Microsatellite Instable Colorectal Adenocarcinoma Diagnostics: The Advent of Liquid Biopsy Approaches

Abstract

The introduction of immunotherapy has revolutionized the oncological targeted therapy paradigm. Microsatellite instability (MSI) identifies a subgroup of colorectal cancers (CRCs) which respond to treatment with immune checkpoint inhibitors. Tissue biopsy is currently the gold standard for the assessment of MSI/Mismatch Repair deficiency (MMRd) by means immunohistochemistry or molecular assays. However, the application of liquid biopsy in the clinic may help to overcome several limitations of tissue analysis and may provide great benefit to the diagnostic scenario and therapeutic decision-making process. In the context of MSI/MMRd CRC, the use of liquid biopsy may allow to establish MSI/MMR status if tissue sampling cannot be performed or in case of discordant tissue biopsies. Liquid biopsy may also become a powerful tool to monitor treatment response and the onset resistance to immunotherapy over time and to stratify of MSI/MMRd patients according to their risk of relapse and metastases. The aim of this review is to summarize the main technical aspects and clinical applications, the benefits, and limitations of the use of liquid biopsy in MSI/MMRd colorectal cancer patients.

Signet ring-cell colorectal adenocarcinoma: review and clinical case

“…Ряд исследований продемонстрировало более высокую долю фенотипа (20-48%) микросателлитной нестабильности (MSI-H) при SRCC по сравнению с AC [16]. Также стоит отметить особый эпигенотип CIMP, который обычно имеет MSI-H, т. к. происходит метилирование белков системы репарации ДНК (MLH1, PMS2, MSH2, MSH6) [17]…”

“…В другом случае выпадения ядерной экспрессии MLH1, связанной с более частой в SRCC, по сравнению с AC, мутацией гена BRAF [16,30], возможно проведение теста с антителом против BRAF V600E (самая частая вариация данной мутации) для дифференцировки диагноза. При этом указанные патологии могут привести к возникновению микросателлитной нестабильности (MSI) [31], которая также ассоциирована с фено типом избыточного метилирования CpG-остров ков (CIMP) [32,33].…”

The ideal reporting of RAS testing in colorectal adenocarcinoma: a pathologists’ perspective

“…High-sensitive microfluidic platforms and automated RT-PCR systems demonstrated technical feasibility to accurately detect MSI status on diagnostic specimens. Several NGS assays are currently in use to provide comprehensive data regarding hot spot mutations and MSI status combining ultra-sensitive systems with an optimized bioinformatic algorithm aimed to promote a single-step multi-testing analysis system for the clinical management of CRC patients 68 , 69 .…”

FGFR2 testing in cholangiocarcinoma: translating molecular studies into clinical practice

“…Liquid biopsy is emerging as a promising minimally invasive tool for biomarker testing in solid tumors. Liquid biopsy approaches may overcome challenges associated with molecular profiling of tissue samples, including insufficient tumor cellularity, molecular intratumor heterogeneity and the impossibility to perform serial biopsy sampling to monitor the onset of resistance to targeted therapy 84 . However, the low fraction of ctDNA retrieved from blood samples may challenge the sensitivity of liquid biopsy-based assays for solid tumors, including CCA.…”