TY - JOUR
T1 - Associations of non-pedunculated T1 colorectal adenocarcinoma outcome with consensus molecular subtypes, immunoscore, and microsatellite status
T2 - a multicenter case-cohort study
AU - Haasnoot, Krijn J.C.
AU - Backes, Yara
AU - Moons, Leon M.G.
AU - Kranenburg, Onno
AU - Trinh, Anne
AU - Vermeulen, Louis
AU - Noë, Michaël
AU - Tuynman, Jurriaan B.
AU - van Lent, Anja U.G.
AU - van Ginneken, Rosaline
AU - Seldenrijk, Cornelis A.
AU - Raicu, Mihaela G.
AU - Trumpi, Kari
AU - Ubink, Inge
AU - Milne, Anya N.
AU - Boonstra, Jurjen J.
AU - Groen, John N.
AU - Schwartz, Matthijs P.
AU - Wolfhagen, Frank H.J.
AU - Geesing, Joost M.J.
AU - ter Borg, Frank
AU - Brosens, Lodewijk A.A.
AU - van Bergeijk, Jeroen
AU - Spanier, Bernhard W.M.
AU - de Vos tot Nederveen Cappel, Wouter H.
AU - Kessels, Koen
AU - Seerden, Tom C.J.
AU - Vleggaar, Frank P.
AU - Offerhaus, G. Johan A.
AU - Siersema, Peter D.
AU - Elias, Sjoerd G.
AU - Laclé, Miangela M.
N1 - Funding Information:
Funding This investigator-initiated study was supported by a grant from the Dutch Digestive Diseases Foundation (reference MG/2015-040). This study was performed and written independently of the funder.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Advanced colorectal cancer (CRC) consensus molecular subtype 4 (CMS4) or CRC with a low immunoscore is associated with shorter survival times. Non-metastatic CRC with microsatellite instability (MSI) is associated with a lower risk of recurrence. We evaluated outcome (lymph node metastases [LNM] or cancer recurrence) in these tumor subtypes in patients with surgically-removed non-pedunculated T1 CRC by performing a multicenter case-cohort study. We included all patients in 13 hospitals in the Netherlands from 2000–2014 (n = 651). We randomly selected a subgroup of patients (n = 223) and all patients with LNM or recurrence (n = 63), and median follow-up of 44 months. We centrally reviewed tumor-slides, and constructed and immunostained tissue microarrays determining MSI, CMS (MSI/CMS1, CMS2/3, or CMS4), and immunoscore (I-low/I-high). We used weighted Cox proportional hazard models to evaluate the association of MSI, CMS, and immunoscore with LNM or recurrence, adjusting for conventional histologic risk factors. In the randomly selected subgroup of patients, 7.1% of tumors were MSI/CMS1, 91.0% CMS2/3, 1.8% CMS4, and 25% I-low. In the case-cohort, patients with CMS4 tumors had an increased risk for LNM or recurrence compared with patients with tumors of other CMSs (adjusted hazard ratio [HR], 3.97; 95% CI, 1.12–14.06; P = 0.03). Albeit not significant, tumors with MSI had a lower risk for LNM or recurrence than other tumor subtypes (adjusted HR, 0.52; 95% CI, 0.12–2.30; P = 0.39), whereas tumors with a low immunoscore had an increased risk for LNM or recurrence (adjusted HR, 1.30; 95% CI, 0.68–2.48; P = 0.43). In conclusion, in a case-cohort study of patients with non-pedunculated T1 CRC, MSI, and immunoscore were not significantly associated with adverse outcome after surgery. CMS4 substantially increased the risk of adverse outcome. However, CMS4 is rare in T1 CRCs, limiting its value for determining the risk in patients.
AB - Advanced colorectal cancer (CRC) consensus molecular subtype 4 (CMS4) or CRC with a low immunoscore is associated with shorter survival times. Non-metastatic CRC with microsatellite instability (MSI) is associated with a lower risk of recurrence. We evaluated outcome (lymph node metastases [LNM] or cancer recurrence) in these tumor subtypes in patients with surgically-removed non-pedunculated T1 CRC by performing a multicenter case-cohort study. We included all patients in 13 hospitals in the Netherlands from 2000–2014 (n = 651). We randomly selected a subgroup of patients (n = 223) and all patients with LNM or recurrence (n = 63), and median follow-up of 44 months. We centrally reviewed tumor-slides, and constructed and immunostained tissue microarrays determining MSI, CMS (MSI/CMS1, CMS2/3, or CMS4), and immunoscore (I-low/I-high). We used weighted Cox proportional hazard models to evaluate the association of MSI, CMS, and immunoscore with LNM or recurrence, adjusting for conventional histologic risk factors. In the randomly selected subgroup of patients, 7.1% of tumors were MSI/CMS1, 91.0% CMS2/3, 1.8% CMS4, and 25% I-low. In the case-cohort, patients with CMS4 tumors had an increased risk for LNM or recurrence compared with patients with tumors of other CMSs (adjusted hazard ratio [HR], 3.97; 95% CI, 1.12–14.06; P = 0.03). Albeit not significant, tumors with MSI had a lower risk for LNM or recurrence than other tumor subtypes (adjusted HR, 0.52; 95% CI, 0.12–2.30; P = 0.39), whereas tumors with a low immunoscore had an increased risk for LNM or recurrence (adjusted HR, 1.30; 95% CI, 0.68–2.48; P = 0.43). In conclusion, in a case-cohort study of patients with non-pedunculated T1 CRC, MSI, and immunoscore were not significantly associated with adverse outcome after surgery. CMS4 substantially increased the risk of adverse outcome. However, CMS4 is rare in T1 CRCs, limiting its value for determining the risk in patients.
UR - http://www.scopus.com/inward/record.url?scp=85086785830&partnerID=8YFLogxK
U2 - 10.1038/s41379-020-0598-9
DO - 10.1038/s41379-020-0598-9
M3 - Article
AN - SCOPUS:85086785830
SN - 0893-3952
VL - 33
SP - 2626
EP - 2636
JO - Modern Pathology
JF - Modern Pathology
IS - 12
ER -