MSI as a predictive factor for treatment outcome of gastroesophageal adenocarcinoma

Abstract

Gastroesophageal cancers are a major cause of death worldwide and treatment outcomes remain poor. Adequate predictive biomarkers have not been identified. Microsatellite instability (MSI) as a result of mismatch repair deficiency is present in four to twenty percent of gastroesophageal cancers and has been associated with favorable survival outcomes compared to microsatellite stable tumors. This prognostic advantage may be related to immunosurveillance, which may also explain the favorable response to immune checkpoint inhibition observed in MSI high (MSI-H) tumors. The value of conventional cytotoxic treatment in MSI-H tumors is unclear and results on its efficacy range from detrimental to beneficial effects. Here the recent data on MSI as a predictive factor for outcome of gastroesophageal cancer treatment is reviewed.

Genomic analysis of response to neoadjuvant chemotherapy in esophageal adenocarcinoma

“…We performed assessment of somatic copy number variations (CNVs), small insertions/deletions (indels) and variant calling of somatic single nucleotide variants (SNVs) as previously described (Frankell et al 2019; Li et al 2018; Noorani et al 2017; Secrier et al 2016). Two non-responders were found to have microsatellite instability (MSI) (Patient 27, score= 5.63 and Patient 29, score= 3.44) and these were excluded because MSI-High tumors are known to respond to immune checkpoint blockade, providing a potential treatment pathway for these patients (van Velzen et al 2020).…”

Microsatellite instability in Gastric Cancer: Between lights and shadows

“…The good prognostic impact of MSI-high status following radical surgery has been shown also by several post-hoc analyses of RCTs [6,8,63]. On the other hand, since adjuvant and perioperative chemotherapy are guideline-endorsed treatment for GC, many research groups have investigated the predictive role of MSI status in chemotherapy response [64,65] (Table 1). For example, a large-scale study, involving 1,990 GC patients assessed whether MSI status was helpful in predicting patients which would benefit from 5-fluorouracilbased adjuvant chemotherapy after R0 resection [66].…”

The evolving landscape of predictive biomarkers in immuno‐oncology with a focus on spatial technologies

“…There are currently two approaches to detecting MSI-high and MMRdeficient tumors in clinics, polymerase chain reaction (PCR) and IHC. 47 Although MSI-high has been reported in multiple solid tumors, it varies across different types of tumors. 48 CRC, endometrial and gastric cancers have the highest frequencies (> 10%), while glioblastomas, oesophageal cancer, breast cancer and non-smallcell lung cancer (NSCLC) have the lowest frequencies (< 2%).…”

“…Pembrolizumab has been approved by the FDA for the treatment of MSI‐high/MMR‐deficient tumors. There are currently two approaches to detecting MSI‐high and MMR‐deficient tumors in clinics, polymerase chain reaction (PCR) and IHC 47 . Although MSI‐high has been reported in multiple solid tumors, it varies across different types of tumors 48 .…”