Age-dependent variation of follicular size and expression of iodine transporters in human thyroid tissue (original) (raw)
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The Journal of Clinical Endocrinology & Metabolism, 2006
Context: The thyroid gland is vulnerable to the carcinogenic effects of ionizing radiation, and there is a well-documented inverse correlation between thyroid cancer and age at exposure, particularly for ages less than 20 yr. One of the factors responsible for this phenomenon may be more rapid cell proliferation in children. Objective: The objective of this study was to determine the proliferative rate of normal human thyroid cells in different age groups. Design: We used immunohistochemical analysis to determine the Ki-67 proliferative index in 117 thyroid glands obtained at autopsy, including 25 fetal thyroids (11–40 wk gestation), 55 childhood thyroids (0–19 yr), and 37 adult thyroids (20–60 yr). Results: The rate of Ki-67 labeling in the three groups was 7.4 ± 6.10, 0.23 ± 0.15, and 0.08 ± 0.04% respectively, demonstrating an overall trend for diminishing proliferative activity of thyroid cells with increasing age. However, a lack of correlation was noted between the slopes of c...
Pediatric Research, 2002
The sodium-iodide symporter (NIS) is expressed by papillary (PTC) and follicular (FTC) thyroid carcinoma, and is essential for iodine uptake. We hypothesized that PTC and FTC with detectable NIS immunostaining would be more amenable to radioactive iodine ( 131 I) treatment and follow a more benevolent course. To test this, we determined NIS expression by immunohistochemistry in 23 PTC, 9 FTC, and 12 benign thyroid lesions from children and adolescents. NIS expression was determined by two blinded examiners and graded as absent ϭ 0, minimal ϭ 1, moderate ϭ 2, intense ϭ 3, and very intense ϭ 4. NIS was detected in 35% (eight of 23) of PTC, 44% (four of 9) of FTC, 25% (two of eight) of benign tumors, and 100% (four of four) of autoimmune lesions. The intensity of NIS expression was similar in PTC (0.61 Ϯ 0.24), FTC (0.56 Ϯ 0.24), and benign tumors (0.50 Ϯ 0.33) but was more intense in autoimmune lesions (3.0 Ϯ 0.7, p Ͻ 0.005). Distant metastases were found only among PTC with undetectable NIS (two of 15, 13%), and recurrence developed exclusively from PTC and FTC with undetectable NIS (four of 20, 20% versus zero of 12, p ϭ 0.043). The dose of iodine 131 required to achieve remission in the five patients with PTC who had undetectable NIS (213.3 Ϯ 53 mCi) was greater than that required by patients with similar age and extent of disease for whom NIS expression is unknown (109 Ϯ 22 mCi, p ϭ 0.06). We conclude that NIS expression is associated with a lower risk of recurrence for PTC and FTC of children and adolescents. Abbreviations NIS, sodium-iodide symporter PTC, papillary thyroid carcinoma FTC, follicular thyroid carcinoma TTF-1, thyroid transcription factor-1 PAX-8, paired-domain transcription factor-8 GTP s␣ , stimulatory alpha subunit of guanosine triphosphate binding protein ret/PTC, rearrangement of ret protooncogene MACIS, metastasis-age-completeness-of-resection-invasionsize Tg, thyroglobulin ABSTRACT 737
Clinical Endocrinology, 2009
Context Children present a higher susceptibility to developing thyroid cancer after radioiodine exposure and also a higher frequency of functional metastases than adults. Objective To assess the mRNA expression of the sodium/iodide (Na + /I-) symporter (NIS), the Pendred syndrome gene (PDS), thyroperoxidase (TPO), thyroglobulin (Tg) and TSH receptor (TSH-R) in normal thyroid tissues (NTTs) and papillary thyroid carcinomas (PTCs) among different age groups. Methods Analysis included 59 samples: 21 NTTs and 38 PTCs, of which 21 were the classic type (CPTC) and 17 the follicular variant (FVPTC). Patients were divided into three age groups: I (n = 16) 5-21 years, II (n = 13) 22-59 years, and III (n = 10) 60-91 years. The relative mRNA expression of the five target genes was determinate by quantitative reverse transcription polymerase chain reaction (QRT-PCR). Results Expression of all genes was significantly higher in NTTs than in PTCs, and it was not age dependent in the NTT group. Among PTCs, the mean expression of PDS, TPO and TSH-R was significantly lower in group II than in group I. PDS, TPO and Tg expression was significantly lower in classic PTCs than in FVPTCs. The difference was related to a higher frequency of the BRAF V600E mutation in the former group. Conclusions The finding of higher PDS, TPO and TSH-R mRNA expression in paediatric vs. adult primary tumour tissues supports the hypothesis that this might contribute to the increased functional activity of metastases in the paediatric group. The finding that mRNA expression of the target genes in NTT was not age dependent does not provide an explanation for the higher susceptibility in the paediatric group.
