Cyclooxygenase‐2 expression in thyroid neoplasms

Ito, Yasuhiro; Yoshida, Hiroshi; Nakano, Keiichi; Takamura, Yuuki; Miya, Akihiro; Kobayashi, Kaoru; Yokozawa, Tamotsu; Matsuzuka, Fumio; Matsuura, Nariaki; Kuma, Kanji; Miyauchi, Akira

doi:10.1046/j.1365-2559.2003.01624.x

Cited by 49 publications

(54 citation statements)

References 28 publications

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“…COX-2 was most frequently upregulated in PTC compared with other types of thyroid malignancy (6 -10). COX-2 expression was detected in 84 of 108 (78%) (7), 4 of 5 (80%) (10), 40 of 49 (82%) (9), and 19 of 19 (100%) (8) PTC specimens using immunohistochemistry. Our study showed that COX-2 overexpression was frequently detected in the majority of patients with PTC using immunhistochem- istry but was absent in benign conditions including follicular adenoma and lymphocytic thyroiditis.…”

Section: Discussionmentioning

confidence: 99%

“…It was shown that COX-2 expression using immunohistochemistry was significantly lower in anaplastic and follicular carcinomas than in PTC (9). In addition, COX-2 expression in PTC was significantly reduced in cases with old age, large size, advanced stage, satellite tumors, and the presence of a solid, scirrhous or trabecular growth pattern (9).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, COX-2 expression in PTC was significantly reduced in cases with old age, large size, advanced stage, satellite tumors, and the presence of a solid, scirrhous or trabecular growth pattern (9). Therefore, it was suggested that COX-2 activation seemed to be involved in the early phase of pathogenesis of thyroid carcinoma (8,9).…”

Section: Discussionmentioning

confidence: 99%

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High prevalence of cyclooxygenase 2 expression in papillary thyroid carcinoma

Lo¹,

Lam²,

Leung³

et al. 2005

eur j endocrinol

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Background: Cyclooxygenase-2 (COX-2) seems to play a role in the development and carcinogenesis of papillary thyroid carcinoma. Its incidence of expression and potential application as a tumor marker remain to be elucidated. Materials and methods: Immunohistochemical staining for COX-2 expression was performed for 30 papillary thyroid carcinoma (PTC) and 40 benign thyroid specimens. COX-2 mRNA expression was analyzed using a reverse transcriptase-polymerase chain reaction (RT-PCR) for paired fresh frozen tissues removed from surgically resected PTC specimens. Results: COX-2 expression was detected by immunohistochemistry in 27 of 30 (90%) PTC but was absent in 40 benign thyroid specimens, including 27 nodular hyperplasia, 7 follicular adenoma and 6 lymphocytic thyroiditis. Two of the three COX-2 negative carcinomas were follicular variant of PTC. RT-PCR analysis confirmed COX-2 mRNA over-expression in 14 of 20 (70%) paired specimens of PTC. Real-time quantitative RT-PCR showed that the level of COX-2 mRNA expression was significantly higher in PTC than in both the adjacent non-cancerous tissues and the benign thyroid specimens. Conclusion: COX-2 is frequently expressed in PTC but not in benign thyroid specimens. COX-2 expression may serve as a useful molecular marker for PTC in cases of diagnostic difficulty.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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High prevalence of cyclooxygenase 2 expression in papillary thyroid carcinoma

Lo¹,

Lam²,

Leung³

et al. 2005

eur j endocrinol

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“…Other studies have also found variable levels of COX-2 proteins in papillary thyroid carcinomas. 29,36 Ito et al 29 found nine COX-2-negative cases (18.4%) among the 49 papillary carcinoma cases studied by immunohistochemistry. They showed that COX-2 levels varied with certain conditions and were significantly reduced in older patients, in patients with large tumors, and with advanced disease stages.…”

Section: In Vitro Studies Of the Cox-2 Inhibitor Ns-398mentioning

confidence: 99%

“…[26][27][28][29] Thyroid tumors generally express higher levels of COX-2 than normal tissues and thyroid tissues from patients with thyroiditis. [26][27][28][29] Thromboxane A2 (TXA 2 ) synthase and prostaglandin (PG) I 2 synthase are enzymes located downstream from COX-1 and COX-2, and catalyze synthesis of PG H, TXA 2 and PGI 2 ( Figure 1). TXA 2 stimulates platelet aggregation, while PGI 2 inhibits aggregation of platelets.…”

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confidence: 99%

Role of COX-2, thromboxane A2 synthase, and prostaglandin I2 synthase in papillary thyroid carcinoma growth

et al. 2005

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The development of papillary thyroid carcinoma is influenced by many factors including genetic alterations, growth factors, and physical agents such as radiation. Arachidonic acid and its derivatives including prostaglandins (PG) and thromboxane along with the enzymes involved in their synthesis have been shown to influence the growth of various tumors. We analyzed the immunoreactivity for cyclooxygenase-2 (COX-2) and mRNA expression levels of the enzymes COX-2, thromboxane A 2 (TXA 2 ) synthase, and PGI 2 synthase by RT-PCR in papillary carcinomas and matching normal tissues to determine the role of these enzymes in the development of papillary thyroid carcinomas. A papillary thyroid carcinoma cell line TPC-1 was also studied in vitro to determine the role of the specific COX-2 inhibitor NS-398 on COX-2 and vascular endothelial growth factor-A, since COX-2 also has a role in regulating tumor angiogenesis. RT-PCR analysis showed significant increases in TXA 2 synthase mRNA levels in papillary thyroid carcinomas compared to normal thyroid tissues. Although COX-2 mRNA levels were generally increased in papillary carcinomas, the differences were not statistically significant. There were no significant differences in PGI 2 synthase mRNA levels. COX-2 protein expression was greater in papillary carcinoma compared to normal thyroid tissues; however, the levels were quite variable. In vitro studies with a COX-2 inhibitor, NS-398, showed inhibition of tumor growth along with increased levels of COX-2 and vascular endothelial growth factor-A mRNA expression. These results indicate that specific enzyme levels in the PG synthesis pathway such as TXA 2 synthase are increased in papillary thyroid carcinomas. COX-2 also has a role in papillary thyroid growth, since a specific inhibitor of COX-2 regulates papillary thyroid carcinoma cell proliferation. These results implicate several enzymes in the synthesis of prostanoids as regulators of thyroid papillary carcinoma proliferation and suggest that increased levels of expression of these enzymes may play a role in the pathogenesis of these tumors.

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