Clinicopathological and molecular implications of aberrant TTF-1 expression in colorectal carcinomas: An immunohistochemical analysis of 1,319 cases using three different antibody clones

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. Here, we evaluated the TTF-1 expression status in a large series of CRC cases using three different antibody clones.

Methods and Results

Immunohistochemistry for TTF-1 using clones 8G7G3/1, SPT24, and SP141 was performed on tumour tissues of 1,319 primary CRCs and 98 corresponding metastatic lesions. Among the 1,319 CRCs, TTF-1 expression was detected in 68 cases using both clones SPT24 and 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 using both the SPT24 and SP141 clones were considered TTF-1-positive in this study. TTF-1 positivity was significantly associated with distal tumour location, non-mucinous histology, intact CDX2 expression, and 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 depending on 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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