Journal ArticleDOI
Clinicopathological significance of nuclear PTEN expression in colorectal adenocarcinoma.
Kiseok Jang,Young Soo Song,Si-Hyong Jang,Kyueng-Whan Min,Woong Na,Se Min Jang,Young Jin Jun,Kang Hong Lee,Dong Ho Choi,Seung Sam Paik +9 more
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TLDR
Jang K‐S, Song Y S,Jang S‐H, Min K‐W, Na W, Jang S M, Jun Y J, Lee K H, Choi D & Paik S S
(2010) Histopathology56, 229–239.Abstract:
Jang K-S, Song Y S, Jang S-H, Min K-W, Na W, Jang S M, Jun Y J, Lee K H, Choi D & Paik S S (2010) Histopathology56, 229–239
Clinicopathological significance of nuclear PTEN expression in colorectal adenocarcinoma
Aims: Tumour suppressor phosphatase and tensin homologue (PTEN) is an important negative regulator for the PIP3/Akt signalling pathway that promotes cell proliferation and inhibits apoptosis. Inactivation of PTEN by mutation, deletion and promoter hypermethylation has been demonstrated in a range of cancers. The aim was to investigate whether the loss of nuclear PTEN protein expression correlates with conventional clinicopathological parameters and patient survival.
Methods and results: Immunohistochemistry staining for PTEN was performed on a tissue microarray of 19 samples of normal colonic mucosa, 14 adenomatous polyps, 482 adenocarcinomas and 56 metastatic lymph nodes. All 19 normal colonic mucosa samples (100%) were positive and 12 (85.7%) out of 14 adenomatous polyps were positive for PTEN. However, only 241 (50.0%) of the 482 colorectal adenocarcinomas and 26 (46.4%) of the 56 metastatic lymph nodes were positive for PTEN. Loss of PTEN expression was related to defective mismatch repair protein expression and colonic localization rather than rectal localization. On univariate survival analysis, patients with PTEN− adenocarcinoma revealed a poor overall and disease-free survival (P = 0.030 and P = 0.046, respectively). On multivariate analysis, a significant difference was observed in patients with stage II cancer that was not observed in other stages.
Conclusions: Nuclear PTEN expression gradually decrease during the normal–adenoma–adenocarcinoma–metastasis sequence, which suggests an important role for PTEN in carcinogenesis. Moreover, loss of nuclear PTEN expression was a marker of poor clinical outcome in patients with stage II colorectal cancer.read more
Citations
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Journal ArticleDOI
PTEN loss increases PD-L1 protein expression and affects the correlation between PD-L1 expression and clinical parameters in colorectal cancer.
Minmin Song,De-Feng Chen,Biyan Lu,Chenliang Wang,Junxiao Zhang,Lanlan Huang,Xiaoyan Wang,Christine L. Timmons,Jun Hu,Bindong Liu,Xiaojian Wu,Lei Wang,Jianping Wang,Huanliang Liu +13 more
TL;DR: PD-L1 can be used to identify CRC patients with high risk of metastasis and poor prognosis and this clinical manifestation may be partly associated with PTEN expression.
Journal ArticleDOI
Mechanisms of PTEN loss in cancer: it’s all about diversity
TL;DR: The data relating to PTEN loss in seven common tumour types is reviewed and mechanisms of PTEN regulation, some of which appear to contribute to reduced PTEN protein levels in cancers are discussed.
Journal ArticleDOI
MicroRNA-32 (miR-32) regulates phosphatase and tensin homologue (PTEN) expression and promotes growth, migration, and invasion in colorectal carcinoma cells
Weiyun Wu,Jingfang Yang,Xiao Feng,Hao Wang,Shicai Ye,Pengchun Yang,Wenkai Tan,Guoli Wei,Yu Zhou +8 more
TL;DR: It is demonstrated that miR-32 was involved in tumorigenesis of CRC at least in part by suppression of PTEN, and PTEN was identified as the functional downstream target of mi R-32 by directly targeting the 3′-UTR ofPTEN.
