High microsatellite instability (MSI-H) is associated with distinct clinical and molecular characteristics and an improved survival in early Colon cancer (CC); real world data from the AIO molecular registry Colopredict Plus

Abstract

Colorectal cancer is one of the leading malignancies and still accounts for almost 25 000 deaths in Germany each year. Although there is accumulating data on the molecular basis, treatment and clinical outcome of patients within clinical trials evidence from the real-world setting is mostly lacking. We started the molecular registry trial Colopredict Plus in 2013 to collect clinical and molecular data from a real-world cohort of patients with early colon cancer stage II and III in 70 German colon cancer centers focusing on the prognostic impact of high microsatellite instability. In this interim report, we characterize a clinical cohort of 2615 patients, of whom 1787 tissue probes were analyzed. Microsatellite status was assessed using immunhistochemistry and fragment length analysis, with a concordance of 91.4 %. These established histopathological methods are sensitive and cost-effective. The median age was 72 years, significantly higher compared to clinical trial populations, with a median Charlson Comorbidity Index of 3. The stage-dependent incidence of microsatellite instability was 23.7 % and was associated with female gender, BRAF-mutation, UICC stage II and localization in the right colon. Survival calculated in disease free, relapse free and overall survival significantly differed between MSI-H and MSS, in favor of MSI-H patients. Multivariate age-adjusted analyses of relapse-free survival, disease-free survival, and overall survival highlighted microsatellite instability as a robust and positive prognostic marker for early colon cancer independent of age.

Causes of mortality in elderly UICC stage III colon cancer (CC) patients––Tumor‐related death and competing risks from the German AIO colorectal study group Colopredict Plus (CPP) registry

“…20 , 21 Among the elderly, BRAF‐mutated MSI‐H tumors were more frequent. 21 , 22 , 23 As anticipated, co‐morbidities calculated with the Charlson comorbidity score were significantly higher in elderly than in younger pts. Mean Charlson comorbidity score of pts.…”

“…Our cohort contained slightly more men than women (52% vs. 48%) and right‐sided CCs 20,21 . Among the elderly, BRAF‐mutated MSI‐H tumors were more frequent 21–23 . As anticipated, co‐morbidities calculated with the Charlson comorbidity score were significantly higher in elderly than in younger pts.…”

Relationship of HER2 Alteration and Microsatellite Instability Status in Colorectal Adenocarcinoma

“…Microsatellite instability‐high (MSI‐H) occurred for less than 5% in patients with metastatic CRC and it is found to be more common in patients with BRAF V600E mutation [ 19 ]. A previous study showed that MSI and PIK3CA mutations were associated with ERBB2/ERBB3 mutations [ 12 ].…”

Microsatellite instability (MSI-H) is associated with a high immunoscore but not with PD-L1 expression or increased survival in patients (pts.) with metastatic colorectal cancer (mCRC) treated with oxaliplatin (ox) and fluoropyrimidine (FP) with and without bevacizumab (bev): a pooled analysis of the AIO KRK 0207 and RO91 trials

“…which may offer individualized therapy strategies. Well-known positive prognostic factor for CRC is MSI-H especially in early stages (Noepel-Duennebacke et al 2020 ). MSI-H patients (pts.)…”