갑상샘 유두암종에서 S100A4 및 COX2 발현과 침윤성과의 관련성 = Correlation between S100A4 and COX2 Overexpression and Invasiveness of Papillary Thyroid Carcinoma

다국어 초록 (Multilingual 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. (J Korean Endocr Soc 23:186~192, 2008)

참고문헌 (Reference)

1 Hermanek P, "TNM classification of malignant tumours" Springer-Verlag 77-87, 1992

2 Zou M, "S100A4(Mts I) gene overexpression is associated with invasion and metastasis of papillary thyroid carcinoma" 93 : 1277-1284, 2005

3 Ito Y, "S100A4 expression is an early event of papillary carcinoma of the thyroid" 67 : 397-402, 2004

4 Kajita S, "Role of COX-2, thromboxane A2 synthase, and prostaglandin I2 synthase in papillary thyroid carcinoma growth" 18 : 221-227, 2005

5 Rudland PS, "Prognostic significance of the metastasis-inducing protein S100A4(p9Ka) in human breast cancer" 60 : 1595-1603, 2000

6 Siironen P, "Prognostic factors in papillary thyroid cancer: an evaluation of 601 consecutive patients" 26 : 57-64, 2005

7 Cho YG, "Overexpression of S100A4 is closely related to the aggressiveness of gastric cancer" 111 : 539-545, 2003

8 Rosty C, "Overexpression of S100A4 in pancreatic ductal adenocarcinoma is associated with poor differentiation and DNA hypomethylation" 160 : 45-50, 2002

9 DeGroot LJ, "Natural history, treatment, and course of papillary thyroid carcinoma" 71 : 414-424, 1990

10 Zou M, "Microarray analysis of metastasis-associated gene expression profiling in a murine model of thyroid carcinoma pulmonary metastasis: identification of S100A4 (Mts1) gene overexpression as a poor prognostic marker for thyroid carcinoma" 89 : 6146-6154, 2004

11 Nakamura T, "Maeda S, Ku Y, Kuroda Y: Prognostic significance of S100A4 expression in gallbladder cancer" 20 : 937-941, 2002

12 Komatsu K, "Ishiguro S, Hunai H, Suzuki N, Kameyama M, Murata K, Miyoshi J, Akedo H, Tatsuta M, Nakamura H: Increased expression of S100A6 at the invading fronts of the primary lesion and liver metastasis in patients with colorectal adenocarcinoma" 83 (83): 769-774, 2000

13 Takenaga K, "Increased expression of S100A4, a metastasis-associated gene, in human colorectal adenocarcinomas" 3 : 2309-2316, 1997

14 Takenaga K, "Increased expression of S100A4, a metastasis-associated gene, in human colorectal adenocarcinomas" 3 : 2309-2316, 1997

15 Ninomiya I, "Increased expression of S100A4 and its prognostic significance in esophageal squamous cell carcinoma" 18 : 715-720, 2001

16 Lo CY, "High prevalence of cyclooxygenase 2 expression in papillary thyroid cacinoma" 152 : 545-550, 2005

17 Davies BR, "Expression of S100A4 protein is associated with metastasis and reduced survival in human bladder cancer" 196 : 292-299, 2002

18 Kohya N, "Effects of E-cadherin transfection on gene expression of a gallbladder carcinoma cell line: repression of MTS1/ S100A4 gene expression" 104 (104): 44-53, 2003

19 Andersen PE, "Differentiated carcinoma of the thyroid with extrathyroidal extension" 170 : 467-470, 1995

20 Gupta S, "Differential expression of S100A2 and S100A4 during progression of human prostate adenocarcinoma" 21 : 106-112, 2003

21 Garca-Gonzlez M, "Cyclooxygenase-2 in normal, hyperplastic and neoplastic follicular cells of the human thyroid gland" 447 : 12-17, 2005

22 Lee HM, "Cyclooxygenase 1 and 2 expressions if the human thyroid gland" 263 : 199-204, 2006

23 Barraclough R, "Calcium-binding protein S100A4 in health and disease" 1448 : 190-199, 1998

24 Singh B, "COX-2 overexpression increases motility and invasion of breast cancer cells" 26 : 1393-1399, 2005

25 Greene, "AJCC cancer staging manual, sixth edition" Springer-Verlag 67-72, 2006