Journal Article

Associations of non-pedunculated T1 colorectal adenocarcinoma outcome with consensus molecular subtypes, immunoscore, and microsatellite status: a multicenter case-cohort study

Groen, John N., Haasnoot, Krijn J.C., Laclé, Miangela M., ter Borg, Frank, Offerhaus, G. Johan A., van Ginneken, Rosaline, Noë, Michaël, Geesing, Joost M.J., Schwartz, Matthijs P., Moons, Leon M.G., Trumpi, Kari, Vleggaar, Frank P., de Vos tot Nederveen Cappel, Wouter H., Brosens, Lodewijk A.A., Milne, Anya N., Seerden, Tom C.J., Tuynman, Jurriaan B., Seldenrijk, Cornelis A., Wolfhagen, Frank H.J., Vermeulen, Louis, Ubink, Inge, van Bergeijk, Jeroen, Spanier, Bernhard W.M., Kessels, Koen, Raicu, Mihaela G., Trinh, Anne, Kranenburg, Onno, Siersema, Peter D., van Lent, Anja U.G., Elias, Sjoerd G., Backes, Yara, Boonstra, Jurjen J.

2020

Overview

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.

• Publisher: Elsevier Inc,Nature Publishing Group US,Elsevier Limited
• Subject: 13/1 / 13/51 / 14/63 / 38/61 / 631/67/1504/1885 / 631/67/1857 / 692/53/2423 / Adenocarcinoma / Adenocarcinoma - chemistry / Adenocarcinoma - genetics / Adenocarcinoma - secondary / Adenocarcinoma - surgery / Aged / Biomarkers, Tumor - analysis / Case-Control Studies / Cohort analysis / Colorectal cancer / Colorectal carcinoma / Colorectal Neoplasms - chemistry / Colorectal Neoplasms - genetics / Colorectal Neoplasms - pathology / Colorectal Neoplasms - surgery / DNA Repair Enzymes - analysis / Female / Genetic Predisposition to Disease / Humans / Immunohistochemistry / Laboratory Medicine / Lymph nodes / Male / Medicine / Medicine & Public Health / Metastases / Microsatellite Instability / Middle Aged / Neoplasm Recurrence, Local / Neoplasm Staging / Netherlands / Pathology / Patients / Phenotype / Predictive Value of Tests / Risk factors / Surgery / Time Factors / Tissue Array Analysis / Treatment Outcome / Tumors