I S Reynolds1,2, S J Furney2, E W Kay3,4, D A McNamara1,5, J H M Prehn2, J P Burke1. 1. Department of Surgery, Beaumont Hospital, Dublin, Ireland. 2. Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland. 3. Department Pathology, Beaumont Hospital, Dublin, Ireland. 4. Department of Pathology, Royal College of Surgeons in Ireland, Dublin, Ireland. 5. Department of Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland.
Abstract
BACKGROUND: Mucinous differentiation occurs in 5-15 per cent of colorectal adenocarcinomas. This subtype of colorectal cancer responds poorly to chemoradiotherapy and has a worse prognosis. The genetic aetiology underpinning this cancer subtype lacks consensus. The aim of this study was to use meta-analytical techniques to clarify the molecular associations of mucinous colorectal cancer. METHODS: This study adhered to MOOSE guidelines. Databases were searched for studies comparing KRAS, BRAF, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), p53 and p27 status between patients with mucinous and non-mucinous colorectal adenocarcinoma. A random-effects model was used for analysis. RESULTS: Data from 46 studies describing 17 746 patients were included. Mucinous colorectal adenocarcinoma was associated positively with KRAS (odds ratio (OR) 1·46, 95 per cent c.i. 1·08 to 2·00, P = 0·014) and BRAF (OR 3·49, 2·50 to 4·87; P < 0·001) mutation, MSI (OR 3·98, 3·30 to 4·79; P < 0·001) and CIMP (OR 3·56, 2·85 to 4·43; P < 0·001), and negatively with altered p53 expression (OR 0·46, 0·31 to 0·67; P < 0·001). CONCLUSION: The genetic origins of mucinous colorectal adenocarcinoma are predominantly associated with BRAF, MSI and CIMP pathways. This pattern of molecular alterations may in part explain the resistance to standard chemotherapy regimens seen in mucinous adenocarcinoma.
BACKGROUND: Mucinous differentiation occurs in 5-15 per cent of colorectal adenocarcinomas. This subtype of colorectal cancer responds poorly to chemoradiotherapy and has a worse prognosis. The genetic aetiology underpinning this cancer subtype lacks consensus. The aim of this study was to use meta-analytical techniques to clarify the molecular associations of mucinous colorectal cancer. METHODS: This study adhered to MOOSE guidelines. Databases were searched for studies comparing KRAS, BRAF, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), p53 and p27 status between patients with mucinous and non-mucinous colorectal adenocarcinoma. A random-effects model was used for analysis. RESULTS: Data from 46 studies describing 17 746 patients were included. Mucinous colorectal adenocarcinoma was associated positively with KRAS (odds ratio (OR) 1·46, 95 per cent c.i. 1·08 to 2·00, P = 0·014) and BRAF (OR 3·49, 2·50 to 4·87; P < 0·001) mutation, MSI (OR 3·98, 3·30 to 4·79; P < 0·001) and CIMP (OR 3·56, 2·85 to 4·43; P < 0·001), and negatively with altered p53 expression (OR 0·46, 0·31 to 0·67; P < 0·001). CONCLUSION: The genetic origins of mucinous colorectal adenocarcinoma are predominantly associated with BRAF, MSI and CIMP pathways. This pattern of molecular alterations may in part explain the resistance to standard chemotherapy regimens seen in mucinous adenocarcinoma.
Authors: Ian S Reynolds; Valentina Thomas; Emer O'Connell; Michael Fichtner; Deborah A McNamara; Elaine W Kay; Jochen H M Prehn; John P Burke; Simon J Furney Journal: Front Oncol Date: 2020-08-26 Impact factor: 6.244
Authors: Ian S Reynolds; Paul M Cromwell; Éanna J Ryan; Erinn McGrath; Rory Kennelly; Ronan Ryan; Niall Swan; Kieran Sheahan; Des C Winter; Emir Hoti Journal: Front Oncol Date: 2022-02-21 Impact factor: 6.244
Authors: David S Williams; Dmitri Mouradov; Marsali R Newman; Elham Amini; David K Nickless; Catherine G Fang; Michelle Palmieri; Anuratha Sakthianandeswaren; Shan Li; Robyn L Ward; Nicholas J Hawkins; Iain Skinner; Ian Jones; Peter Gibbs; Oliver M Sieber Journal: Mod Pathol Date: 2020-02-11 Impact factor: 7.842