bromochloroacetic-acid and Goiter

Topics: Aged; Biomarkers, Tumor; Biopsy, Fine-Needle; Female; Goiter; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Melanoma

Topics: Biopsy, Needle; Calcitonin; Carcinoembryonic Antigen; Female; Goiter; Humans; Keratins; Middle Aged; Synaptophysin; Thyroglobulin; Thyroid Gland

Galectin-7 is associated with p53-dependent onset of apoptosis and proliferation control/differentiation in keratinocyte development. It is also up-regulated in chemically induced rat mammary carcinogenesis. Because the levels of expression of galectin-7 have never been investigated in thyroid tumors (in contrast to those of galectin-1 and -3 associated with malignancy), we initiated analysis of the expression of galectin-7 in benign and malignant thyroid lesions together with that of cytokeratin-19 (CK19), a marker already demonstrated to be useful in diagnosing this kind of lesion. The immunohistochemical expression levels were quantitatively determined by means of computer-assisted microscopy on a series of 84 thyroid lesions including 10 multinodular goiters, 32 adenomas, and 42 carcinomas. Our data clearly indicate a marked down-regulation of galectin-7 expression in a large proportion of adenomas (including the normomacrofollicular, microfollicular, and trabecular variants) if compared with carcinomas. In accordance with results of previous studies, a marked up-regulation of CK19 expression was observed in the thyroid carcinomas, and this contrasted in particular with the low CK19 expression observed in the microfollicular adenomas. Of importance for diagnostic implications, the combination of these two markers enabled our series of microfollicular adenomas (characterized by low galectin-7 and CK19 expression) to be efficiently distinguished from the encapsulated follicular variant of papillary thyroid carcinomas (high galectin-7 and CK19 expression).

Topics: Adenoma; Carcinoma; Disease Progression; Galectins; Goiter; Humans; Immunohistochemistry; Keratins; Thyroid Gland; Thyroid Neoplasms

Topics: Adenocarcinoma, Follicular; Adenoma; Carcinoma, Papillary; Diagnosis, Differential; Fluorescent Antibody Technique, Direct; Goiter; Humans; Immunohistochemistry; Keratins; Thyroid Neoplasms

Previous studies indicate that keratins 7, 8 and 18 are present in all thyroid papillary and follicular lesions, but the distribution of other keratins has been incompletely characterized. The profile of individual keratin (K) polypeptides was evaluated immunohistochemically in over 200 non-neoplastic and neoplastic thyroid papillary and follicular lesions. Monoclonal antibodies to K19, K17, K16, K5/6 and K10 were applied in paraffin sections of formaldehyde-fixed tissue. K19 was present variably, often only focally in goitres, and was present only sporadically in papillary hyperplasia. However, K19 was strongly and uniformly expressed in virtually all papillary carcinomas, indicating differential diagnostic usefulness in differentiating papillary hyperplasia and papillary carcinoma. About half of the follicular carcinomas (defined as tumours strictly excluding the follicular variant of papillary carcinoma) were also strongly K19-positive, suggesting that K19 patterns are not reliable in differentiating papillary and follicular carcinoma. K17 and K5/6 were present in cysts and squamous metaplasia of goitres, and focally in papillary but only exceptionally in follicular carcinoma in areas of squamous differentiation and tumour cells in desmoplastic stroma. K16 in turn was present only focally in well-developed squamous metaplasia in goitres but was not found in differentiated thyroid carcinomas. K10, a high-molecular-weight keratin typical of epidermal differentiation, was identified neither in non-neoplastic nor in neoplastic differentiated thyroid lesions, including squamous metaplasia. These results indicate that papillary carcinomas differ from other differentiated thyroid tumours in their varying, usually focal, expression of stratified epithelial keratins that are partly but not exclusively related to squamous differentiation in such lesions. However, papillary carcinomas do not express truly epidermally restricted keratins; their previously described reactivity with polyclonal "epidermal keratin" antibodies most probably results from the reactivity of such antibodies with K19.

Topics: Adenocarcinoma, Follicular; Adenoma; Carcinoma, Papillary; Diagnosis, Differential; Goiter; Humans; Immunohistochemistry; Keratins; Thyroid Neoplasms

While the multifunctional proteins of the transforming growth factor-beta (TGF-beta) family have a potent antiproliferative effect on thyroid follicular cell growth, increased expression of TGF-beta in proliferating thyroid cells and in thyroid tumours has recently been described, suggesting a secondary counter-regulatory role of these proteins. We have studied further this apparent paradox in vitro using FRTL-5 cells, 5 continuous cell strains from feline multinodular goitres (MNG) and 29 primary cultures prepared from human MNG. While dose dependent inhibition of FRTL-5 cell growth was confirmed, a variable fraction of these cells was naturally resistant towards TGF-beta 1, thus explaining the large interassay variability of growth inhibition (36 to 98% within 2 days, n = 19). After 40 days of continuous exposure, FRTL-5 cells became fully refractory towards TGF-beta 1 inhibition, due to the selective growth of naturally resistant subclones, as demonstrated for example by microscopic observation of three-dimensionally growing collagen-embedded cell clusters. The refractoriness could still be demonstrated even after several cell passages. In addition, 2 out of 5 feline thyroid cell strains obtained from feline MNG and 18 out of 29 primary cultures from human MNG showed a high degree of refractoriness towards TGF-beta. We conclude that constitutively TGF-beta resistant cells may occur in thyroid glands and that persistent TGF-beta refractoriness may secondarily be acquired. Resistant cells may escape regular growth control mechanisms and hence may contribute to the notorious heterogeneity of thyroid growth and to nodular transformation.

Topics: Animals; Cats; Cell Division; Cell Line; Clone Cells; Depression, Chemical; Dose-Response Relationship, Drug; Drug Resistance; Goiter; Humans; Immunohistochemistry; Keratins; Thyroglobulin; Thyroid Gland; Time Factors; Transforming Growth Factor beta; Tumor Cells, Cultured

We performed a comparative study using immunoperoxidase staining on 11 cases of thyroid micro cancer (TCM) and 7 cases of clinically manifested cancers (CMC). Antibodies against 4 kinds of cytoskeletal proteins and thyroglobulin were used. In the TCM and CMC groups, actin and myosin were identified in almost all neoplastic cells of all patients; keratin and vimentin were present in the tumor cells of several patients. Keratin was found only in papillary carcinoma cells. Thyroglobulin was present in the neoplastic cells of several patients from both groups; follicular carcinoma cells and keratin-negative cells reacted more strongly with thyroglobulin than papillary carcinoma cells or keratin-positive cells. There was no special difference between TMC and CMC in the localization of cytoskeletal proteins and thyroglobulin.

Topics: Adenoma; Adult; Aged; Desmin; Female; Glial Fibrillary Acidic Protein; Goiter; Humans; Intermediate Filament Proteins; Keratins; Middle Aged; Neoplasm Proteins; Thyroglobulin; Thyroid Neoplasms; Thyroiditis, Autoimmune; Vimentin