Radiotherapyinduced structural and functional changes in the thyroid gland
Background: Despite their specific functional hazards, radiotherapy induced thyroid disorders remain underevaluated, even though, various types of irradiation caused either benign and malignant changes of the thyroid gland have been mentioned in this study. Aim: To report the current status concerning the hazards of various types of irradiation on the detection of different thyroid abnormalities either benign and/or malignant changes.
Radiotherapy-Induced Structural and Functional Changes in the Thyroid Gland Citation
Background: Despite their specific functional hazards, radiotherapy induced thyroid disorders remain underevaluated, even though, various types of irradiation caused either benign and malignant changes of the thyroid gland have been mentioned in this study. Aim: To report the current status concerning the hazards of various types of irradiation on the detection of different thyroid abnormalities either benign and/or malignant changes.
Thyroid, 2007
Several studies have demonstrated that moderately high concentrations of molecular iodine (I 2 ) diminish the symptoms of mammary fibrosis in women, reduce the occurrence of mammary cancer induced chemically in rats (50-70%), and have a clear antiproliferative and apoptotic effect in the human tumoral mammary cell line MCF-7. Nevertheless, the importance of these effects has been underestimated, in part because of the notion that exposure to excess iodine represents a potential risk to thyroid physiology. In the present work we demonstrate that uptake and metabolism of iodine differ in an organ-specific manner and also depend on the chemical form of the iodine ingested (potassium iodide vs. I 2 ). Further, we show that a moderately high I 2 supplement (0.05%) causes some of the characteristics of the ''acute Wolff-Chaikoff effect''; namely, it lowers expression of the sodium=iodide symporter, pendrin, thyroperoxidase (TPO), and deiodinase type 1 in thyroid gland without diminishing circulating levels of thyroid hormone. Finally, we confirm that I 2 metabolism is independent of TPO, and we demonstrate that, at the doses used here, which are potentially useful to treat mammary tumors, chronic I 2 supplement is not accompanied by any harmful secondary effects on the thyroid or general physiology. Thus, we suggest that I 2 could be considered for use in clinical trials of breast cancer therapies.
Effects of radioactive iodine (131I) on the thyroid of newborn, pubertal and adult rats
International Congress Series, 2002
Age is a potent modifier of thyroid cancer. The short latency for the development of thyroid cancer in the post-Chernobyl cases proposes that we need to be sure of the thyroid susceptibility to internal exposure, especially at young ages. We started a large-scale carcinogenesis project 6 years ago with the purpose to evaluate the carcinogenic potential of 131 I when irradiated at young ages. First, we established a method to estimate the absorbed doses in the thyroid of different age groups. Irradiation at 1 week of age caused heavier exposure than at 4 and 9 weeks of age by eight times, while damages of the thyroid tissue were more obvious in the 4-week-old groups than in the 1-weekold groups. Second, we tested the responsiveness of thyroid epithelium to radiation. Apoptosis was not detected in the 1-week-old-thyroid epithelium, however, it did appear in the 4-week-old thyroid epithelium. While the proliferating cell nuclear antigen (PCNA)-labeling index was vice versa. Third, the carcinogenesis of 131 I has been tested. Papillary carcinomas have developed in rats internally irradiated with 131 I at the age of 1 week. A very low dose rate of irradiation by 131 I could induce thyroid carcinomas with a short latency.
