Skip to main content
Top
Published in: Thyroid Research 1/2014

Open Access 01-12-2014 | Research

Assessment of cyclooxygenase-1 and 2 gene expression levels in chronic autoimmune thyroiditis, papillary thyroid carcinoma and nontoxic nodular goitre

Authors: Kinga Krawczyk-Rusiecka, Katarzyna Wojciechowska-Durczynska, Anna Cyniak-Magierska, Arkadiusz Zygmunt, Andrzej Lewinski

Published in: Thyroid Research | Issue 1/2014

Login to get access

Abstract

Introduction

The cyclooxygenases are a group of enzymes catalyzing the formation of prostaglandins from arachidonic acid. Cyclooxygenase-1 (COX-1) is a constitutive form, thought to be a “housekeeping gene”, with constant levels of expression in most tissues. COX-1 expression in the thyroid gland, except for medullary thyroid carcinoma, has not been a subject of much interest. Cyclooxygenase-2 (COX-2) can be expressed in response to various stimuli, such as mitogens, hormones, cytokines, growth factors. The product of COX-2 activity has been implicated in carcinogenesis.
Recent studies have shown that up-regulation of COX-2 is associated with numerous neoplasms. Hereby, we present a study analysing COX-1 and COX-2 expression in papillary thyroid carcinoma (PTC), Hashimoto thyroiditis (HT) and nontoxic nodular goitre (NNG) in fine needle aspiration biopsy (FNAB) washouts and in postoperative tissue.

Material and methods

Cytological specimens from 120 patients (105 females and 15 males) have been studied, including patients with HT, PTC and NNG. Moreover, we have examined postoperative tissue specimens from 51 patients with PTC and NNG.
The methods of molecular analysis have included extraction of total RNA from FNAB cytological material and postoperative tissues, spectrophotometric assessment of the RNA purity, cDNA synthesis in reverse transcription reaction and an analysis of genes expression data by real-time PCR.

Results

The performed analysis has revealed statistically significant higher expression level of the COX-2 gene in PTC group, in comparison with HT and NNG groups (in both cytological and postoperative material).
In PTC patients, COX-2 gene expression levels in the material obtained by FNAB were similar to those in the postoperative thyroid tissue.
No correlations between COX-2 gene expression level and TNM staging in PTC samples have been observed.
There were no correlations between COX-2 expression and anti-TPO antibodies level, or patient’s sex or age in the studied groups. Also, there were no correlations of COX-1 gene expression level among PTC, HT and NNG groups.

