The clinical features of papillary thyroid cancer in Hashimoto’s thyroiditis patients from an area with a high prevalence of Hashimoto’s disease

BMC Cancer

Ling Zhang¹  Hui Li¹  Qing-hai Ji¹  Yong-xue Zhu¹  Zhuo-ying Wang¹  Yu Wang¹  Cai-ping Huang¹  Qiang Shen¹  Duan-shu Li¹  Yi Wu¹ 

[1] Department of Head & Neck Surgery, Fudan University Cancer Hospital/Center, Department of oncology, Fudan University Shanghai Medical College, 270 Dong An Road, Shanghai, 200032, PR China

关键词: Hashimoto’s thyroiditis;    Thyroid-stimulating hormone;    Papillary thyroid carcinoma;   

Others  :  1080004
DOI  :  10.1186/1471-2407-12-610

 received in 2012-01-09, accepted in 2012-11-25,  发布年份 2012

【 摘 要 】

Background

The goal of this study was to identify the clinicopathological factors of co-existing papillary thyroid cancer (PTC) in patients with Hashimoto’s thyroiditis (HT) and provide information to aid in the diagnosis of such patients.

Methods

This study included 6109 patients treated in a university-based tertiary care cancer hospital over a 3-year period. All of the patients were categorised based on their final diagnosis. Several clinicopathological factors, such as age, gender, nodular size, invasive status, central compartment lymph node metastasis (CLNM) and serum thyroid-stimulating hormone (TSH) level, were compared between the various groups of patients.

Results

There were 653 patients with a final diagnosis of HT. More PTC was found in those with HT (58.3%; 381 of 653) than those without HT (2416 of 5456; 44.3%; p < 0.05). The HT patients with co-occurring PTC were more likely to be younger, be female, have smaller nodules and have higher TSH levels than those without PTC. A multivariate analysis indicated that the presence of HT and higher TSH levels were risk factors for a diagnosis of PTC. In the PTC patients, the presence of HT or another benign nodule was a protective factor for CLNM, whereas no significant association was found for TSH levels.

Conclusion

PTC and HT have a close relationship in this region of highly prevalent HT disease. Based on the results of our study, we hypothesise that long-term HT leads to elevated serum TSH, which is the real risk factor for thyroid cancer.

