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Clinicopathological and molecular implications of aberrant thyroid transcription factor-1 expression in colorectal carcinomas: an immunohistochemical analysis of 1319 cases using three different antibody clones.

Clinicopathological and molecular implications of aberrant thyroid transcription factor-1 expression in colorectal carcinomas: an immunohistochemical analysis of 1319 cases using three different antibody clones.
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Bae JM, Kim JH, Park JH, Park HE, Cho NY, Kang GH,


Bae JM, Kim JH, Park JH, Park HE, Cho NY, Kang GH, (click to view)

Bae JM, Kim JH, Park JH, Park HE, Cho NY, Kang GH,

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Histopathology 2017 12 0472(3) 423-432 doi 10.1111/his.13398

Abstract
AIMS
The precise profile of aberrant expression of thyroid transcription factor-1 (TTF-1) according to antibody clones in colorectal carcinomas (CRCs) has been controversial. Moreover, the detailed clinicopathological and molecular features of CRCs with TTF-1 expression have rarely been investigated. The aim of this study was to evaluate TTF-1 expression status in a large series of CRC cases by using three different antibody clones.

METHODS AND RESULTS
Immunohistochemistry for TTF-1 with clones 8G7G3/1, SPT24 and SP141 was performed on tumour tissues of 1319 primary CRCs and 98 corresponding metastatic lesions. Among the 1319 CRCs, TTF-1 expression was detected in 68 cases by both clone SPT24 and clone SP141. TTF-1 expression was not detected in any of the cases when clone 8G7G3/1 was used. The 68 CRCs with TTF-1 expression detected by both clone SPT24 and clone SP141 were considered to be TTF-1-positive in this study. TTF-1 positivity was significantly associated with distal tumour location, non-mucinous histology, intact CDX2 expression and a low frequency of KRAS mutations in CRCs. Nearly all TTF-1-positive CRCs showed microsatellite-stable and CpG island methylator phenotype-negative statuses. TTF-1 positivity was also found in all metastatic lesions of the five TTF-1-positive primary CRCs. TTF-1 negativity was maintained in all metastatic lesions of the 93 TTF-1-negative primary CRCs.

CONCLUSIONS
Our study confirmed that the frequency and characteristics of aberrant TTF-1 expression in CRCs vary according to the antibody clone. Aberrant TTF-1 expression detected by clone SPT24 or SP141 may be encountered preferentially in distally located, conventional pathway-type CRCs.

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