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.

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.