There are conflicting reports in the literature regarding the prognostic influence of pregnancy on patients with papillary thyroid carcinoma (PTC), and there is no literature on specific microRNA (miRNA) profiles of PTC in the context of pregnancy. We aim to examine clinically if pregnancy is an adverse factor in PTC, and if pregnancy-associated PTC are biologically different from those in nonpregnant women in terms of their miRNA profiles.
Women diagnosed with PTC during or soon after pregnancy were recruited into the pregnancy group. Age-matched nonpregnant females were recruited into the nonpregnancy group. MiRNA microarray was performed on PTC tissue of pregnant patients (10), nonpregnant patients (10), and normal thyroids (5). There were 6 differentially expressed miRNAs from the microarray comparisons validated with RT-PCR.
There were 24 patients in the clinical pregnancy group and 30 in the nonpregnancy group. Tumors from the pregnancy group were significantly larger and showed more regional lymph node metastases. The microarray data showed a total of 27 miRNAs that were potential differentiators of PTC tissue samples from pregnant and nonpregnant patients. Of the 6 selected for validation, no significant difference in expression was found.
Our clinical data suggests that PTC during pregnancy may be more locoregionally aggressive. However, no difference in survival or recurrence is demonstrated. The miRNA profiles of the pregnancy-associated PTC have not been shown to be different to the nonpregnancy counterparts. This likely suggests that the differences seen clinically are related to patient factors rather than the disease itself.
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Howlader N, Noone A, Krapcho M, Neyman N, Aminou R, Waldron W, et al., editors. Thyroid [Internet]. SEER cancer statistics review. Bethesda: National Cancer Institute; 1975–2008. p. 1–27. http://seer.cancer.gov/csr/1975_2008. Accessed 4 April 2012.
Tracey E, Kerr T, Dobrovic A, Currow D, editorss. Cancer in NSW: incidence and mortality report 2008. Sydney: Cancer Institute NSW; 2010. p. 1–176.
Yasmeen S, Cress R, Romano P, Xing G, Berger-Chen B, Danielsen B, et al. Thyroid cancer in pregnancy. Int J Gynaecol Obstet. 2005;91:15–20.
Rosen IB, Walfish PG. Pregnancy as a predisposing factor in thyroid neoplasia. Arch Surg. 1986;121:1287–90.
Kobayashi K, Tanaka Y, Ishiguro S, Mori T. Rapidly growing thyroid carcinoma during pregnancy. J Surg Oncol. 1994;55:61–4.
Hirsch D, Levy S, Tsvetov G, Weinstein R, Lifshitz A, Singer J, et al. Impact of pregnancy on outcome and prognosis of survivors of papillary thyroid cancer. Thyroid. 2010;20:1179–85.
Nam KH, Yoon JH, Chang H-S, Park CS. Optimal timing of surgery in well-differentiated thyroid carcinoma detected during pregnancy. J Surg Oncol. 2005;91:199–203.
Herzon FS, Morris DM, Segal MN, Rauch G, Parnell T. Coexistent thyroid cancer and pregnancy. Arch Otolaryngol Head Neck Surg. 1994;120:1191–3.
Moosa M, Mazzaferri E. Outcome of differentiated thyroid cancer diagnosed in pregnant women. J Clin Endocrinol Metab. 1997;82:2862–6.
Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21:1081–125.
Vannucchi G, Perrino M, Rossi S, Colombo C, Vicentini L, Dazzi D, et al. Clinical and molecular features of differentiated thyroid cancer diagnosed during pregnancy. Eur J Endocrinol. 2009;162:145–51.
Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–5.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.
Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 2011;39(Database issue):D152–7.
miRBase: the microRNA database, release 19. [Internet] http://www.mirbase.org. Accessed 3 Aug 2012.
Rosenfeld N, Aharonov R, Meiri E, Rosenwald S, Spector Y, Zepeniuk M, et al. MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol. 2008;26:462–9.
