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Nitrotyrosine, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) are increased in thyroid tumors from children and adolescents

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Abstract

Nitric oxide (NO) is a reactive cell signal that controls vascular tone and is generated by inducible (iNOS), endothelial (eNOS) and neuronal (nNOS) NO synthase (NOS). We hypothesized that NO could be important for growth of thyroid tumors and tested this hypothesis, by staining 41 papillary thyroid carcinoma (PTC), 9 follicular thyroid carcinoma (FTC), and 15 benign thyroid lesions for iNOS, eNOS and nitrotyrosine (N-TYR). Staining intensity was determined by 2 blinded, independent examiners, and quantified from grade 1 (absent) to grade 4 (intense). Average N-TYR staining of benign adenomas (2.5±0.42, p=0.009), PTC (3.10±0.12, p=0.001), FTC (2.44±0.30, p=0.001), and autoimmune lesions (3.25±0.48, p=0.019) were greater than that of multinodular goiter (1.0 for all 3) and surrounding normal thyroid (1.1±0.1). Average iNOS staining of benign adenomas (2.6±0.37), PTC (2.7±0.16), FTC (2.4±0.26) and autoimmune lesions (3.5±0.29) were all greater than that of surrounding normal thyroid (1.1±0.1, p<0.008), but there were too few multinodular goiters to achieve a significant difference (no.=2, 3.0±1.0). Average eNOS staining of benign adenomas (2.9±0.40), multinodular goiters (3.5±0.5), PTC (3.24±0.18), FTC (3.5±0.50), and autoimmune lesions (2.8±0.6) were also greater than that of surrounding normal thyroid (mean= 1.4±0.2, p<0.001). N-TYR staining correlated with that of vascular endothelial growth factor (VEGF, r=0.36, p=0.007) and the number of lymphocytes/high power field (r=0.39, p=0.004). Recurrent disease developed only from carcinoma with moderate-intense N-TYR staining, but there were too few recurrent tumors to achieve statistical significance (p=0.08). We conclude that NO is produced by benign adenomas, PTC and FTC suggesting that NO could be important in vascularization of thyroid tumors and autoimmune thyroid diseases.

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Authors and Affiliations

  1. Department of Pediatrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD, USA

    A. Patel, C. Fenton, R. Terrell, P. A. Powers, C. Dinauer &  G. L. Francis (Professor)

  2. Walter Reed Army Medical Center, Department of Pediatrics, Washington, DC, USA

    C. Fenton, P. A. Powers, C. Dinauer &  G. L. Francis (Professor)

  3. Walter Reed Army Medical Center, Department of Clinical Investigation, Washington, DC, USA

    A. Patel, R. Terrell & C. Dinauer

  4. Endocrinology Section Memorial Sloan Kettering Cancer Center, New York, NY, USA

    R. M. Tuttle

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  1. A. Patel
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  2. C. Fenton
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Correspondence to G. L. Francis.

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The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or to reflect the opinions of the Uniformed Services University of the Health Sciences, the Department of the Army, or the Department of Defense.

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Patel, A., Fenton, C., Terrell, R. et al. Nitrotyrosine, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) are increased in thyroid tumors from children and adolescents. J Endocrinol Invest 25, 675–683 (2002). https://doi.org/10.1007/BF03345100

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