoma with Ad-PUMA

Wang¹,

Pei²,

Luan³

et al. 2012

Cancer Biology & Therapy

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“…It is inactivated largely via mutation, usually resulting in nuclear accumulation and positive IH stain [23][24][25] . The p53 abnormality is detected in 50% to 90% of pancreatic adenocarcinomas [23][24][25][26][27][28][29][30][31] , and in their precursor, PanIN, the positive stain ing is directly correlated to the grade [17,[29][30][31] . Our findings agree with previous studies on EUS-FNA of pancreas, which showed that the addition of p53 IH or DNA analysis resulted in a modest sensitivity gain [12][13][14] .…”

Section: Discussionmentioning

confidence: 99%

Staining for p53 and Ki-67 increases the sensitivity of EUS-FNA to detect pancreatic malignancy

Jahng

Reicher²,

Chung³

et al. 2010

WJGE

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AIM:To investigate whether tumor marker staining can improve the sensitivity of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to diagnose pancreatic malignancy. METHODS:Patients who underwent EUS-FNA were retrospectively identified. Each EUS-FNA specimen was evaluated by routine cytology and stained for tumor markers p53, Ki-67, carcinoembryonic antigen (CEA) and CA19-9. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (PLR and NLR) were calculated in order to evaluate the performance of each test to detect malignancy. RESULTS:Sixty-one specimens had complete sets of stains, yielding 49 and 12 specimens from pancreatic adenocarcinomas and benign pancreatic lesions due to pancreatitis, respectively. Cytology alone had sensitivity and specificity of 41% and 100% to detect malignancy, respectively. In 46% of the specimens, routine cytology alone was deemed indeterminate. The addition of either p53 or Ki-67 increased the sensitivity to 51% and 53%, respectively, with perfect specificity, PPV and PLR (100%, 100% and infinite). Both stains in combination increased the sensitivity to 57%. While additional staining with CEA and CA19-9 further increased the sensitivity to 86%, the specificity, PPV and PLR were significantly reduced (at minimum 42%, 84% and 1, respectively). Markers in all combinations performed poorly as a negative test (NPV 26% to 47%, and NLR 0.27 and 0.70). CONCLUSION: Immunohistochemical staining for p53and Ki-67 can improve the sensitivity of EUS-FNA to diagnose pancreatic adenocarcinoma.

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p53 Mutations are common in pancreatic cancer and are absent in chronic pancreatitis

Cited by 159 publications

References 27 publications

Regulation of p53 expression by the RAS-MAP kinase pathway

Regulation of p53 expression by the RAS-MAP kinase pathway

A feasibility study on gene therapy of pancreatic carcinoma with Ad-PUMA

Staining for p53 and Ki-67 increases the sensitivity of EUS-FNA to detect pancreatic malignancy

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