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Comparison of metabolic ratios of urinary estrogens between benign and malignant thyroid tumors in postmenopausal women.

Moon JY, Lee EJ, Chung WY, Moon MH, Chung BC, Choi MH - BMC Clin Pathol (2013)

Bottom Line: Estrogen metabolism may be associated with the pathophysiological development of papillary thyroid carcinoma (PTC).In addition, reductive 17β-hydroxysteroid dehydrogenase (17β-HSD; estradiol/estrone or estriol/16α-OH-estrone) was present at significantly higher levels in subjects with stage III/IV malignant PTCs than in benign subjects (>3.5-fold difference; P < 0.002).Increased 16α-hydroxylation and/or a decreased 2-/16α-ratio, as well increased reductive 17β-HSD, with regard to estrogen metabolism could provide potential biomarkers.

View Article: PubMed Central - HTML - PubMed

Affiliation: Future Convergence Research Division, Korea Institute of Science and Technology, 39-1 Hawolkok-dong, Seoul 136-791, Korea. mh_choi@kist.re.kr.

ABSTRACT

Background: Estrogen metabolism may be associated with the pathophysiological development of papillary thyroid carcinoma (PTC).

Methods: To evaluate the differential estrogen metabolism between benign and malignant PTCs, estrogen profiling by gas chromatography-mass spectrometry was applied to urine samples from postmenopausal patients with 9 benign tumors and 18 malignant stage I and III/IV PTCs.

Results: The urinary concentration of 2-methoxyestradiol was significantly lower in the stage I malignant patients (3.5-fold; P < 0.025) than in the benign group. The metabolic ratios of 16α-OH-estrone/estrone and estriol/estradiol, which are responsible for 16α-hydroxylase activity, were increased more than 2.5-fold in the advanced-stage malignant PTC (P < 0.02 each). The more than 6.2-fold decrease in the urinary 2-/16α-hydroxylase ratio in stage III/IV malignant PTC was consistent with the ratio in postmenopausal patients with endocrine gland cancers. In addition, reductive 17β-hydroxysteroid dehydrogenase (17β-HSD; estradiol/estrone or estriol/16α-OH-estrone) was present at significantly higher levels in subjects with stage III/IV malignant PTCs than in benign subjects (>3.5-fold difference; P < 0.002). In particular, the estriol/16α-OH-estrone ratio differentiated between the benign and early-stage malignant patients (P < 0.01).

Conclusions: Increased 16α-hydroxylation and/or a decreased 2-/16α-ratio, as well increased reductive 17β-HSD, with regard to estrogen metabolism could provide potential biomarkers. The devised profiles could be useful for differentiating malignant thyroid carcinomas from benign adenomas in postmenopausal women.

No MeSH data available.


Related in: MedlinePlus

Differential metabolic ratios on estrogen metabolism with statistical significance in benign and malignant papillary thyroid tumors. Estrogen activities were compared in postmenopausal women with benign adenomas (n = 9) and stage I (n = 11) and III/IV (n = 7) malignant carcinomas. The significant metabolic ratios with P < 0.05 in a Kruskal-Wallis test were analyzed with the Mann–Whitney U test between 2 groups, including benign versus stage I PTC, benign versus stage III/IV PTC, and stage I versus stage III/IV PTC. (A) 16α-OH-E1/E1, (B) E3/E2, (C) E2/E1, (D) E3/16α-OH-E1 and (E) 2-OH-E2/E3. * P < 0.02; ** P < 0.002; and *** P < 0.0002.
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Figure 1: Differential metabolic ratios on estrogen metabolism with statistical significance in benign and malignant papillary thyroid tumors. Estrogen activities were compared in postmenopausal women with benign adenomas (n = 9) and stage I (n = 11) and III/IV (n = 7) malignant carcinomas. The significant metabolic ratios with P < 0.05 in a Kruskal-Wallis test were analyzed with the Mann–Whitney U test between 2 groups, including benign versus stage I PTC, benign versus stage III/IV PTC, and stage I versus stage III/IV PTC. (A) 16α-OH-E1/E1, (B) E3/E2, (C) E2/E1, (D) E3/16α-OH-E1 and (E) 2-OH-E2/E3. * P < 0.02; ** P < 0.002; and *** P < 0.0002.

Mentions: Based on the individual concentrations, the metabolite to precursor ratios, which could be used to gain insight into metabolic enzyme activity, were examined to understand the alterations to estrogen metabolism with respect to thyroid tumors (Table 2). In contrast to the individual concentrations, significant changes between the patients with benign tumors and those with malignant PTCs, with either stage I or III/IV diagnosis, were confirmed by the differences in these metabolic ratios. For 16α-hydroxylase, the ratios of 16α-OH-E1 to E1 (Figure 1A) and E3 to E2 (Figure 1B) were significantly higher in patients with stage III/IV malignant PTCs than in those with benign tumors (P < 0.02 each). There were no significant changes in the metabolic activity of 4-hydroxylase of estrogens and catechol-O-methyltransferase of 2 and 4-hydroxy estrogens.