Journal ArticleDOI
A Review of the Most Promising Biomarkers in Colorectal Cancer: One Step Closer to Targeted Therapy
TL;DR: An update of the most recent data on promising biological prognostic and/or predictive markers, including microsatellite instability, epidermal growth factor receptor, KRAS, BRAF, CpG island methylator phenotype, cytotoxic T lymphocytes, forkhead box P3-positive T cells, receptor for hyaluronic acid-mediated motility, phosphatase and tensin homolog, and T-cell originated protein kinase, in patients with CRC is provided.
Journal ArticleDOI
The prognostic role of KRAS , BRAF , PIK3CA and PTEN in colorectal cancer
Vincy Eklöf,Maria L. Wikberg,Sofia Edin,Anna M. Dahlin,Björn-Anders Jonsson,Åke Öberg,Jörgen Rutegård,Richard Palmqvist +7 more
TL;DR: The results suggest that establishment of molecular subgroups based on KRAS and BRAF mutation status is important and should be considered in future prognostic studies in CRC.
References
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Journal ArticleDOI
PTEN, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer
Jing Li,Clifford Yen,Danny Liaw,Katrina Podsypanina,Shikha Bose,Steven I. Wang,Janusz Puc,Christa Miliaresis,Linda Rodgers,Richard W. McCombie,Sandra H. Bigner,Beppino C. Giovanella,Michael Ittmann,B. Tycko,Hanina Hibshoosh,Michael Wigler,Ramon Parsons +16 more
TL;DR: The PTEN product has a protein tyrosine phosphatase domain and extensive homology to tensin, a protein that interacts with actin filaments at focal adhesions as discussed by the authors.
Journal ArticleDOI
The Tumor Suppressor, PTEN/MMAC1, Dephosphorylates the Lipid Second Messenger, Phosphatidylinositol 3,4,5-Trisphosphate
Tomohiko Maehama,Jack E. Dixon +1 more
TL;DR: It is demonstrated that overexpression of PTEN, a putative tumor suppressor, reduced insulin-induced PtdIns(3,4,5)P3 production in human 293 cells without effecting insulin- induced phosphoinositide 3-kinase activation.
Journal ArticleDOI
Negative Regulation of PKB/Akt-Dependent Cell Survival by the Tumor Suppressor PTEN
Vuk Stambolic,Vuk Stambolic,Akira Suzuki,Akira Suzuki,José Luis de la Pompa,José Luis de la Pompa,Christine Mirtsos,Christine Mirtsos,Takehiko Sasaki,Takehiko Sasaki,Jürgen Ruland,Jürgen Ruland,Josef M. Penninger,Josef M. Penninger,David P. Siderovski,David P. Siderovski,Tak W. Mak,Tak W. Mak +17 more
TL;DR: The results show that PTEN may exert its role as a tumor suppressor by negatively regulating the PI3'K/PKB/Akt signaling pathway.
Journal ArticleDOI
Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome
Danny Liaw,Deborah J. Marsh,Jing Li,Patricia L. M. Dahia,Steven I. Wang,Z. Zheng,Shikha Bose,K. M. Call,Hui C. Tsou,Monica Peacocke,Charis Eng,Ramon Parsons +11 more
TL;DR: Mutational analysis of PTEN in CD kindreds has identified germline mutations that are predicted to disrupt the protein tyrosine/dual-specificity phosphatase domain of this gene, and implies that PTEN may play a role in organizing the relationship of different cell types within an organ during development.
Journal ArticleDOI
Pten is essential for embryonic development and tumour suppression.
TL;DR: The notion that PTEN haploinsufficiency plays a causal role in CD, LDD and BZS pathogenesis is supported, and it is demonstrated that Pten is a tumour suppressor essential for embryonic development.
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