Increased expression of trefoil factor 3 (TFF3) has been reported in colorectal carcinoma (CRC), being correlated with distant metastasis and poor clinical outcomes.
In this study, the expression of TFF3 and the epithelial-mesenchymal transition (EMT) transcriptional factor Snail in PTC and para-carcinoma specimens was evaluated by immunohistochemistry (IHC) and Western blot, and the possible associations with lymph node (LN) metastasis and other clinicopathological parameters were analysed.
TFF3, which encodes for trefoil factor 3 and is an estrogen-responsive oncogene shown to play a functional role in tamoxifen resistance and metastasis of ER+ breast cancer, was also shown to be upregulated in an AI-resistant cell line model, and reduction of TFF3 levels using TFF3-specific siRNAs decreased the growth of both the AI-resistant and -sensitive parental cell lines.
There were two MCRs in common between the groups on 19q13 and 21q21, containing genes involved in resistance to anoikis, TGFβ-signaling and metastasis (TFF3, LTBP4, NUMBL).
In conclusion, TFF3 expression is associated with response to endocrine therapy, and outperforms oestrogen receptor, progesterone receptor and TFF1 as an independent biomarker, possibly because it mediates the malign effects of oestrogen on invasion and metastasis.
Furthermore, among 134 patients with no clinical findings of metastasis at surgery, the patients with positive TFF3 experienced recurrence within one year more frequently than those with negative TFF3 (p=0.039).
TFF3 expression predicts metastasis and poor survival outcome of patients with MC and functionally stimulates cellular invasion and metastasis of ER+ MC cells.
The results indicate that TFF3 point mutations seem to be a rare event in colorectal carcinogenesis; TFF3 expression may play a role in promoting lymph node metastases of CRCs and serum TFF3 may be a potential useful marker for patients with CRCs and their metastases.
These results indicate that the decreased expression of TFF3 mRNA is a marker of follicular carcinomas, especially those with a high risk of invasion or metastasis.