Conclusions

Our results suggest that COX-2 gene does not participate in the mechanisms involved in molecular association of HT with PTC. However, in case of PTC itself, it may play some role in neoplastic transformation.
Appendix
Available only for authorised users
Literature
1.
go back to reference Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 1971, 231: 232–235. 10.1038/newbio231232a0PubMedCrossRef Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 1971, 231: 232–235. 10.1038/newbio231232a0PubMedCrossRef
2.
go back to reference Burdan F, Chałas A, Szumiło J: Cyclooxygenase and prostanoids - biological implications. Postepy Hig Med Dosw (Online) 2006, 60: 129–141. Burdan F, Chałas A, Szumiło J: Cyclooxygenase and prostanoids - biological implications. Postepy Hig Med Dosw (Online) 2006, 60: 129–141.
3.
go back to reference Bell CD, Vidal S, Kovacs K, Horvath E, Rotondo F: An immunohistochemical survey of nine cases of medullary carcinoma of thyroid including reactivity for Cox-1 and Cox-2 enzymes. Endocr Pathol 2002, 13: 331–340. 10.1385/EP:13:4:331PubMedCrossRef Bell CD, Vidal S, Kovacs K, Horvath E, Rotondo F: An immunohistochemical survey of nine cases of medullary carcinoma of thyroid including reactivity for Cox-1 and Cox-2 enzymes. Endocr Pathol 2002, 13: 331–340. 10.1385/EP:13:4:331PubMedCrossRef
4.
go back to reference Quidville V, Segond N, Lausson S, Frenkian M, Cohen R, Jullienne A: 15-Hydroxyprostaglandin-dehydrogenase is involved in anti-proliferative effect of non-steroidal anti-inflammatory drugs COX-1 inhibitors on a human medullary thyroid carcinoma cell line. Prostaglandins Other Lipid Mediat 2006, 81: 14–30. 10.1016/j.prostaglandins.2006.06.004PubMedCrossRef Quidville V, Segond N, Lausson S, Frenkian M, Cohen R, Jullienne A: 15-Hydroxyprostaglandin-dehydrogenase is involved in anti-proliferative effect of non-steroidal anti-inflammatory drugs COX-1 inhibitors on a human medullary thyroid carcinoma cell line. Prostaglandins Other Lipid Mediat 2006, 81: 14–30. 10.1016/j.prostaglandins.2006.06.004PubMedCrossRef
5.
go back to reference Tsujii M, DuBois RN: Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 1995, 83: 493–501. 10.1016/0092-8674(95)90127-2PubMedCrossRef Tsujii M, DuBois RN: Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 1995, 83: 493–501. 10.1016/0092-8674(95)90127-2PubMedCrossRef
6.
go back to reference Sawaoka H, Tsuji S, Tsujii M, Gunawan ES, Sasaki Y, Kawano S, Hori M: Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo. Lab Invest 1999, 79: 1469–1477.PubMed Sawaoka H, Tsuji S, Tsujii M, Gunawan ES, Sasaki Y, Kawano S, Hori M: Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo. Lab Invest 1999, 79: 1469–1477.PubMed
7.
go back to reference Masferrer JL, Leahy KM, Koki AT, Zweifel BS, Settle SL, Woerner BM, Edwards DA, Flickinger AG, Moore RJ, Seibert K: Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 2000, 60: 1306–1311.PubMed Masferrer JL, Leahy KM, Koki AT, Zweifel BS, Settle SL, Woerner BM, Edwards DA, Flickinger AG, Moore RJ, Seibert K: Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 2000, 60: 1306–1311.PubMed
8.
go back to reference Ward EM, Jemal A, Chen A: Increasing incidence of thyroid cancer: is diagnostic scrutiny the sole explanation? Future Oncol 2010, 6: 185–188. 10.2217/fon.09.161PubMedCrossRef Ward EM, Jemal A, Chen A: Increasing incidence of thyroid cancer: is diagnostic scrutiny the sole explanation? Future Oncol 2010, 6: 185–188. 10.2217/fon.09.161PubMedCrossRef
9.
go back to reference Repplinger D, Bargren A, Zhang YW, Adler JT, Haymart M, Chen H: Is Hashimoto’s thyroiditis a risk factor for papillary thyroid cancer? J Surg Res 2007, 150: 49–52. 10.1016/j.jss.2007.09.020PubMedCentralPubMedCrossRef Repplinger D, Bargren A, Zhang YW, Adler JT, Haymart M, Chen H: Is Hashimoto’s thyroiditis a risk factor for papillary thyroid cancer? J Surg Res 2007, 150: 49–52. 10.1016/j.jss.2007.09.020PubMedCentralPubMedCrossRef
10.
go back to reference Matesa-Anińá D, Matesa N, Dabelińá N, Kusińá Z: Coexistence of papillary carcinoma and Hashimoto’s thyroiditis. Acta Clin Croat 2009, 48: 9–12. Matesa-Anińá D, Matesa N, Dabelińá N, Kusińá Z: Coexistence of papillary carcinoma and Hashimoto’s thyroiditis. Acta Clin Croat 2009, 48: 9–12.
11.
