A comparison between p53 accumulation determined by immunohistochemistry and<i>TP53</i>mutations as prognostic variables in tumours from breast cancer patients

Alsner, Jan; Jensen, Viggo A.; Kyndi, Marianne; Offersen, Birgitte Vrou; Vu, Phuong; Børresen-Dale, Anne Lise; Overgaard, Jens

doi:10.1080/02841860802047411

Cited by 89 publications

(80 citation statements)

References 17 publications

(31 reference statements)

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“…Immunolabeling for p53 was interpreted as positive and predictive of TP53 mutations if 475% tumors cell show strong positive staining. 7 Expression of E-cadherin was considered intact (normal) when 450% of the neoplastic cells showed membranous labeling. E-cadherin labeling was considered reduced when 10-50% of the cells labeled and, and negative when o10% of the neoplastic cells labeled.…”

Section: Immunohistochemical Stainsmentioning

confidence: 99%

Adenosquamous carcinoma of the pancreas harbors KRAS2, DPC4 and TP53 molecular alterations similar to pancreatic ductal adenocarcinoma

et al. 2009

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Adenosquamous carcinoma of the pancreas is one of the most aggressive forms of pancreatic cancer. Molecular characterizations of this rare tumor subtype are sparse. Understanding the common molecular and pathologic features of pancreatic adenosquamous carcinomas could provide critical information for identifying therapeutic targets. Herein, we analyzed the pathologic and molecular features of our series of eight pancreatic adenosquamous carcinomas. We found KRAS2 gene mutations at codon 12 in all eight cases. All the cases showed loss of p16 protein. In three of these cases the loss was attributed to an exon 2 homozygous deletion in the p16/CDKN2a gene. The majority of the cases had loss of Dpc4 protein and strong nuclear p53 positivity, similar to the molecular signature found in pancreatic ductal adenocarcinoma. We found that E-cadherin was either lost or reduced in all cases and that epidermal growth factor receptor was overexpressed in all cases. The squamous component was positive for p63 staining and thus p63 labeling was helpful in identifying squamous differentiation in adenosquamous carcinomas with an acantholytic growth pattern. In summary, although pancreatic adenosquamous carcinoma and ductal adenocarcinoma have overlapping pathologic and molecular characteristics, there are distinct differences that may be helpful in diagnostic and therapeutic strategies.

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Section: Immunohistochemical Stainsmentioning

confidence: 99%

Adenosquamous carcinoma of the pancreas harbors KRAS2, DPC4 and TP53 molecular alterations similar to pancreatic ductal adenocarcinoma

et al. 2009

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“…They are 3-septate, fusiform, cylindrical, often moderately curved, with an indistinctly pedicellate foot cell and a short blunt apical cell, (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42) 毺m 暳 4-6 毺m). Microconidia are usually abundant, cylindrical to oval, oneto two-celled and formed from long lateral phialides, (8)(9)(10)(11)(12)(13)(14)(15)(16) 毺m 暳 2-4.5 毺m). Chlamydospores are hyaline, globose, smooth to rough-walled, borne singly on short lateral hyphal branches.…”

Section: Resultsmentioning

confidence: 99%

“…The level of expression of mRNA after treatment with the cell free crude extract from the two isolates was then analyzed by using RT-PCR for the P53 gene. Tumor protein P53 is a tumor suppressor protein that in humans is encoded by the TP53 gene [14][15][16][17] . p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer.…”

Section: A R T I C L E I N F O Abstractmentioning

confidence: 99%

Molecular analysis and anticancer properties of two identified isolates, Fusarium solani and Emericella nidulans isolated from Wady El–Natron soil in Egypt against Caco–2 (ATCC) cell line

Mohamed

2012

Asian Pacific Journal of Tropical Biomedicine

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“…Although the consensus in the p53 field is that low TP53 expression is associated with wild-type TP53, [47][48][49][50] it is important to indicate that DNA of all tumor samples needs to be sequenced in order to correlate the presence of wild-type TP53 with PTPN6 and NTRK1-pY674/pY675 in our data set.…”