【 授权许可】

   
2012 Zhang et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61:69-90.
• [2]Kondo T, Ezzat S, Asa SL: Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer 2006, 6:292-306.
• [3]Gasbarri A, Sciacchitano S, Marasco A, Papotti M, Di Napoli A, Marzullo A, Yushkov P, Ruco L, Bartolazzi A: Detection and molecular characterisation of thyroid cancer precursor lesions in a specific subset of Hashimoto's thyroiditis. Br J Cancer 2004, 91:1096-1104.
• [4]Prasad ML, Huang Y, Pellegata NS, de la Chapelle A, Kloos RT: Hashimoto's thyroiditis with papillary thyroid carcinoma (PTC)-like nuclear alterations express molecular markers of PTC. Histopathology 2004, 45:39-46.
• [5]Lal G, Clark OH: Textbook of endocrine surgery. Philadelphia: Saunders; Chronic Thyroiditis; 2005:38-40.
• [6]Kumar V, Robbins SL: Robbins basic pathology. Philadelphia, PA: Saunders/Elsevier; 2007. [The endocrine system]
• [7]Teng W, Shan Z, Teng X, Guan H, Li Y, Teng D, Jin Y, Yu X, Fan C, Chong W, Yang F, Dai H, Yu Y, Li J, Chen Y, Zhao D, Shi X, Hu F, Mao J, Gu X, Yang R, Tong Y, Wang W, Gao T, Li C: Effect of iodine intake on thyroid diseases in China. Nengl J Med 2006, 354:2783-2793.
• [8]Dailey ME, Lindsay S, Skahen R: Relation of thyroid neoplasms to Hashimoto disease of the thyroid gland. AMA Arch Surg 1955, 70:291-297.
• [9]Hirabayashi RN, Lindsay S: The relation of thyroid carcinoma and chronic thyroiditis. Surg Gynecol Obstet 1965, 121:243-252.
• [10]Singh B, Shaha AR, Trivedi H, Carew JF, Poluri A, Shah JP: Coexistent Hashimoto's thyroiditis with papillary thyroid carcinoma: impact on presentation, management, and outcome. Surgery 1999, 126:1070-1076.
• [11]Ott RA, McCall AR, McHenry C, Jarosz H, Armin A, Lawrence AM, Paloyan E: The incidence of thyroid carcinoma in Hashimoto's thyroiditis. Am Surg 1987, 53:442-445.
• [12]Okayasu I, Fujiwara M, Hara Y, Tanaka Y, Rose NR: Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma. A study of surgical cases among Japanese, and white and African Americans. Cancer 1995, 76:2312-2318.
• [13]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 2008, 150:49-52.
• [14]Kim KW, Park YJ, Kim EH, Park SY, Park do J, Ahn SH, Park do J, Jang HC, Cho BY: Elevated risk of papillary thyroid cancer in Korean patients with Hashimoto's thyroiditis. Head Neck 2011, 33:691-695.
• [15]Haymart MR, Repplinger DJ, Leverson GE, Elson DF, Sippel RS, Jaume JC, Chen H: Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage. J Clin Endocrinol Metab 2008, 93:809-814.
• [16]Holm LE, Blomgren H, Lowhagen T: Cancer risks in patients with chronic lymphocytic thyroiditis. N Engl J Med 1985, 312:601-604.
• [17]Rago T, Di Coscio G, Ugolini C, Scutari M, Basolo F, Latofa F, Romani R, Berti P, Grasso L, Braverman LE, Pinchera A, Vitti P: Clinical features of thyroid autoimmunity are associated with thyroiditis on histology and are not predictive of malignancy in 570 patients with indeterminate nodules on cytology who had a thyroidectomy. Clin Endocrinol (Oxf) 2007, 67:363-369.
• [18]Crile G Jr: Struma lymphomatosa and carcinoma of the thyroid. Surg Gynecol Obstet 1978, 147:350-352.
• [19]Anil C, Goksel S, Gursoy A: Hashimoto's thyroiditis is not associated with increased risk of thyroid cancer in patients with thyroid nodules: a single-center prospective study. Thyroid 2010, 20:601-606.
• [20]Cipolla C, Sandonato L, Graceffa G, Fricano S, Torcivia A, Vieni S, Latteri S, Latteri MA: Hashimoto thyroiditis coexistent with papillary thyroid carcinoma. Am Surg 2005, 71:874-878.
• [21]Takahashi M, Buma Y, Iwamoto T, Inaguma Y, Ikeda H, Hiai H: Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains. Oncogene 1988, 3:571-578.
• [22]Tallini G, Asa SL: RET oncogene activation in papillary thyroid carcinoma. Adv Anat Pathol 2001, 8:345-354.
• [23]Tallini G, Santoro M, Helie M, Carlomagno F, Salvatore G, Chiappetta G, Carcanqiu ML, Fusco A: RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes. Clin Cancer Res 1998, 4:287-294.
• [24]Lam AK, Montone KT, Nolan KA, Livolsi VA: Ret oncogene activation in papillary thyroid carcinoma: prevalence and implication on the histological parameters. Hum Pathol 1998, 29:565-568.
• [25]Sugg SL, Ezzat S, Zheng L, Freeman JL, Rosen IB, Asa SL: Oncogene profile of papillary thyroid carcinoma. Surgery 1999, 125:46-52.
• [26]Musholt TJ, Musholt PB, Khaladj N, Schulz D, Scheumann GF, Klempnauer J: Prognostic significance of RET and NTRK1 rearrangements in sporadic papillary thyroid carcinoma. Surgery 2000, 128:984-993.
• [27]Nakazawa T, Kondo T, Kobayashi Y, Takamura N, Murata S, Kameyama K, Muramastsu A, Ito K, Kobayashi M, Katoh R: RET gene rearrangements (RET/ PTC1 and RET/PTC3) in papillary thyroid carcinomas from an iodine-rich country (Japan). Cancer 2005, 104:943-951.
• [28]Sheils OM, O'Eary JJ, Uhlmann V, Lattich K, Sweeney EC: Ret/PTC-1 activation in Hashimoto Thyroiditis. Int J Surg Pathol 2000, 8:185-189.
• [29]Wirtschafter A, Schmidt R, Rosen D, Kundu N, Santoro M, Fusco A, Multhaupt H, Atkins JP, Rosen MR, Keane WM, Rothstein JL: Expression of the RET/PTC fusion gene as a marker for papillary carcinoma in Hashimoto's thyroiditis. Laryngoscope 1997, 107:95-100.
