Thyroid Transcription Factor-1 in Normal, Hyperplastic, and Neoplastic Follicular Thyroid Cells Examined by Immunohistochemistry and Nonradioactive In Situ Hybridization

Department of Pathology, Yamanashi Medical University School of Medicine, Tamaho, Japan.
Modern Pathology (Impact Factor: 6.19). 06/2000; 13(5):570-6. DOI: 10.1038/modpathol.3880098
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Thyroid transcription factor-1 (TTF-1) has been known to regulate the transcriptional activity of thyroid-specific genes. We examined the expression of TTF-1 in non-neoplastic and neoplastic thyroid tissues. By immunohistochemistry, the nuclei of normal and hyperplastic follicular cells strongly reacted with the antibody against TTF-1. Immunohistochemistry also revealed a distinctive nuclear positivity of TTF-1 in all 33 differentiated follicular cell tumors, including 15 follicular adenomas, 5 follicular carcinomas, and 13 papillary carcinomas. No immunoreactions were observed in three of four undifferentiated carcinomas, whereas an isolated and weak nuclear positivity was obtained in one. In normal and hyperplastic tissues, the distribution of TTF-1 was fairly related to that of thyroid-specific proteins thyroglobulin and thyroperoxidase. However, discrepancies in the distribution were observed in tumor tissues. By in situ hybridization, the riboprobe hybridized distinctively with the cytoplasm of neoplastic cells as well as normal follicular cells. Papillary carcinoma cells expressed TTF-1 mRNA in all but two cases, and its expression was also demonstrated in one of four undifferentiated carcinomas. Reverse transcription-polymerase chain reaction confirmed the presence of TTF-1 mRNA in two human undifferentiated carcinoma cell lines, TTA-1 and TTA-2. In conclusion, the investigation of TTF-1 provides useful information on the functional activities and/or differentiation of thyroid tumors and may lead to an increase in our understanding of the biologic nature of thyroid tumors.

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Available from: Koichi Suzuki, Apr 02, 2014
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    • "Several immunohistochemical stains have been investigated for their possible role as diagnostic markers for PTC. They are cytokeratin19 (CK19), HBME1, galectin-3 and RET and thyroid transcription factor 1.[4–9] Although galectin-3 was initially shown to have utility in the differential diagnosis between benign and malignant thyroid lesions,[1011] recent studies suggest that it is not reliable.[12–14] Several studies have shown conflicting results regarding the usefulness of CK19 as a diagnostic marker in PTC.[13–20] "
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    ABSTRACT: The diagnosis of papillary thyroid carcinoma (PTC) is based on nuclear features. These features may be present in focal areas in benign thyroid diseases and follicular adenoma (FA), leading to diagnostic difficulty. To evaluate the expression and pattern of the distribution of cytokeratin 19 (CK19) in PTC and compare its reactivity with other neoplastic and non-neoplastic conditions to assess its potential as a useful marker for PTC. Twenty two cases of papillary carcinoma (usual type, follicular and diffuse sclerosing variant), eight follicular adenomas, eight multinodular goiters (MNG) were collected for a period of two years and six months. Sections were taken from thyroidectomy specimens fixed in 10% buffered neutral formalin. Hematoxylin and eosin staining and immunohistochemical staining for CK19 were done using standard protocol. Results were semiquantitatively scored as follows: 1+ (<5% positively stained cells), 2+ (5-25%), 3+ (25-75%) and 4+ (>75%), and then analyzed. STATISTICAL ANALYSIS AND RESULTS: All 22 (100%) papillary carcinomas showed diffuse and strong (3+ and 4+) CK19 expression. Six out of eight (75%) FAs and four out of eight (50%) MNG were positive for CK19, but it was of weaker intensity (1+ and 2+) and focal in distribution. Focal CK19 staining may be found in benign disease, but diffuse and strong positivity is characteristic of PTC, which can be used in the diagnosis of PTC in lesions of equivocal morphological appearances.
