Published online Jul 14, 2017. doi: 10.3748/wjg.v23.i26.4831
Peer-review started: December 16, 2016
First decision: February 23, 2017
Revised: March 14, 2017
Accepted: May 19, 2017
Article in press: May 19, 2017
Published online: July 14, 2017
To characterize the expression of toll-like receptors (TLR) 2 and 4 in colorectal cancer (CRC) and in normal colorectal mucosa.
We analysed tissue samples from a prospective series of 118 unselected surgically treated patients with CRC. Sections from formalin fixed, paraffin embedded specimens were analysed for TLR2 and TLR4 expression by immunohistochemistry. Two independent assessors evaluated separately expression at the normal mucosa, at the invasive front and the bulk of the carcinoma, and in the lymph node metastases when present. Expression levels in different locations were compared and their associations with clinicopathological features including TNM-stage and the grade of the tumour and 5-year follow-up observations were analysed.
Normal colorectal epithelium showed a gradient of expression of both TLR2 and TLR4 with low levels in the crypt bases and high levels in the surface. In CRC, expression of both TLRs was present in all cases and in the major proportion of tumour cells. Compared to normal epithelium, TLR4 expression was significantly weaker but TLR2 expression stronger in carcinoma cells. Weak TLR4 expression in the invasive front was associated with distant metastases and worse cancer-specific survival at 5 years. In tumours of the proximal colon the cancer-specific survival at 5 years was 36.9% better with strong TLR4 expression as compared with those with weak expression (P = 0.044). In contrast, TLR2 expression levels were not associated with prognosis. Tumour cells in the lymph node metastases showed higher TLR4 expression and lower TLR2 expression than cells in primary tumours.
Tumour cells in CRC show downregulation of TLR4 and upregulation of TLR2. Low expression of TLR4 in the invasive front predicts poor prognosis and metastatic disease.
Core tip: Toll-like receptor 4 (TLR4) is downregulated in colorectal cancer (CRC), suggesting a role as a tumour suppressor. Low expression of TLR4 in the invasive front marks poor prognosis and is associated with metastatic disease. The most significant finding was the association between weak TLR4 expression in the tumour front and 36.9% (P = 0.044) lower cancer-specific survival in cancer of the proximal colon as compared with strong TLR4 expression. Weak TLR4 staining in tumour front was present in 50% (11/22) of the cases with metastases and only in 17% (16/94) of those without metastases (P = 0.001). TLR2 is upregulated in CRC but not associated with prognosis.