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Lee, Lee, Lee, Park, and Kim: Correlation between S100A4 and COX2 Overexpression and Invasiveness of Papillary Thyroid Carcinoma
Original Article

J Korean Endocr Soc 2008;23(3):186-192.

Published online: 10 January 2008

DOI: https://doi.org/10.3803/jkes.2008.23.3.186

Correlation between S100A4 and COX2 Overexpression and Invasiveness of Papillary Thyroid Carcinoma

Kyungji Lee, Youn Soo Lee, Kyo-Young Lee, Woo-Chan Park1, Young Sil Kim2

Department of Hospital Pathology, College of Medicine, The Catholic University of Korea

1Department of Surgery, College of Medicine, The Catholic University of Korea

2Department of Pathology, University of Jeju

Received 31 July 2007       Accepted 17 March 2008

Copyright © 2008 Korean Endocrine Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

Tumor cell invasion is characteristic of malignant neoplasms. S100A4, a member of a family of small calcium binding proteins, and COX2, seem to have a role in promoting progression and invasion of many human cancers. The clinical stage of a papillary thyroid carcinoma (PTC) depends on age, tumor size, and extrathyroidal extension. Extrathyroidal extension is correlated with the invasiveness of a tumor. However, there are no reliable prediction markers for invasiveness. We evaluated S100A4 and COX2 expression in PTCs to determine if expression correlates with invasiveness, and if expression of S100A4 and COX2 are useful as prediction markers.

Methods

The expression of S100A4 and COX2 were evaluated using immunohistochemical analysis in 35 PTC specimens.

Results

More intense staining in cells that invaded the front portion rather than the central portion of a PTC was indicative of increased expression of S100A4 and COX2. Therefore, cases were analyzed for extent of staining in tumor cells that invaded the front portion of a PTC. High expression group (higher expression than average expression rate) of S100A4 and COX2 were significantly correlated with extrathyroidal extension (P = 0.0094 and P = 0.0433, respectively). However, no other clinicopathological factors including age, lymph node involvement, and multiplicity were related to expression of S100A4 and COX2, as determined in this study.

Conclusion

Extrathyroidal extension of a PTC had an unfavorable effect on prognosis. S100A4 and COX2 expression were associated with extrathyroidal extension. These findings suggest that expression of S100A4 and COX2 could be prognostic markers for PTC.

Keywords: cyclooxygenase2, papillary thyroid carcinoma, S100A4

References

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Fig. 1.
S100A4 and COX2 immunostaining in papillary thyroid carcinoma. It is noted few positive cells in well defined mass (a, S100A4, X200) (c, COX2, X200). There are many strong cytoplasmic or nuclear positive cells in invading fronts (b, S100A4, X200) (d, COX2, X200).
jkes-23-186f1.tif
Table 1.
Summary of clinical data and pathological features
No Sex Age Size ET ext† LN meta‡ Multi§ pT stage % reactive COX2 cells II % reactive S100A4 cells II
1 F 42 1.5 Y N N pT3 35 30
2 F 66 1.0 N N N pT1 10 1
3 F 46 0.8 Y N N pT3 30 8
4 F 44 0.5 Y N N pT3 15 40
5 F 29 1.0 Y Y N pT3 10 40
6 F 46 0.6 Y Y Y pT3 14 20
7 F 59 0.7 N N N pT1 11 20
8 F 52 0.8 Y N Y pT3 8 20
9 F 62 1.2 N N N pT1 15 15
10 F 71 1.7 Y N N pT3 25 40
11 M 44 0.8 Y N N pT3 24 30
12 M 46 1.2 N N Y pT1 5 18
13 M 29 1.5 N N N pT1 12 3
14 F 35 2.0 N N N pT2 2 8
15 F 39 3.0 Y N N pT3 20 35
16 F 32 1.5 Y N N pT3 20 15
17 F 60 0.8 Y N Y pT3 30 12
18 F 40 1.5 Y N N pT3 20 30
19 F 35 0.5 N Y Y pT1 16 50
20 F 47 1.1 Y N N pT3 21 25
21 F 48 1.3 Y N N pT1 5 4
22 F 54 0.7 Y N Y pT3 25 17
23 M 38 1.5 N N N pT1 20 12
24 M 31 2.0 Y Y N pT3 30 18
25 F 39 1.0 Y Y N pT3 14 40
26 M 42 1.5 Y N Y pT3 21 35
27 F 39 1.0 N N N pT1 15 14
28 F 37 0.5 N N N pT1 1 1
29 F 36 3.0 Y Y N pT3 16 8
30 F 54 0.4 Y N N pT3 17 21
31 M 32 2.0 N Y N pT2 10 15
32 M 49 0.6 Y Y Y pT3 19 10
33 M 42 0.3 Y N N pT3 15 25
34 M 61 3.0 Y N Y pT3 22 49
35 M 50 1.0 Y N N pT3 30 4

* unit; cm.

† ET ext; extrathyroidal extension by AJCC criteria.

‡ LN meta; lymph node metastasis.

§ multi; multiplicity.

∥ The proportion of positive cells was calculated based on evaluation 100 malignant cells around invading fronts.

Table 2.
Relationship between S100A4 expression and the clinicopathological parameters
  High expression group Low expression group Total
Tumor size      
 ≤ 1.0 cm 7 11 18
 > 1 cm. 4 cm ≥ 7 10 17
 > 4.0 cm 0 0 0
Lymph node metastasis      
 Absent 10 17 27
 Present 3 5 8
Multiplicity      
 Absent 11 15 26
 Present 3 6 9
pT stage      
 1 1 9 10
 2 0 2 2
 3 13 10 23
Extrathyroidal extension      
 Absent 1 10 11
 Present 13 11 24
Table 3.
Relationship between COX2 expression and the clinicopathological parameters
  High expression group Low expression group Total
Tumor size      
 ≤ 1.0 cm 7 11 18
 > 1 cm. 4 cm ≥ 10 7 17
 > 4.0 cm 0 0 0
Lymph node metastasis      
 Absent 15 12 27
 Present 2 6 8
Multiplicity      
 Absent 12 14 26
 Present 5 4 9
pT stage      
 1 1 9 10
 2 0 2 2
 3 16 7 23
Extrathyroidal extension      
 Absent 1 10 11
 Present 16 8 24
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