J Korean Soc Endocrinol.  2005 Aug;20(4):362-374. 10.3803/jkes.2005.20.4.362.

Chromosomal Analysis of Anaplastic Thyroid Carcinomas by Comparative Genomic Hybridization

• Kim MK
• Lee CH
• Song JM
• Gong KY
• Kim YK

• KMID: 2100467
• DOI: http://doi.org/10.3803/jkes.2005.20.4.362

Abstract

BACKGROUND: Compared with common well-differentiated thyroid carcinomas, the genetic alterations underlying the development and progression of anaplastic thyroid carcinomas(ATC) are still uncharacterized. Comparative genomic hybridization(CGH) is a cytogenetic technique that can identify gains and losses in the DNA sequence copy number in tumors.
METHODS
The authors studied the changes in the DNA copy number due to CGH in paraffin-embedded tissue blocks of 17 ATC cases, and tried to ascertain whether the genomic changes correlate with the clinicopathological parameters including patients' age, sex, primary tumor size, lymphovascular invasion, extrathyroid extension, regional node metastasis and immunohistochemical expression of cyclin D1.
RESULTS
Fourteen of the 17 samples(82.4%) showed chromosomal changes, with a mean number of gains or losses per carcinoma of 3.6(range 2~6; 30 gains and 21 losses). The most frequently detected imbalance was the gain of chromosome 1q, which was seen in 35.7% of cases, particularly commonly in ATC associated with a papillary thyroid carcinoma. Other commonly occurring gains were present in 11q13 and 19(28.6%, respectively). Genomic amplification was detected in all four cases showing the 11q13 gain. Genomic losses were commonly noted in 3q, 6q, 18q andchi(21.4%, respectively). When numerical CGH alterations were compared to the clinicopathological parameters, there were no significant correlations(P>0.05). Cyclin D1 expression was noted in sixteen of the 17 cases(94.1%), but the extent of cyclin D1 expression was not correlated with the numerical CGH alterations(P>0.05).
CONCLUSION
Taken together, the aberrations of 1q, 3q, 6q, 11q13 and 18q are relatively common in ATC, and may play an important role it developement. These findings should lead to the characterization of tumor suppressor genes and oncogenes that are potentially involved in the carcinogenesis of ATC. The amplification of 11q13 is characteristically found, but cyclin D1 in this region may be innocent of the aggressiveness of these carcinomas.

MeSH Terms

Base Sequence
Carcinogenesis
Comparative Genomic Hybridization*
Cyclin D1
Cytogenetic Analysis
DNA
Genes, Tumor Suppressor
Neoplasm Metastasis
Oncogenes
Thyroid Gland*
Thyroid Neoplasms*
Cyclin D1
DNA

Figure

• 

  Fig. 1 Light microscopic findings of anaplastic thyroid carcinoma. (A) Infiltrative sheets composed of spindle and epidermoid anaplastic tumor cells are noted. A few residual thyroid follicles are present on the left lower (×200). (B) Anaplastic carcinoma, being reminiscent of squamous cell carcinoma, is associated with papillary thyroid carcinoma on the left lower (×100)

• 

  Fig. 2 Summary of genetic imbalances detected by CGH in 14 cases of anaplastic thyroid carcinoma. The gains in green bricks are shown on the right side of chromosomes, and the losses in red bricks shown on the left. The length of each brick represents a gained or lost region in a single tumor

• 

  Fig. 3 Representative CGH image of anaplastic thyroid carcinoma case 12. Fluorescence ratio image shows tumor DNA and normal DNA hybridized onto normal metaphase chromosome. Green regions represent gains and red regions display losses. Uninvolved regions appear yellow

• 

  Fig. 4 Partial fluorescence ratio profile of chromosomes (CHRs) 1 and 11 from anaplastic thyroid carcinoma case 12. CGH profiles display the gains of DNA copy number at 1q and 11q13 regions. The 11q13 region shows amplification

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  Fig. 5 Immunohistochemical staining for cyclin D1. (A) The nuclei of anaplastic thyroid carcinoma focally show cyclin D1 positivity in about less than 25% of tumor area (×200). (B) The nuclei of anaplastic carcinoma show diffuse cyclin D1 positive reaction in about more than 50% of tumor area (×200)

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