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

Abstract

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.

Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms

“…In contrast to the results of Pax8 and TTF-2 staining, our finding of TTF-1 expression in thyroid epithelial neoplasms is in keeping with reported results. 15,21,40 TTF-2 was not expressed in the non-thyroid normal tissues and tumors tested, whereas Pax8 was expressed in B lymphocytes, the renal tubule, epithelial cells of the fallopian tube and ovarian surface inclusion cyst, and tumors of metanephric and gonadal derivation, such as clear renal cell carcinomas, ovarian carcinomas, and seminomas. The latter findings are in keeping with those reported previously.…”

“…Indeed, TTF-1 is positive in 75% of lung adenocarcinomas, 14 and almost all cases of well-differentiated thyroid neoplasms of follicular origin. 15 Thorough routine microscopic examination, along with adequate clinical and radiographic information, generally would allow a definitive diagnosis in such a setting. Immunohistochemistry study can further solidify the diagnosis.…”

Overexpression of leucocyte common antigen (LAR) P-subunit in thyroid carcinomas

“…Studies demonstrated the positivities of galectin-3 in 100% of papillary carcinomas, 90 -100% of follicular carcinomas, 50 -80% of medullary carcinomas, 0 -33% of follicular adenomas and 0 -38% of nodular goitres (Beesley et al, 2002). Thyroid transcription factor-1 also expressed 100% of differentiated follicular tumours including follicular adenoma, follicular carcinoma and papillary carcinoma, but only 25% of undifferentiated carcinoma of the thyroid (Katoh et al, 2000). These markers were often expressed in benign lesions as well as malignant lesions, being due to the different mechanisms from LAR P-subunit.…”

Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin

“…Carcinomas arising from lung and thyroid also show frequent TTF-1 expression. 1,2 As the lung is one of the most common sites of metastasis, TTF-1 is considered as a reliable marker to distinguish between primary lung carcinoma and lung metastasis, especially when dealing with an adenocarcinoma or a large-cell carcinoma. [3][4][5][6] It is also considered as a reliable marker in the differential diagnosis between pleural localization of lung origin carcinoma and malignant mesothelioma.…”