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Hwang, Choi, and Park: Significance of Expression of Cell Cycle Related Proteins and Apoptosis Related Proteins in Follicular Adenoma and Follicular Carcinoma of Thyroid
Original Article
Journal of the Korean Surgical Society

Journal of the Korean Surgical Society 2009; 76(1): 7-14.

Published online: 31 January 2009

DOI: https://doi.org/10.4174/jkss.2009.76.1.7

Significance of Expression of Cell Cycle Related Proteins and Apoptosis Related Proteins in Follicular Adenoma and Follicular Carcinoma of Thyroid

Jun Young Hwang, M.D., Yoo Shin Choi, M.D., Sung Jun Park, M.D.

Department of Surgery, Chung-Ang University School of Medicine, Seoul, Korea.

ushinchoi@hotmail.com

Received 17 June 2008       Accepted 27 August 2008

Copyright © 2009 The Korean Surgical Society

Abstract

Purpose

To explore the role of cell cycle regulators and apoptosis regulators in carcinogenesis of thyroid, the expression of cell cycle related proteins (cyclin D1, Ki-67) and apoptosis related proteins (survivin, caspase 3, bcl-2, p53) were investigated in follicular adenoma and follicular carcinoma of thyroid.

Methods

The following formalin-fixed paraffin embedded surgical specimens were immunohistochemically stained by avidin-biotin complex method for cyclin D1, Ki-67, survivin, caspase 3, bcl-2, p53; 15 cases of follicular adenoma (FA), 31 cases of minimally invasive follicular carcinoma (MIFC) and 12 cases of widely invasive follicular carcinoma (WIFC).

Results

The overexpression of six gene products in follicular neoplasms of thyroid was noted in varying frequency. Among them, increased Ki-67, caspase 3 index and overexpression of bcl-2 were noted in statistically significant, widely invasive follicular carcinoma than that of follicular adenoma and minimally invasive follicular carcinoma.

Conclusion

These results suggest that the overexpression of Ki-67, caspase 3, bcl-2 appear to play an important role during follicular carcinogenesis of thyroid. In addition, the overexpression of these proteins is related to the differentiation of MIFC and WIFC. However, further molecular genetic studies are required to determine the interrelationships between the expression of cell cycle related proteins and apoptosis related proteins.

Keywords: Cell cycle related proteins, Apoptosis related proteins, Follicular adenoma (FA), Minimally invasive follicular carcinoma (MIFC), Widely invasive follicular carcinoma (WIFC)

Figures and Tables

Fig. 1
Hematoxylin and eosin staining. (A) Thyroid follicular adenoma shows microfollicle, prominent nuclei, intact capsule (H&E stain, ×100). (B) Thyroid minimally invasive follicular carcinoma shows mushroom pattern capsular invasion (H&E stain, ×100). (C) Thyroid widely invasive follicular carcinoma shows destructed capsule, aberrant cellular invasion (H&E stain, ×200).
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Fig. 2
Immunohistochemical staining. (A) Cyclin D1 in WIFC (IHC stain, ×200), (B) Ki-67 in WIFC (IHC stain, ×400), (C) Survivin in WIFC (IHC stain, ×200), (D) Caspase 3 in WIFC (IHC stain, ×400), (E) Bcl-2 in normal thyroid (A) and MIFC (B) (IHC stain, ×200), (F) p53 in WIFC (IHC stain, ×200).
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Fig. 3
Proportion of tumors expressing cyclin D1 according to histologic type.
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Fig. 4
Proportion of tumors expressing survivin according to histologic type.
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Fig. 5
Proportion of tumors expressing bcl-2 according to histologic type.
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Fig. 6
Proportion of tumors expressing p53 according to histologic type.
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Table 1
The expression of Ki-67 and caspase 3
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*FA = follicular adenoma; †MIFC = minimally invasive follicular carcinoma; ‡WIFC = widely invasive follicular carcinoma; §SD = standard deviation.

Table 2
Difference of expression of Ki-67 and caspase 3
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*FA = follicular adenoma; †MIFC = minimally invasive follicular carcinoma; ‡WIFC = widely invasive follicular carcinoma.

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