Sex-steroid hormone receptors in human medullary thyroid carcinoma

Department of Endocrinology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Modern Pathology (Impact Factor: 6.19). 02/1996; 9(1):68-72.
Source: PubMed


Three complementary techniques were used to detect sex-steroid hormone receptors in tumor tissues from seven patients with medullary thyroid carcinoma: steroid binding analysis, enzyme immune assay, and immunohistochemistry. The presence of estrogen receptors was detected by steroid binding analysis in one of seven patients, although in very low concentrations (3.17 to 5.06 fmol/mg protein). These results were confirmed by enzyme immune assay (6.35 to 9.32 fmol/mg protein). Progesterone receptors were found in five of seven patients by steroid binding analysis (11.1 to 47.9 fmol/mg protein), and progesterone receptor results were confirmed by enzyme immune assay (8.1 to 34.1 fmol/mg protein). By immunohistochemistry, progesterone receptors were focally detected in all cases, whereas all tumors were negative for estrogen receptors. In summary, our results confirm the presence of sex-steroid hormone receptors, particularly progesterone receptors in medullary thyroid carcinoma. The presence of progesterone receptors in medullary thyroid carcinoma apparently does not require the continuous presence of estrogen receptors.

2 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Medullary thyroid carcinoma (MTC) is an uncommon tumour of calcitonin-secreting C-cells of the thyroid gland. This cancer represents an important potential model for the study of mechanisms of human epithelial cell transformation. Although recent studies have identified the gene involved in familial forms of MTC, little is known about the molecular pathogenesis of the sporadic variants of this tumour. The biological and prognostic significance of TFF1 expression, particularly in diverse human malignancies, suggests that the TFF1 protein could have a role in human neoplasia. Furthermore, in prostate cancer it has been demonstrated that TFF1 expression is closely associated with premalignant changes and neuroendocrine differentiation. In the present study, the expression of TFF1 was analysed in 18 human MTCs, comprising sporadic and familial tumours, C-cell hyperplasia, and one case of lymph gland metastasis. TFF1 expression was also examined in the cultures of a human MTC-derived tumour cell line (TT cell line). The results showed that ten sporadic tumours, three hereditary tumours (including C-cell hyperplasia), and one lymph gland metastasis displayed TFF1 immunoreactivity. Indirect fluorescence immunocytochemistry and Western blotting revealed that the TFF1 protein was strongly expressed in the TT cells. Northern analysis revealed that tumours and TT cells expressed the TFF1 transcript. Although the function of TFF1 protein in the carcinogenesis of MTC remains to be elucidated, its expression in the majority of cases of both sporadic and hereditary tumours, metastatic tumours, and in C-cell hyperplasia suggests that it may contribute to the pathogenesis of MTC.
    The Journal of Pathology 04/1998; 184(4):408-13. DOI:10.1002/(SICI)1096-9896(199804)184:4<408::AID-PATH1222>3.0.CO;2-3 · 7.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The mechanism by which cortisol is produced in adrenal Cushing's syndrome, when ACTH is suppressed, was previously unknown and was referred to as being "autonomous." More recently, several investigators have shown that some cortisol and other steroid-producing adrenal tumors or hyperplasias are under the control of ectopic (or aberrant, illicit, inappropriate) membrane hormone receptors. These include ectopic receptors for gastric inhibitory polypeptide (GIP), beta-adrenergic agonists, or LH/hCG; a similar outcome can result from altered activity of eutopic receptors, such as those for vasopressin (V1-AVPR), serotonin (5-HT4), or possibly leptin. The presence of aberrant receptors places adrenal cells under stimulation by a trophic factor not negatively regulated by glucocorticoids, leading to increased steroidogenesis and possibly to the proliferative phenotype. The molecular mechanisms responsible for the abnormal expression and function of membrane hormone receptors are still largely unknown. Identification of the presence of these illicit receptors can eventually lead to new pharmacological therapies as alternatives to adrenalectomy, now demonstrated by the long-term control of ectopic P-AR- and LH/hCGR-dependent Cushing's syndrome by propanolol and leuprolide acetate. Further studies will potentially identify a larger diversity of hormone receptors capable of coupling to G proteins, adenylyl cyclase, and steroidogenesis in functional adrenal tumors and probably in other endocrine and nonendocrine tumors.
    Endocrine Reviews 03/2001; 22(1):75-110. DOI:10.1210/edrv.22.1.0420 · 21.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We have conducted a quantitative analysis of estrogen receptor-alpha (ER-alpha) and -beta (ER-beta) mRNA expression in normal thyroid and tumor tissues. Normal thyroid tissues (n = 10) and tumor tissues [(follicular adenoma (n = 14), follicular carcinoma (n = 8), papillary carcinoma (n = 14), anaplastic carcinoma (n = 3) and medullary carcinoma (n = 6)] were obtained at surgery from 45 female patients. ER-alpha and ER-beta mRNA expression has been studied by a quantitative polymerase chain reaction. ER-alpha mRNA levels in the normal thyroid were not significantly different from those in follicular adenomas, papillary carcinomas and medullary carcinomas but were marginally (p = 0.08) higher than those in follicular and anaplastic carcinomas. ER-beta mRNA levels in the normal thyroid tissues were not significantly different from those in any other tumor tissues. ER-beta to ER-alpha mRNA ratios were significantly (p < 0.05) higher in the normal thyroid tissues than in follicular adenomas. Proportions of ER-beta mRNA variants (ER-beta 1, 2, 5, and 5') did not significantly differ among the normal and tumor tissues. A downregulation of ER-alpha mRNA in follicular and anaplastic carcinomas seems to suggest that estrogens are unlikely to play an important role in the carcinogenesis and progression of these carcinomas. On the other hand, a significant decrease in ER-beta to ER-alpha mRNA ratios in follicular adenomas suggests a possible involvement of estrogens in the pathogenesis of this disease since the same phenomenon has been reported on estrogen-dependent breast cancers.
    Oncology 11/2001; 61(4):293-8. DOI:10.1159/000055336 · 2.42 Impact Factor
Show more