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


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.
Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.|Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland.
Ari
A
Pelli
Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.|Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland.
Juha P
JP
Väyrynen
Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu, Oulu, Finland.|Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland.
Kai
K
Klintrup
Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu, Oulu, Finland.|Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland.
Jyrki
J
Mäkelä
Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.|Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland.
Markus J
MJ
Mäkinen
Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.|Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland.
Anne
A
Tuomisto
Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland. tuomo.karttunen@oulu.fi.|Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland. tuomo.karttunen@oulu.fi.
Tuomo J
TJ
Karttunen
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins
colorectal cancer; gremlin1; immunohistochemistry; prognosis; serrated adenocarcinoma