    Indian journal of medical and paediatric oncology 04/2012; 33(2):107-11. DOI:10.4103/0971-5851.99746
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    • "The thyroid transcription factor 1 (TTF-1) is a protein belonging to the homeobox-containing gene family. This kind of protein plays very important roles in development, cell growth and differentiation processes [1]. TTF-1 is required for expression of the thyroid stimulating hormone receptor gene in thyroid cells and essential for the morphogenesis of the thyroid, lung and ventral forebrain [2]. "
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    ABSTRACT: We report the immunohistochemical diagnosis, including TTF-1 (thyroid transcription factor 1) and Ki-67, of a rare mixed thyroid neoplasm composed of minimally invasive well differentiated follicular areas and highly aggressive undifferentiated anaplastic areas. A 75 old female presented to our clinic with a rapidly growing neck mass. Considering the dynamics of the disease and the multiple challenges presented by the patient: advanced age, tumor size, history of a longstanding goiter we decided to transfer her to the department of surgery. The intraoperative findings were an enlarged right lobe with tracheal and surrounding tissues infiltration. Total thyroidectomy, radical neck lymph nodes dissection and tracheostomy were performed. The histopathological and immunohistochemical examination revealed a coexistent anaplastic and follicular thyroid carcinoma. The proliferation index Ki-67, a cell proliferation marker, was found to be significantly higher in the anaplastic areas (30 +/- 5%) in the comparison with the follicular areas (2 +/- 1%). The evaluation of the thyroid transcription factor 1 (TTF-1) expression revealed a correlation with the tumor cells aggressiveness accordingly to the cancer areas. After a radical surgery an external adjuvant radiation was applied. The patient is alive and more than five years after diagnosis she presented an increase of the serum thyroglobulin level suggesting, probably, a recurrence of the follicular form of the cancer. According to our survey we suggest that in thyroid cancers TTF-1 and Ki-67 could provides useful information on the differentiation activities of thyroid tumor cells and may be helpful to distinguish well differentiated and undifferentiated areas in a mixed thyroid cancer.
    Folia Histochemica et Cytobiologica 02/2008; 46(4):461-4. DOI:10.2478/v10042-008-0071-y · 1.36 Impact Factor
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    • "All of the well-differentiated thyroid cancers such as the follicular and papillary carcinomas showed strong diffuse positivity, but in the poorly-differentiated carcinomas, the positivity reactivity was diminished and the most part of undifferentiated carcinomas showed a complete loss of immunoreactivity. These findings share similar characteristics to the studies with thyroglobulin, and this molecule can be interpreted as a marker of differentiation for thyroid carcinomas (23). "
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    ABSTRACT: To examine the immunohistochemical alterations associated with the histological dedifferentiation of thyroid carcinomas, we performed staining for HBME-1, high molecular weight cytokeratin (HCK), CK 19, thyroid transcription factor-1 (TTF-1) and E-cadherin (E-CD) on 125 various types of thyroid carcinomas. The HBME-1 staining was strong and diffuse in follicular carcinoma (FC), papillary carcinoma (PC), and poorly differentiated carcinoma (PDC), while it was rare in undifferentiated carcinoma (UC) as well as in benign lesions. Strong, diffuse staining for CK19 and HCK was predominantly found in PC, and these markers were not much found in other carcinomas. TTF-1 uniformly stained the tumor cells of all cases of PC, FC and Hurthle cell carcinoma (HC) and 42% of the PDC, while there was only focal staining in one case of the UC. Compared to the strong, diffuse reactivity in the benign lesions, E-CD staining was noted in 67% of PC, 80% of FC, 83% of HC, 58% of PDC and none of the UC. These results suggest that HBME-1 may be a marker for well-differentiated carcinomas while CK19 and HCK are phenotypic markers for papillary carcinoma. The loss or reduced expression of TTF-1 and E-CD may be markers for dedifferentiation.
    Journal of Korean Medical Science 11/2005; 20(5):853-9. DOI:10.3346/jkms.2005.20.5.853 · 1.27 Impact Factor
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