Comparison of metabolic ratios of urinary estrogens between benign and malignant thyroid tumors in postmenopausal women.

Moon JY, Lee EJ, Chung WY, Moon MH, Chung BC, Choi MH - BMC Clin Pathol (2013)

Differential metabolic ratios on estrogen metabolism with statistical significance in benign and malignant papillary thyroid tumors. Estrogen activities were compared in postmenopausal women with benign adenomas (n = 9) and stage I (n = 11) and III/IV (n = 7) malignant carcinomas. The significant metabolic ratios with P < 0.05 in a Kruskal-Wallis test were analyzed with the Mann–Whitney U test between 2 groups, including benign versus stage I PTC, benign versus stage III/IV PTC, and stage I versus stage III/IV PTC. (A) 16α-OH-E1/E1, (B) E3/E2, (C) E2/E1, (D) E3/16α-OH-E1 and (E) 2-OH-E2/E3. * P < 0.02; ** P < 0.002; and *** P < 0.0002.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016477&req=5

Figure 1: Differential metabolic ratios on estrogen metabolism with statistical significance in benign and malignant papillary thyroid tumors. Estrogen activities were compared in postmenopausal women with benign adenomas (n = 9) and stage I (n = 11) and III/IV (n = 7) malignant carcinomas. The significant metabolic ratios with P < 0.05 in a Kruskal-Wallis test were analyzed with the Mann–Whitney U test between 2 groups, including benign versus stage I PTC, benign versus stage III/IV PTC, and stage I versus stage III/IV PTC. (A) 16α-OH-E1/E1, (B) E3/E2, (C) E2/E1, (D) E3/16α-OH-E1 and (E) 2-OH-E2/E3. * P < 0.02; ** P < 0.002; and *** P < 0.0002.
Mentions: Based on the individual concentrations, the metabolite to precursor ratios, which could be used to gain insight into metabolic enzyme activity, were examined to understand the alterations to estrogen metabolism with respect to thyroid tumors (Table 2). In contrast to the individual concentrations, significant changes between the patients with benign tumors and those with malignant PTCs, with either stage I or III/IV diagnosis, were confirmed by the differences in these metabolic ratios. For 16α-hydroxylase, the ratios of 16α-OH-E1 to E1 (Figure 1A) and E3 to E2 (Figure 1B) were significantly higher in patients with stage III/IV malignant PTCs than in those with benign tumors (P < 0.02 each). There were no significant changes in the metabolic activity of 4-hydroxylase of estrogens and catechol-O-methyltransferase of 2 and 4-hydroxy estrogens.

Bottom Line: Estrogen metabolism may be associated with the pathophysiological development of papillary thyroid carcinoma (PTC).In addition, reductive 17β-hydroxysteroid dehydrogenase (17β-HSD; estradiol/estrone or estriol/16α-OH-estrone) was present at significantly higher levels in subjects with stage III/IV malignant PTCs than in benign subjects (>3.5-fold difference; P < 0.002).Increased 16α-hydroxylation and/or a decreased 2-/16α-ratio, as well increased reductive 17β-HSD, with regard to estrogen metabolism could provide potential biomarkers.

View Article: PubMed Central - HTML - PubMed

Affiliation: Future Convergence Research Division, Korea Institute of Science and Technology, 39-1 Hawolkok-dong, Seoul 136-791, Korea. mh_choi@kist.re.kr.

ABSTRACT

Background: Estrogen metabolism may be associated with the pathophysiological development of papillary thyroid carcinoma (PTC).

Methods: To evaluate the differential estrogen metabolism between benign and malignant PTCs, estrogen profiling by gas chromatography-mass spectrometry was applied to urine samples from postmenopausal patients with 9 benign tumors and 18 malignant stage I and III/IV PTCs.

Results: The urinary concentration of 2-methoxyestradiol was significantly lower in the stage I malignant patients (3.5-fold; P < 0.025) than in the benign group. The metabolic ratios of 16α-OH-estrone/estrone and estriol/estradiol, which are responsible for 16α-hydroxylase activity, were increased more than 2.5-fold in the advanced-stage malignant PTC (P < 0.02 each). The more than 6.2-fold decrease in the urinary 2-/16α-hydroxylase ratio in stage III/IV malignant PTC was consistent with the ratio in postmenopausal patients with endocrine gland cancers. In addition, reductive 17β-hydroxysteroid dehydrogenase (17β-HSD; estradiol/estrone or estriol/16α-OH-estrone) was present at significantly higher levels in subjects with stage III/IV malignant PTCs than in benign subjects (>3.5-fold difference; P < 0.002). In particular, the estriol/16α-OH-estrone ratio differentiated between the benign and early-stage malignant patients (P < 0.01).

Conclusions: Increased 16α-hydroxylation and/or a decreased 2-/16α-ratio, as well increased reductive 17β-HSD, with regard to estrogen metabolism could provide potential biomarkers. The devised profiles could be useful for differentiating malignant thyroid carcinomas from benign adenomas in postmenopausal women.

No MeSH data available.


Related in: MedlinePlus