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Kim, Lee, Song, Gong, and Kim: Chromosomal Analysis of Anaplastic Thyroid Carcinomas by Comparative Genomic Hybridization
Original Article
Journal of Korean Society of Endocrinology

Journal of Korean Society of Endocrinology 2005; 20(4): 362-374.

Published online: 31 August 2005

DOI: https://doi.org/10.3803/jkes.2005.20.4.362

Chromosomal Analysis of Anaplastic Thyroid Carcinomas by Comparative Genomic Hybridization

Mi Kyoung Kim1, 2, Chang Hun Lee3, Jin Mi Song3, Kyung Yub Gong4, Yong Ki Kim2

1Department of Internal Medicine, Wallace Memorial Baptist Hospital, Korea.

2Department of Internal Medicine, School of Medicine, Pusan National university, Busan, Korea.

3Department of Pathology, School of Medicine, Pusan National university, Busan, Korea.

4Department of Pathology University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Received 28 April 2005       Accepted 8 July 2005

Copyright © 2005 Korean Endocrine Society

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 and×(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.

Keywords: Anaplastic Thyroid Carcinoma, Comparative Genomic Hybridization, Cyclin D1

Figures and Tables

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)
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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
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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
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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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Table 1
Clinicopathologic Findings in 19 Anaplastic Thyroid Carcinomas
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F, female; M, male; WTC, well differentiated thyroid carcinoma; PTC, papillary thyroid carcinoma; ETE, extrathyroid extension; LVI, lymphovascular invasion; LNM, regional lymph node metastasis; Unk, unknown.

Table 2
Results of Comparative Genomic Hybridization Study in 17 Anaplastic Thyroid Carcinomas
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*in bold-regions : high amplifications were observed.

Table 3
Relationship between cyclin D1 expression and clinicopathologic
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㐸 : 1+, cyclin D1 positivity in less than 25 % of tumor area; 2~3+, cyclin D1 positivity in more than 25% of tumor area.

LVI, lymphovascular invasion; LNM, regional lymph node metastasis.

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