• [30]Arif S, Blanes A, Diza-Cano SJ: Hshimoto’s thyroiditis share features with early papillary thyoid carcinoma. Histopathology 2002, 41:357-362.
• [31]Unger P, Ewart M, Wang BY, Gan L, Kohtz DS, Burstein DE: Expression of p63 in papillary thyroid carcinoma and in Hashimoto’s thyroiditis: a pathobiologic link? Hum Pathol 2003, 34:764-769.
• [32]Nikiforova MN, Caudill CM, Biddinger P, Nikiforova YE: Prevalence of RET/PTC rearrangements in Hashimoto’s thyroiditis and papillary thyroid carcinomas. Int J Surg Pathol 2002, 10:15-22.
• [33]Sugg SL, Ezzat S, Rosen IB, Freeman JL, Asa SL: Distinct multiple RET/PTC gene rearrangements in multifocal papillary thyroid neoplasia. J Clin Endocrinol Metab 1998, 83:4116-4122.
• [34]Boelaert K, Horacek J, Holder RL, Wtkinson JC, Sheppard MC, Franklyn JA: Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J Clin Endocrinol Metab 2006, 91:4295-4301.
• [35]Hovens GC, Stokkel MP, Kievit J, Corssmit EP, Pereira AM, Romijn JA, Smit JW: Associations of serum thyrotropin concentrations with recurrence and death in differentiated thyroid cancer. J Clin Endocrinol Metab 2007, 92:2610-2615.
• [36]Polyzos SA, Kita M, Efstathiadou Z, Slavakis A, Sofianou D, Flaris N, Leontsini M, Kourtis A, Avramidis A: Serum thyrotropin concentration as a biochemical predictor of thyroid malignancy in patients presenting with thyroid nodules. J Can Res Clin Onco 2008, 134:953-960.
• [37]Jonklaas J, Nsouli-Maktabi H, Soldin SJ: Endogenous thyrotropin and triiodothyronine concentrations in individuals with thyroid cancer. Thyroid 2008, 18:943-952.
• [38]Haymart MR, Glinberg SL, Liu J, Sippel RS, Jaume JC, Chen H: Higher serum TSH in thyroid cancer patients occurs independent of age and correlates with extrathyroidal extension. Clin Endocrinology(Oxf) 2009, 73:434-439.
• [39]Fiore E, Rago T, Provenzale MA, Scitari M, Uqolini C, Basolo F, Di coscio G, Berti P, Grasso L, Elisei R, Pinchera A, Vitti P: Lower levels of TSH are associated to a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role. Endocr Relat Cancer 2009, 16:1251-1260.
• [40]Jin J, Machekano R, McHenry CR: The utility of preoperative serum thyroid-stimulating hormone level for predicting malignant nodular thyroid disease. Am J Surg 2010, 199:294-298.
• [41]Kim ES, Lim DJ, Baek KH, Lee JM, Kim MK, Kwon HS, Song KH, Kang MI, Cha BY, Lee KW, Son HY: Thyroglobulin antibody is associated with increased cancer risk in thyroid nodules. Thyroid 2010, 20:885-891.
• [42]Gudmundsson J, Sulem P, Gudbjartsson DF, Jonasoon JG, Sigurdsson A, Bergthorsson JT, He H, Blondal T, Geller F, Jakobsdottir M, Magnusdottir DN, Matthiasdottir S, Stacey SN, Skarphedinsson OB, Helgadottir H, Li W, Nagy R, Aquillo E, Faure E, Prats E, Saez B, Martinez M, Eyjolfsson GI, Bjornsdottir US, Holm H, Kristjansson K, Frigge ML, Kristvinsson H, Gulcher JR, Jonsson T, et al.: Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations. Nat Genet 2009, 4:460-464.
• [43]Landa I, Ruiz-Llorente S, Montero-Conde C, Inglada-Pérez L, Schiavi F, Leskelä S, Pita G, Milne R, Maravall J, Ramos I, Andía V, Rodríguez-Poyo P, Jara-Albarrán A, Meoro A, del Peso C, Arribas L, Iglesias P, Caballero J, Serrano J, Picó A, Pomares F, Giménez G, López-Mondéjar P, Castello R, Merante-Boschin I, Pelizzo MR, Mauricio D, Opocher G, Rodríguez-Antona C, González-Neira A, et al.: The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors. PLoS Genet 2009, 5:e1000637.
• [44]Takahashi M, Saenko VA, Rogounovitch TI, Kawaguchi T, Drozd VM, Takigawa-Imamura H, Akulevich NM, Ratanajaraya C, Mitsutake N, Takamura N, Danilova LI, Lushchik ML, Demidchik YE, Heath S, Yamada R, Lathrop M, Matsuda F, Yamashita S: The FOXE1 locus is a major genetic determinant for radiation-related thyroid carcinoma in Chernobyl. Hum Mol Genet 2010, 19:2516-2523.
• [45]Biondi B, Filetti S, Schlumberger M: Thyroid hormone therapy and thyroid cancer: a reassessment. Nat Clin Pract Endocrinol Metab 2005, 1:32-40.
• [46]Kim EY, Kim WG, Kim WB, et al.: Coexistence of chronic lymphocytic thyroiditis is associated with lower recurrence rates in patients with papillary thyroid carcinoma. Clin Endocrinol (Oxf) 2009, 71:581-586.
• [47]Kim SS, Lee BJ, Lee JC, Song SH, Kim BH, Son SM, Kim IJ, Kim YK, Kang YH: Preoperative serum thyroid stimulating hormone levels in well-differentiated thyroid carcinoma is a predictive factor for lateral lymph node metastasis as well as extrathyroidal extension in Korean patients: a single-center experience. Endocrine 2011, 39:259-265.
• [48]Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell 2011, 144:646-674.
• [49]Grivennikov SI, Greten FR, Karin M: Immunity, inflammation, and cancer. Cell 2010, 140:883-899.
• [50]Qian BZ, Pollard JW: Macrophage diversity enhances tumor progression and metastasis. Cell 2010, 141:39-51.
• [51]Arora N, Scognamiglio T, Zhu B, Fahey TJ 3rd: Do benign thyroid nodules have malignant potential? An evidence-based review. World J Surg 2008, 32:1237-1246.
• [52]Zhang L, Wei WJ, Ji QH, Zhu YX, Wang ZY, Wang Y, Huang CP, Shen Q, Li DS, Wu Y: Risk factors for neck nodal metastasis in papillary thyroid microcarcinoma: a study of 1066 patients. J Clin Endocrinol Metab 2012, 97:1250-1257.