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From the Clinical Cancer Genetics and Human Cancer
Genetics Programs,*
Ohio State University Comprehensive
Cancer Center, Columbus, Ohio; the Department of
Pathology,
University of Zürich,
Zürich, Switzerland; the Charles A. Dana Human Cancer Genetics
Unit,
Dana-Farber Cancer Institute, Boston,
Massachusetts; the Massachusetts Institute of
Technology,§
Boston, Massachusetts; the
Departments of Pathology and Surgery,¶
Martin-Luther-University of Halle-Wittenberg, Halle/Saale, Germany; the
Kolling Institute for Medical Research and Department of
Surgery,||
Royal North Shore Hospital, University of
Sydney, St. Leonards, New South Wales, Australia; the Department of
Pathology,**
Brigham and Women’s Hospital and
Harvard Medical School, Boston, Massachusetts; and the Cancer Research
Campaign Human Cancer Genetics Research
Group,
University of Cambridge,
Cambridge, United Kingdom
Germline mutations in PTEN (MMAC1/TEP1) are found in patients with Cowden syndrome, a familial cancer syndrome which is characterized by a high risk of breast and thyroid neoplasia. Although somatic intragenic PTEN mutations have rarely been found in benign and malignant sporadic thyroid tumors, loss of heterozygosity (LOH) has been reported in up to one fourth of follicular thyroid adenomas (FAs) and carcinomas. In this study, we examined PTEN expression in 139 sporadic nonmedullary thyroid tumors (55 FA, 27 follicular thyroid carcinomas, 35 papillary thyroid carcinomas, and 22 undifferentiated thyroid carcinomas) using immunohistochemistry and correlated this to the results of LOH studies. Normal follicular thyroid cells showed a strong to moderate nuclear or nuclear membrane signal although the cytoplasmic staining was less strong. In FAs the neoplastic nuclei had less intense PTEN staining, although the cytoplasmic PTEN-staining intensity did not differ significantly from that observed in normal follicular cells. In thyroid carcinomas as a group, nuclear PTEN immunostaining was mostly weak in comparison with normal thyroid follicular cells and FAs. The cytoplasmic staining was more intense than the nuclear staining in 35 to 49% of carcinomas, depending on the histological type. Among 81 informative tumors assessed for LOH, there seemed to be an associative trend between decreased nuclear and cytoplasmic staining and 10q23 LOH (P = 0.003, P = 0.008, respectively). These data support a role for PTEN in the pathogenesis of follicular thyroid tumors.
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Z. Yu, N. Fotouhi-Ardakani, L. Wu, M. Maoui, S. Wang, D. Banville, and S.-H. Shen PTEN Associates with the Vault Particles in HeLa Cells J. Biol. Chem., October 18, 2002; 277(43): 40247 - 40252. [Abstract] [Full Text] [PDF]
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X.-P. Zhou, A. Loukola, R. Salovaara, M. Nystrom-Lahti, P. Peltomaki, A. de la Chapelle, L. A. Aaltonen, and C. Eng PTEN Mutational Spectra, Expression Levels, and Subcellular Localization in Microsatellite Stable and Unstable Colorectal Cancers Am. J. Pathol., August 1, 2002; 161(2): 439 - 447. [Abstract] [Full Text] [PDF]
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M. Fernandez and C. Eng The Expanding Role of PTEN in Neoplasia: A Molecule for All Seasons? : Commentary re: M. A. Davies, et al., Adenoviral-mediated Expression of MMAC/PTEN Inhibits Proliferation and Metastasis of Human Prostate Cancer Cells. Clin. Cancer Res., 8: 1904-1914, 2002. Clin. Cancer Res., June 1, 2002; 8(6): 1695 - 1698. [Abstract] [Full Text] [PDF]
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W. Liu, S. L. Asa, I. G. Fantus, P. G. Walfish, and S. Ezzat Vitamin D Arrests Thyroid Carcinoma Cell Growth and Induces p27 Dephosphorylation and Accumulation through PTEN/Akt-Dependent and -Independent Pathways Am. J. Pathol., February 1, 2002; 160(2): 511 - 519. [Abstract] [Full Text] [PDF]
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G. L. Mutter PTEN, a Protean Tumor Suppressor Am. J. Pathol., June 1, 2001; 158(6): 1895 - 1898. [Full Text] [PDF]
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K. Kurose, X.-P. Zhou, T. Araki, S. A. Cannistra, E. R. Maher, and C. Eng Frequent Loss of PTEN Expression Is Linked to Elevated Phosphorylated Akt Levels, but Not Associated with p27 and Cyclin D1 Expression, in Primary Epithelial Ovarian Carcinomas Am. J. Pathol., June 1, 2001; 158(6): 2097 - 2106. [Abstract] [Full Text] [PDF]
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L.-P. Weng, O. Gimm, J. B. Kum, W. M. Smith, X.-P. Zhou, D. Wynford-Thomas, G. Leone, and C. Eng Transient ectopic expression of PTEN in thyroid cancer cell lines induces cell cycle arrest and cell type-dependent cell death Hum. Mol. Genet., February 1, 2001; 10(3): 251 - 258. [Abstract] [Full Text] [PDF]
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O. Gimm, M. Armanios, H. Dziema, H. P. H. Neumann, and C. Eng Somatic and Occult Germ-line Mutations in SDHD, a Mitochondrial Complex II Gene, in Nonfamilial Pheochromocytoma Cancer Res., December 1, 2000; 60(24): 6822 - 6825. [Abstract] [Full Text]
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A. Perren, P. Komminoth, P. Saremaslani, C. Matter, S. Feurer, J. A. Lees, P. U. Heitz, and C. Eng Mutation and Expression Analyses Reveal Differential Subcellular Compartmentalization of PTEN in Endocrine Pancreatic Tumors Compared to Normal Islet Cells Am. J. Pathol., October 1, 2000; 157(4): 1097 - 1103. [Abstract] [Full Text] [PDF]
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X.-P. Zhou, O. Gimm, H. Hampel, T. Niemann, M. J. Walker, and C. Eng Epigenetic PTEN Silencing in Malignant Melanomas without PTEN Mutation Am. J. Pathol., October 1, 2000; 157(4): 1123 - 1128. [Abstract] [Full Text] [PDF]
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O. Gimm, T. Attie-Bitach, J. A. Lees, M. Vekemans, and C. Eng Expression of the PTEN tumour suppressor protein during human development Hum. Mol. Genet., July 1, 2000; 9(11): 1633 - 1639. [Abstract] [Full Text] [PDF]
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J. Torres and R. Pulido The Tumor Suppressor PTEN Is Phosphorylated by the Protein Kinase CK2 at Its C Terminus. IMPLICATIONS FOR PTEN STABILITY TO PROTEASOME-MEDIATED DEGRADATION J. Biol. Chem., January 5, 2001; 276(2): 993 - 998. [Abstract] [Full Text] [PDF]
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