Mouse Anti-Human TTF-1 monoclonal antibody, clone JID525

Concept: Redifferentiation of thyroid carcinoma cells has the potential to increase the efficacy of radioactive iodine therapy in treatment-refractory, nonmedullary thyroid carcinoma (TC), leading to an improved disease outcome. Mammalian target of rapamycin (mTOR) is a key regulator of cell fate affecting survival and differentiation, with autophagy and inflammation as prominent downstream pathways. Methods: The effects of mTOR inhibition were studied for its redifferentiation potential of the human TC cell lines BC-PAP, FTC133, and TPC1 by assessment of mRNA and protein expression of thyroid-specific genes and by performance of iodine uptake assays. Results: In thyroid transcription factor 1 (TTF1)-expressing cell lines, mTOR inhibition promoted redifferentiation of TC cells by the up-regulation of human sodium-iodine symporter mRNA and protein expression. Furthermore, these cells exhibited markedly elevated iodine uptake capacity. Surprisingly, this redifferentiation process was not mediated by autophagy induced during mTOR inhibition or by inflammatory mediators but through transcriptional effects at the level of TTF1 expression. Accordingly, small interfering RNA inhibition of TTF1 completely abrogated the induction of human sodium-iodine symporter by mTOR inhibition. Conclusion: The present study has identified the TTF1-dependent molecular mechanisms through which the inhibition of mTOR leads to the redifferentiation of TC cells and subsequently to increased radioactive iodine uptake.

Although thyroid transcription factor-1 (TTF-1) immunoreactivity is considered as a specific marker of lung and thyroid neoplasms, it may be positive in a proportion of extrapulmonary adenocarcinomas. This study examined the expression of TTF-1 in 555 colorectal adenocarcinomas using three commercial monoclonal antibodies: clone SPT24 (Novocastra) and 8G7G3/1 (Dako and Cell Marque), and compared the TTF-1 staining with other immunohistochemical markers, cytokeratin (CM) 7, CK 20, caudal-type homeobox transcription factor 2 (CDX2), and MUC2. The clinicopathological prognostic factors were compared with the TTF-1 expression status. Nuclear TTF-1 staining was detected in 24 cases (4.3%) with the SPT24 antibody and 18 cases (3.2%) with the 8G7G3/1 antibody. All cases positive for 8G7G3/1 were also positive for SPT24. CDX2 was expressed constantly in all 24 TTF-1-positive colorectal cancers, whereas CK7, CK20, and MUC2 were detected in 2 (8.3%), 23 (95.8%), and 8 (33.3%) cases, respectively. There was no correlation between TTF-1 expression and clinicopathological significance. To avoid potential pitfalls, TTF-1 should be interpreted in conjunction with the clinical setting, histological features, and the results of other markers, such as CK7, CK20, and CDX2. MUC2 can be used as supplementary information to confirm difficult cases. (C) 2011 Elsevier GmbH. All rights reserved.