title: Mismatch repair deficiency as a prognostic factor in mucinous colorectal cancer.
abstract: There is some uncertainty about pathological grading of mucinous colorectal adenocarcinoma, defined as colorectal cancer demonstrating at least 50% mucinous differentiation. Under the WHO 2000 classification mucinous colorectal cancer was considered high grade. However under the current WHO 2010 classification microsatellite unstable/mismatch repair-deficient (MSI/MMRd) mucinous colorectal cancer is considered low grade, whereas microsatellite stable/mismatch repair proficient (MSS/MMRp) tumours are high grade. However there is little empirical evidence for this approach. We therefore compared the long term survival of patients with MSI/MMRd vs MSS/MMRp mucinous colorectal cancer in a large unselected cohort of patients undergoing surgery at our institution from 1998 to 2011. There were 2608 patients in the cohort, of which 264 (10.1%) were mucinous. 95 (36%) of the mucinous tumours were microsatellite unstable. The all-cause 5-year survival of mucinous MSI/MMRd colorectal cancer was similar to that of non-mucinous low-grade colorectal cancer (73 vs 67%, P=0.368), and significantly better than that of both non-mucinous high-grade (73 vs 53%, P<0.001) and mucinous MSS/MMRp colorectal cancer (73 vs 57%, P=0.023). The 5-year survival of mucinous MSS/MMRp colorectal cancer was slightly better than that of non-mucinous high-grade patients (57 vs 53%, P=0.027), but significantly worse than that of non-mucinous low-grade colorectal cancer (57 vs 67%, P=0.018). In multivariate Cox regression analysis, conventional histological grade based on glandular differentiation maintained prognostic significance (P=0.003) whereas MSI/MMRd status just failed to be statistically significant (P=0.062). Our findings support the WHO 2010 approach that as a group mucinous MSS/MMRp colorectal cancers are biologically aggressive. However, grading based exclusively on MSI/MMR status may be overly simplistic as conventional grading based on the degree of glandular differentiation still holds greater prognostic significance in multivariate analysis.
authors.affiliation: Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia.|Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: Juliana
authors.initials: J
authors.lastname: Andrici
authors.affiliation: Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia.|Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: Mahtab
authors.initials: M
authors.lastname: Farzin
authors.affiliation: Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia.|Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: Loretta
authors.initials: L
authors.lastname: Sioson
authors.affiliation: Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia.|Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: Adele
authors.initials: A
authors.lastname: Clarkson
authors.affiliation: Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Watson
authors.affiliation: Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia.|Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|Histopath Pathology, North Ryde, NSW, Australia.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Toon
authors.affiliation: Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia.|Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia.|Sydney Vital Translational Research Centre, Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gill
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000145:classification / Q000401:mortality / Q000473:pathology*; D000368:Aged; D015179:Colorectal Neoplasms / Q000145:classification / Q000401:mortality / Q000473:pathology*; D049914:DNA Repair-Deficiency Disorders / Q000401:mortality*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D060787:Neoplasm Grading / Q000379:methods*; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D046888:Tissue Array Analysis