Section: Discussionmentioning

confidence: 99%

“…[47][48][49][50] Thus, in order to determine whether NTRK1-pY674/pY675 together with undetectable or low levels of PTPN6 and TP53 expression are associated with improved disease-free survival, tumors showing together this NTRK1-pY674/pY675, PTPN6, and TP53 expression pattern were analyzed as they meet the conditions described by Montano. 28 Tumors meeting these conditions were denoted as 1 and others were denoted as 0.…”

Section: Clinicopathological Parameters and Patient Outcomementioning

confidence: 99%

Phosphorylation of NTRK1 at Y674/Y675 induced by TP53-dependent repression of PTPN6 expression: A potential novel prognostic marker for breast cancer

Youssef¹,

Gillett

Agbaje

et al. 2014

Modern Pathology

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We have identified a ligand-independent mechanism whereby the tumor suppressor, TP53, induces nerve growth factor receptor, NTRK1, phosphorylation at Y674/Y675 (NTRK1-pY674/pY675), via the repression of the NTRK1-phosphatase, PTPN6. This results in suppression of breast cancer cell proliferation. In this investigation, we aimed to establish whether perturbation of the wild-type TP53-NTRK1-pY674/pY675-PTPN6 pathway has an impact on disease-free survival of breast cancer patients without neo-adjuvant treatment. A total of 308 tumor samples were stained for NTRK1, NTRK1-pY674/pY675, PTPN6, and TP53 expression. Association between expression levels and disease-free survival was determined by the univariate/multivariate and Kaplan-Meir methods of analysis. DNA from tumors was sequenced to identify mutant or wild-type TP53. Tumors expressing NTRK1-pY674/pY675 but with undetectable or low levels of PTPN6 and TP53 were associated with prolonged 5, 10, and 15 years' disease-free survival by 48%, 36%, and 37%, respectively, in the multivariate analysis (Po0.05). A similar result was observed in tumors expressing wild-type TP53, NTRK1-pY674/pY675, and low or undetectable levels of PTPN6. Given that estrogen receptor-positive breast cancers encode wild-type TP53, we analyzed this expression pattern in these tumors. Multivariate analysis showed that it was significantly and independently predictive of prolonged survival by 66%, 70%, and 84%, respectively, (Po0.05). The Kaplan-Meir method demonstrated that NTRK1-pY674/pY675 together with undetectable or low levels of PTPN6 correlated with 59% probability of disease-free survival (median survival 15 years), compared with 7% probability of disease-free survival (median survival 4.5 years) when absent. In luminal A tumors, the presence of this pattern was estimated to have a 61% probability of disease-free survival (median survival 15 years), compared with 6% probability of disease-free survival (median survival 3 years) when it was absent. These results strongly suggest that expression of NTRK1-pY674/pY675 together with wild-type TP53 and low levels of PTPN6 expression are predictors of improved disease-free survival and that they could be useful biomarkers to predict clinical outcome. Breast cancer is a leading cause of early mortality among women. 1 The incidence varies worldwide, with developed countries having higher rates than developing countries. 1,2 Although the rate of breast cancer has continued to increase, 3 mortality rates have decreased, partly due to the enhanced use of diagnostic and screening techniques. 4,5

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A comparison between p53 accumulation determined by immunohistochemistry andTP53mutations as prognostic variables in tumours from breast cancer patients

Abstract: A comparison between p53 accumulation determined by immunohistochemistry and TP53 mutations as prognostic variables in tumours from breast cancer patients, Acta Oncologica, 47:4, 600-607,

Cited by 89 publications

References 17 publications

Adenosquamous carcinoma of the pancreas harbors KRAS2, DPC4 and TP53 molecular alterations similar to pancreatic ductal adenocarcinoma

Adenosquamous carcinoma of the pancreas harbors KRAS2, DPC4 and TP53 molecular alterations similar to pancreatic ductal adenocarcinoma

Molecular analysis and anticancer properties of two identified isolates, Fusarium solani and Emericella nidulans isolated from Wady El–Natron soil in Egypt against Caco–2 (ATCC) cell line

Phosphorylation of NTRK1 at Y674/Y675 induced by TP53-dependent repression of PTPN6 expression: A potential novel prognostic marker for breast cancer

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