The Journal of Clinical Endocrinology & Metabolism, 2003
Mono-or polyclonal antibodies are now available to detect on histological sections the Na ؉ /I ؊ symporter (NIS) at the basolateral pole of the cell, the putative iodide channel (pendrin) at the apical plasma membrane, thyroperoxidase (TPO), and members of the NADPH-oxidase family, thyroid oxidase 1 and 2 (ThOXs), part of the H 2 O 2 -generating system. The aim of this study was to correlate thyroglobulin (Tg) iodination with the presence of these proteins. Tg, T 4 -containing Tg, NIS, pendrin, TPO, ThOXs, and TSH receptor (TSHr) were detected by immunohistochemistry on tissue sections of normal thyroids and various benign and malignant thyroid disorders. Tg was present in all cases. T 4 -containing Tg was found in the adenomas, except in Hurthle cell adenomas. It was never detected in carcinomas. NIS was reduced in all types of carcinomas, whereas it was detected in noncancerous tissues. Pendrin was not expressed in carcinomas, except in follicular carcinomas, where weak staining persisted. TPO expression was present in insular, follicular carcinomas and in follicular variants of papillary carcinomas, but in a reduced percentage of cells. It was below the level of detection in papillary carcinomas. The H 2 O 2 -generating system, ThOXs, was found in all carcinomas and was even increased in papillary carcinomas. Its staining was apical in normal thyroids, whereas it was cytoplasmic in carcinomas. The TSHr was expressed in all cases, but the intensity of the staining was decreased in insular carcinomas.
Radiation exposure and thyroid cancer: a review
Archives of endocrinology and metabolism
The association between radiation exposure and the occurrence of thyroid cancer has been well documented, and the two main risk factors for the development of a thyroid cancer are the radiation dose delivered to the thyroid gland and the age at exposure. The risk increases after exposure to a mean dose of more than 0.05-0.1 Gy (50-100mGy). The risk is more important during childhood and decreases with increased age at exposure, being low in adults. After exposure, the minimum latency period before the appearance of thyroid cancers is 5 to 10 years. Papillary carcinoma (PTC) is the most frequent form of thyroid carcinoma diagnosed after radiation exposure, with a higher prevalence of the solid subtype in young children with a short latency period and of the classical subtype in cases with a longer latency period after exposure. Molecular alterations, including intra-chromosomal rearrangements, are frequently found. Among them, RET/PTC rearrangements are the most frequent. Current res...
Thyroid gland and radiation (fundamental and applied aspects): 20 years after the Chernobyl accident
International Congress Series, 2007
In the present paper are generalized data on the increase of thyroid cancer incidence in children and adolescents affected after the Chernobyl accident for the period 1986-2004. Beginning in 1990, a significant rise in the number of thyroid cancer cases and incidence was noted in the cohort aged 0-18 years at the time of the accident, especially among children aged 0-14 years. Patients' distribution by age at the time of the accident points out that the most significant increase in the number of thyroid cancer patients occurred at the expense of children who were aged up to 4 years in 1986. This is confirmed by the data concerning a steady increase just among children aged 0-4 years at the time of the accident, of additional thyroid cancer incidence with increasing thyroid exposure dose. The most pronounced increase has been reported for the highest average thyroid exposure dose of 1 Gy and more. The principles of early diagnosis of thyroid carcinoma lie in an objective assessment of oncological danger from all focal lesions of the thyroid, which were detected by ultrasound investigation. FNA of these tumors with cytology study of cell material allows improvement in the accuracy of preoperative diagnosis of thyroid cancer. The method of choice in the treatment of thyroid cancer is thyroidectomy followed by therapy with radioactive iodine and suppressive hormone therapy.