Pallante P, Visone R, Croce CM, Fusco A. Deregulation of microRNA expression in follicular cell-derived human thyroid carcinomas. Endocr Relat Cancer. 2010;17:F91–F104.
Gao Y, Wang C, Shan Z, Guan H, Mao J, Fan C, et al. miRNA expression in a human papillary thyroid carcinoma cell line varies with invasiveness. Endocr J. 2010;57:81–6.
Liu A, Xu X. MicroRNA isolation from formalin-fixed, paraffin-embedded tissues. Methods Mol Biol. 2011;724:259–67.
Xi Y, Nakajima G, Gavin E, Morris CG, Kudo K, Hayashi K, et al. Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA. 2007;13:1668–74.
Smith LH, Danielsen B, Allen ME, Cress R. Cancer associated with obstetric delivery: results of linkage with the California cancer registry. Am J Obstet Gynecol. 189:1128–35.
Kung AWC. The effect of pregnancy on thyroid nodule formation. J Clin Endocrinol Metab. 2002;87:1010–4.
Ron E, Kleinerman R, Boice JJ, LiVolsi V, Rannery J, Fraumeni JJ. A population-based case-control study of thyroid cancer. J Natl Cancer Inst. 1987;79:1–12.
Przybylik-Mazurek E, Hubalewska-Dydejczyk A, Fedorowicz A, Pach D. Factors connected with the female sex seem to play an important role in differentiated thyroid cancer. Gynecol Endocrinol. 2012;28:150–5.
Chen GG, Vlantis AC, Zeng Q, van Hasselt CA. Regulation of cell growth by estrogen signaling and potential targets in thyroid cancer. Curr Cancer Drug Targets. 2008;8:367–77.
Zeng Q, Chen GG, Vlantis AC, van Hasselt CA. Oestrogen mediates the growth of human thyroid carcinoma cells via an oestrogen receptor-ERK pathway. Cell Prolif. 2007;40:921–35.
Manole D, Schildknecht B, Gosnell B, Adams E, Derwahl M. Estrogen promotes growth of human thyroid tumor cells by different molecular mechanisms. J Clin Endocrinol Metab. 2001;86:1072–7.
Vaiman M, Olevson Y, Habler L, Kessler A, Zehavi S, Sandbank J. Diagnostic value of estrogen receptors in thyroid lesions. Med Sci Monit. 2010;16:BR203–7.
Truong T. Role of goiter and of menstrual and reproductive factors in thyroid cancer: a population-based case-control study in New Caledonia (South Pacific), a very high incidence area. Am J Epidemiol. 2005;161:1056–65.
Di Vito M, De Santis E, Perrone GA, Mari E, Giordano MC, De Antoni E, et al. Overexpression of estrogen receptor-α in human papillary thyroid carcinomas studied by laser- capture microdissection and molecular biology. Cancer Sci. 2011;102:1921–7.
Hershman JM. Physiological and pathological aspects of the effect of human chorionic gonadotropin on the thyroid. Best Pract Res Clin Endocrinol Metab. 2004;18:249–65.
Zamperini P, Gibelli B, Gilardi D, Tradati N, Chiesa F. Pregnancy and thyroid cancer: ultrasound study of foetal thyroid. Acta Otorhinolaryngol Ital. 2009;29:339–44.
James Lee was funded by the University of Sydney Medical School Surgery Scholarship during the preparation of this manuscript, as part of a Doctor of Philosophy degree.
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Lee, J.C., Zhao, J.T., Clifton-Bligh, R.J. et al. Papillary Thyroid Carcinoma in Pregnancy: A Variant of the Disease?. Ann Surg Oncol 19, 4210–4216 (2012). https://doi.org/10.1245/s10434-012-2556-3
- Thyroid Cancer
- Papillary Thyroid Cancer
- Papillary Thyroid Cancer
- Multinodular Goiter
- Pregnancy Group