Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression.
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.
Saltman
Benjamin
B
Department of Otolaryngology, Columbia University College of Physicians and Surgeons, New York, NY 10021, USA.
Singh
Bhuvanesh
B
Hedvat
Cyrus V
CV
Wreesmann
Volkert B
VB
Ghossein
Ronald
R
D017209:Apoptosis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C413374:p27 antigen; D019938:Cyclin D1; D051736:Proto-Oncogene Proteins c-mdm2