Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression Journal Article


Authors: Saltman, B.; Singh, B.; Hedvat, C. V.; Wreesmann, V. B.; Ghossein, R.
Article Title: Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression
Abstract: Background: Genetic screening studies suggest that genetic changes underlie progression from well differentiated to anaplastic thyroid cancers. The aim of this study is to determine to what extent cell cycle/apoptosis regulators contribute to cancer progression. Methods: Tissue microarrarys (TMAs) were constructed from well-differentiated papillary thyroid carcinoma (WDPTC; n = 41), poorly differentiated thyroid carcinoma (PDTC; n = 43), and anaplastic thyroid carcinoma (ATC; n = 22). TMAs were immunostained for 7 different cell cycle/apoptosis-related genes (p53, Ki-67, bcl-2, mdm-2, cyclin D1, p21, and p27). Results: p53 (0%, 12%, 32%) and Ki-67 (5%, 49%, 82%) were expressed with increasing frequency, and bcl-2 (68%, 42%, 0%) and p21 (40%, 7%, 0%) with decreasing frequency in WDPTC to PDTC and ATC, respectively (P < .001). Interestingly, mdm-2 (54%, 5%, 0%) showed decreased expression along the progression axis (P < .001). p27 and cyclin D1 were expressed in <15% of cases, with a trend toward decreasing expression from WDPTC to PDTC to ATC. Conclusions: These data confirm the presence of increasing genetic complexity with progressive dedifferentiation in thyroid cancer, with aberrant tumor suppressor activity and increased proliferative activity being most prevalent in ATC. The data also confirm the intermediate position of PDTC in the classification scheme of thyroid carcinomas. © 2006 Mosby, Inc. All rights reserved.
Keywords: immunohistochemistry; controlled study; human tissue; protein expression; human cell; histopathology; cancer growth; ki 67 antigen; ki-67 antigen; cell cycle; protein bcl 2; apoptosis; gene expression; carcinoma, papillary; tumor markers, biological; protein p53; gene expression regulation, neoplastic; microarray analysis; disease progression; protein p27; carcinoma; predictive value of tests; tumor suppressor protein p53; thyroid carcinoma; thyroid neoplasms; tissue microarray; cyclin-dependent kinase inhibitor p21; papillary carcinoma; cyclin d1; protein p21; proto-oncogene proteins c-bcl-2; anaplastic carcinoma; protein mdm2; proto-oncogene proteins c-mdm2; proliferating cell nuclear antigen; frequency analysis; genes, neoplasm
Journal Title: Surgery
Volume: 140
Issue: 6
ISSN: 0039-6060
Publisher: Elsevier Inc.  
Date Published: 2006-12-01
Start Page: 899
End Page: 906
Language: English
DOI: 10.1016/j.surg.2006.07.027
PUBMED: 17188136
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 27" - "Export Date: 4 June 2012" - "CODEN: SURGA" - "Source: Scopus"
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  1. Ronald A Ghossein
    482 Ghossein
  2. Cyrus Hedvat
    126 Hedvat
  3. Bhuvanesh Singh
    242 Singh