Gremlin1 expression associates with serrated pathway and favourable prognosis in colorectal cancer.

AIMS

Gremlin1 is a bone morphogenetic protein (BMP) antagonist with a suggested role in colorectal cancer (CRC) progression. We have analysed Gremlin1 protein expression in CRC and assessed its correlation with clinicopathological characteristics, including developmental pathway and prognosis.

METHODS AND RESULTS

Material included a non-selected series of 148 surgically treated CRC cases. The tumour-node-metastasis (TNM) stage, histological grade and inflammatory infiltrate at the invasive margin were assessed, and tumours were classified to serrated or non-serrated types. Immunohistochemistry was conducted to evaluate Gremlin1 expression. Prognosis (60-month follow-up) was analysed by Kaplan-Meier methods and Cox regression analysis. Gremlin1 expression was detected in epithelial cells both in normal mucosa and in carcinomas. Abundant expression in carcinomas associated with low TNM stage (P = 0.044), low histological grade (P = 0.044), serrated histology (P = 0.033 or P = 0.053 depending on the classification cut-off) and intensive inflammatory infiltrate at the invasive margin (P = 0.044), and was a stage independent indicator of extended survival (P = 0.029).

CONCLUSIONS

Gremlin1 protein expression in CRC associates with low tumour stage and extended survival independently of tumour stage, suggesting that it represents a relevant prognostic indicator in CRC. High expression in carcinomas with serrated histology suggests a potential role for Gremlin1 in the serrated pathway of CRC.