go back to reference Mazokopakis EE, Tzortzinis AA, Dalieraki-Ott EI, Tsartsalis AN, Syros PK, Karefilakis CM, Papadomanolaki MG, Starakis IK: Coexistence of Hashimoto’s thyroiditis with papillary thyroid carcinoma. a retrospective study. Hormones (Athens) 2010, 9: 312–317. 10.14310/horm.2002.1282CrossRef Mazokopakis EE, Tzortzinis AA, Dalieraki-Ott EI, Tsartsalis AN, Syros PK, Karefilakis CM, Papadomanolaki MG, Starakis IK: Coexistence of Hashimoto’s thyroiditis with papillary thyroid carcinoma. a retrospective study. Hormones (Athens) 2010, 9: 312–317. 10.14310/horm.2002.1282CrossRef
12.
go back to reference Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987, 162: 156–159. 10.1016/0003-2697(87)90021-2PubMedCrossRef Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987, 162: 156–159. 10.1016/0003-2697(87)90021-2PubMedCrossRef
13.
go back to reference Ito Y, Yoshida H, Nakano K, Takamura Y, Miya A, Kobayashi K, Yokozawa T, Matsuzuka F, Matsuura N, Kuma K, Miyauchi A: Cyclooxygenase-2 expression in thyroid neoplasms. Histopathology 2003, 42: 492–497. 10.1046/j.1365-2559.2003.01624.xPubMedCrossRef Ito Y, Yoshida H, Nakano K, Takamura Y, Miya A, Kobayashi K, Yokozawa T, Matsuzuka F, Matsuura N, Kuma K, Miyauchi A: Cyclooxygenase-2 expression in thyroid neoplasms. Histopathology 2003, 42: 492–497. 10.1046/j.1365-2559.2003.01624.xPubMedCrossRef
14.
go back to reference Krawczyk-Rusiecka K, Wojciechowska-Durczyńska K, Cyniak-Magierska A, Adamczewski Z, Gałecka E, Lewiński A: COX-2 expression in papillary thyroid carcinoma (PTC) in cytological material obtained by fine needle aspiration biopsy (FNAB). Thyroid Res 2011, 4: 3. 10.1186/1756-6614-4-3PubMedCentralPubMedCrossRef Krawczyk-Rusiecka K, Wojciechowska-Durczyńska K, Cyniak-Magierska A, Adamczewski Z, Gałecka E, Lewiński A: COX-2 expression in papillary thyroid carcinoma (PTC) in cytological material obtained by fine needle aspiration biopsy (FNAB). Thyroid Res 2011, 4: 3. 10.1186/1756-6614-4-3PubMedCentralPubMedCrossRef
15.
go back to reference Nose F, Ichikawa T, Fujiwara M, Okayasu I: Up-regulation of cyclooxygenase-2 expression in lymphotic thyroiditis and thyroid tumors. Am J Clin Pathol 2002, 117: 546–551. 10.1309/9CCJ-XQ8P-PMFM-M65KPubMedCrossRef Nose F, Ichikawa T, Fujiwara M, Okayasu I: Up-regulation of cyclooxygenase-2 expression in lymphotic thyroiditis and thyroid tumors. Am J Clin Pathol 2002, 117: 546–551. 10.1309/9CCJ-XQ8P-PMFM-M65KPubMedCrossRef
16.
go back to reference Siironen P, Ristimäki A, Narko K, Nordling S, Louhimo J, Andersson S, Haapiainen R, Haglund C: VEGF-C and COX-2 expression in papillary thyroid cancer. Endocr Relat Cancer 2006, 13: 465–473. 10.1677/erc.1.01114PubMedCrossRef Siironen P, Ristimäki A, Narko K, Nordling S, Louhimo J, Andersson S, Haapiainen R, Haglund C: VEGF-C and COX-2 expression in papillary thyroid cancer. Endocr Relat Cancer 2006, 13: 465–473. 10.1677/erc.1.01114PubMedCrossRef
17.
go back to reference Casey MB, Zhang S, Jin L, Kajita S, Lloyd RV: Expression of cyclooxygenase-2 and thromboxane synthase in non-neoplastic and neoplastic thyroid lesions. Endocr Pathol 2004, 15: 107–116. 10.1385/EP:15:2:107PubMedCrossRef Casey MB, Zhang S, Jin L, Kajita S, Lloyd RV: Expression of cyclooxygenase-2 and thromboxane synthase in non-neoplastic and neoplastic thyroid lesions. Endocr Pathol 2004, 15: 107–116. 10.1385/EP:15:2:107PubMedCrossRef
18.
go back to reference Cornetta AJ, Russell JP, Cunnane M, Keane WM: Rothstein Cyclooxygenase-2 expression in human thyroid carcinoma and Hashimoto’s thyroiditis. Laryngoscope 2002, 112: 238–242. 10.1097/00005537-200202000-00008PubMedCrossRef Cornetta AJ, Russell JP, Cunnane M, Keane WM: Rothstein Cyclooxygenase-2 expression in human thyroid carcinoma and Hashimoto’s thyroiditis. Laryngoscope 2002, 112: 238–242. 10.1097/00005537-200202000-00008PubMedCrossRef
19.
go back to reference Lee KJ, Jung YS, Kim WH, Yoon TI, Joo HJ, Soh EY: Cyclooxygenase-2 expression in human thyroid disease. J Endocrinol Invest 2008, 31: 111–118. 10.1007/BF03345576PubMedCrossRef Lee KJ, Jung YS, Kim WH, Yoon TI, Joo HJ, Soh EY: Cyclooxygenase-2 expression in human thyroid disease. J Endocrinol Invest 2008, 31: 111–118. 10.1007/BF03345576PubMedCrossRef
20.
