Predictive model for high‐frequency microsatellite instability in colorectal cancer patients over 50 years of age

Abstract

Microsatellite instability (MSI) is an important biomarker for screening for Lynch syndrome, and also of response to immune checkpoint inhibitors. The aim of this study is to create a predictive model to determine which elderly patients with colorectal cancer (CRC) should undergo MSI and/or immunohistochemistry testing on the basis of clinicopathological data. We analyzed a test cohort of CRC patients aged ≥50 years (n = 2219) by multivariate logistic regression analyses to identify predictors of high‐frequency MSI (MSI‐H). The created prediction model was validated in an external cohort (n = 992). The frequency of MSI‐H was 5.5% among CRC patients aged ≥ 50 years. The following five predictors of MSI‐H were identified in the test cohort: female (1 point), mucinous component (2 points), tumor size ≥ 60 mm (2 points), location in proximal colon (3 points), and BRAF mutation (6 points). The area under curve (AUC) in the receiver‐operating characteristic (ROC) analysis of this prediction model was 0.832 (95% confidence interval: 0.790–0.874). The sensitivity and specificity were 74.4% and 77.7%, respectively, for a cut‐off score of 4 points. The receiver‐operating characteristic curve of the validation cohort also showed an AUC of 0.856 (95% CI: 0.806–0.905). This prediction model is useful to select elderly CRC patients who should undergo MSI testing, and who may benefit from treatment with 5‐FU‐based adjuvant chemotherapy and cancer immunotherapy.

Immunohistochemical Expression of MMR Proteins with Clinicopathological Correlation in Colorectal Cancer in Egypt

“…MSS is the case when no markers are unstable. We follow Fujiyoshi et al, 2017 study definition of MSI that was approved for Bethesda [2], [22]. In Fujiyoshi et al, 2017 study, they include MSI-L as MSS.…”

“…Colorectal cancer (CRC) is the most commonly observed cancer worldwide [1]. It is one of the most common cause of cancer-related death worldwide [2]. Cancer colon, as any cancer is caused by environmental and genetic factors [3].…”

Multicenter Phase I/II Trial of Napabucasin and Pembrolizumab in Patients with Metastatic Colorectal Cancer (EPOC1503/SCOOP Trial)

“…Immune checkpoint inhibitors targeting the programmed cell death-ligand 1 (PD-L1) and programmed cell death-1 (PD-1) pathway have shown durable responses in patients with microsatellite instability high (MSI-H) metastatic colorectal cancer (mCRC), a population that constitutes 3-5% of patients with mCRC. [1][2][3] In contrast, anti-PD-1/PD-L1 antibodies have little clinical benefit in patients with microsatellite-stable (MSS) mCRC. 1,4,5 Although most patients with MSS mCRC do not have T-cell infiltration and are considered the so-called "cold tumors", 6 the mechanism underlying immune resistance in such tumors remains poorly understood.…”

Development and validation of MMR prediction model based on simplified clinicopathological features and serum tumour markers

“…Previous studies have demonstrated that MMR status of CRC is significantly correlated with their clinicopathological features [ 17 , 18 ] and serum tumour biomarkers (STMs) [ 19 , 20 ]. Though several prediction models based on pathological features have been developed, the complex pathological characteristics included in previous models required detailed pathological diagnosis [ [21] , [22] , [23] ], which not only caused a huge burden on the pathologists, but also lacked of instructive value for clinicians. STMs are both important prognostic factors and the indicators of therapeutic effect and recurrence in patients with CRC [ 19 , 24 ], whereas their predictive value for MMR status has not been assessed in previous studies.…”