go back to reference Specht MC, Tucker ON, Hocever M, Gonzalez D, Teng L, Fahey TJ 3rd: Cyclooxygenase-2 expression in thyroid nodules. J Clin Endocrinol Metab 2002, 87: 358–363. 10.1210/jcem.87.1.8179PubMedCrossRef Specht MC, Tucker ON, Hocever M, Gonzalez D, Teng L, Fahey TJ 3rd: Cyclooxygenase-2 expression in thyroid nodules. J Clin Endocrinol Metab 2002, 87: 358–363. 10.1210/jcem.87.1.8179PubMedCrossRef
21.
go back to reference Scarpino S, Duranti E, Giglio S, Di Napoli A, Galafate D, Del Bufalo D, Desideri M, Socciarelli F, Stoppacciaro A, Ruco L: Papillary carcinoma of the thyroid: high expression of COX-2 and low expression of KAI-1/CD82 are associated with increased tumor invasiveness. Thyroid 2013, 23: 1127–1137. 10.1089/thy.2011.0421PubMedCrossRef Scarpino S, Duranti E, Giglio S, Di Napoli A, Galafate D, Del Bufalo D, Desideri M, Socciarelli F, Stoppacciaro A, Ruco L: Papillary carcinoma of the thyroid: high expression of COX-2 and low expression of KAI-1/CD82 are associated with increased tumor invasiveness. Thyroid 2013, 23: 1127–1137. 10.1089/thy.2011.0421PubMedCrossRef
22.
go back to reference Garcia-Gonzales M, Abdulkader I, Vasquez Bouqete A, Neo XM, Forteza J, Cameselle-Teijeiro J: Cyclooxygenase-2 in normal, hyperplastic and neoplastic follicular cells of the human thyroid gland. Virchows Arch 2005, 447: 12–17. 10.1007/s00428-005-1235-1CrossRef Garcia-Gonzales M, Abdulkader I, Vasquez Bouqete A, Neo XM, Forteza J, Cameselle-Teijeiro J: Cyclooxygenase-2 in normal, hyperplastic and neoplastic follicular cells of the human thyroid gland. Virchows Arch 2005, 447: 12–17. 10.1007/s00428-005-1235-1CrossRef
23.
go back to reference Wojciechowska-Durczyńska K, Krawczyk-Rusiecka K, Cyniak-Magierska A, Zygmunt A, Gałecka E, Lewiński A: Relative quantification of PIK3CA gene expression level in fine-needle aspiration biopsy thyroid specimens collected from patients with papillary thyroid carcinoma and non-toxic goitre by real-time RT-PCR. Thyroid Res 2010, 3: 5. 10.1186/1756-6614-3-5PubMedCentralPubMedCrossRef Wojciechowska-Durczyńska K, Krawczyk-Rusiecka K, Cyniak-Magierska A, Zygmunt A, Gałecka E, Lewiński A: Relative quantification of PIK3CA gene expression level in fine-needle aspiration biopsy thyroid specimens collected from patients with papillary thyroid carcinoma and non-toxic goitre by real-time RT-PCR. Thyroid Res 2010, 3: 5. 10.1186/1756-6614-3-5PubMedCentralPubMedCrossRef
24.
go back to reference Wojciechowska-Durczyńska K, Krawczyk-Rusiecka K, Cyniak-Magierska A, Zygmunt A, Dedecjus M, Lewiński A: Is the PIK3CA gene expression in FNAB washouts equivalent to that in postoperative tissue specimens of papillary thyroid carcinoma? Neur Endocrinol Lett 2011, 32: 59–63. Wojciechowska-Durczyńska K, Krawczyk-Rusiecka K, Cyniak-Magierska A, Zygmunt A, Dedecjus M, Lewiński A: Is the PIK3CA gene expression in FNAB washouts equivalent to that in postoperative tissue specimens of papillary thyroid carcinoma? Neur Endocrinol Lett 2011, 32: 59–63.
25.
go back to reference Karmisholt JS, Andersen S, Laurberg P: Variation in thyroid function in subclinical hypothyroidism: importance for clinical follow-up and therapy. Eur J Endocrinol 2011, 164: 317–323. 10.1530/EJE-10-1021PubMedCrossRef Karmisholt JS, Andersen S, Laurberg P: Variation in thyroid function in subclinical hypothyroidism: importance for clinical follow-up and therapy. Eur J Endocrinol 2011, 164: 317–323. 10.1530/EJE-10-1021PubMedCrossRef
26.
go back to reference Lee HM, Baek SK, Kwon SY, Jung KY, Chae SW, Hwang SJ, Woo JS, Lee JY: Cyclooxygenase 1 and 2 expressions in the human thyroid gland. Eur Arch Otorhinolaryngol 2006, 263: 199–204. 10.1007/s00405-005-0999-xPubMedCrossRef Lee HM, Baek SK, Kwon SY, Jung KY, Chae SW, Hwang SJ, Woo JS, Lee JY: Cyclooxygenase 1 and 2 expressions in the human thyroid gland. Eur Arch Otorhinolaryngol 2006, 263: 199–204. 10.1007/s00405-005-0999-xPubMedCrossRef
Metadata
Title
Assessment of cyclooxygenase-1 and 2 gene expression levels in chronic autoimmune thyroiditis, papillary thyroid carcinoma and nontoxic nodular goitre
Authors
Kinga Krawczyk-Rusiecka
Katarzyna Wojciechowska-Durczynska
Anna Cyniak-Magierska
Arkadiusz Zygmunt
Andrzej Lewinski
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Thyroid Research / Issue 1/2014
Electronic ISSN: 1756-6614
DOI
https://doi.org/10.1186/s13044-014-0010-2

Other articles of this Issue 1/2014

Thyroid Research 1/2014 Go to the issue