Synchronous metastatic gastric cancer-molecular background and clinical implications with special attention to mismatch repair deficiency

Połom, Karol; Böger, Christine; Smyth, Elizabeth; Marrelli, Daniele; Behrens, Hans‐Michael; Marano, Luigi; Becker, Thomas; Lordick, Florian; Röcken, Christoph; Roviello, Franco

doi:10.1016/j.ejso.2018.02.208

Cited by 16 publications

(11 citation statements)

References 30 publications

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“…A subgroup analysis in the same cohort showed that the prognostic advantage of MSI-H is present within the same disease stage in resectable gastric cancer and even holds up for stage IV disease [41]. However, this prognostic value of MSI in stage IV gastric cancer was not seen in a different series of 510 stage I-IV gastric cancer patients that underwent gastrectomy including 83 MSI-H tumors [47].…”

Section: Prevalence Of Msi In Gastroesophageal Adenocarcinomamentioning

confidence: 96%

“…Between 6 and 24% of resected gastroesophageal adenocarcinomas are reported to be MSI-H [20,[34][35][36][37][38][39], and this may even mount up to 48% in patients of 85 years and older [40]. However, the percentage sharply drops to less than 10% in patients with synchronous metastatic disease [41], and less than 5% in a beyond-second line treatment setting [19]. MSI is only rarely observed in non-junctional esophageal cancers [42][43][44].…”

Section: Prevalence Of Msi In Gastroesophageal Adenocarcinomamentioning

confidence: 99%

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MSI as a predictive factor for treatment outcome of gastroesophageal adenocarcinoma

Velzen

Derks

Grieken

et al. 2020

Cancer Treatment Reviews

100

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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.

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Section: Prevalence Of Msi In Gastroesophageal Adenocarcinomamentioning

confidence: 96%

Section: Prevalence Of Msi In Gastroesophageal Adenocarcinomamentioning

confidence: 99%

MSI as a predictive factor for treatment outcome of gastroesophageal adenocarcinoma

Velzen

Derks

Grieken

et al. 2020

Cancer Treatment Reviews

100

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“…According to TCGA, the MSI subgroup is linked with hypermutation, gastric CpG island methylator phenotype, MLH1 silencing, and mitotic pathways [ 1 ]. In the last few years, many publications described MSI from a clinical point of view, being found in 5.6% to 33.3% of all gastric cancers and strongly associated with female sex, older age, intestinal histotype, middle/lower gastric position, N0 status, and TNM stage I/II with favorable overall survival [ 1 , 2 , 3 , 4 , 5 ]. It is important to underline that MSI is not a homogenous group and it has been shown that MSI is a prognostic factor because of the association with tumor localization and Lauren classification [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…The molecular diagnosis of MSI gastric cancer is of highest importance, especially before multidisciplinary treatment. It presents different responses to neoadjuvant chemotherapy and requires specific surgical treatment in synchronous metastases, includes the possibility of tailored lymphadenectomy, and stratifies for the application of targeted therapies [ 3 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

The Thomsen-Friedenreich Antigen: A Highly Sensitive and Specific Predictor of Microsatellite Instability in Gastric Cancer

Mereiter

Połom

Williams³

et al. 2018

JCM

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Microsatellite instability (MSI) is a distinct molecular subtype of gastric cancer. In recent years, the clinical consequences of MSI and the therapeutic opportunities to target this peculiar cancer subtype became evident. However, despite the importance of MSI for the stratification of patients, the time and resources required for diagnosis still present an obstacle. In an attempt to identify a new marker for MSI in gastric cancer, we evaluated the expression of five cancer-associated glycan epitopes in a cohort of 13 MSI and 17 microsatellite stable (MSS) cases. Our analysis revealed a highly significant (p < 0.001) association between the expression of the Thomsen-Friedenreich (TF) antigen and MSI status. Hence, we present here the identification of the first single marker for MSI in gastric cancer, excelling with a specificity of 94% (16/17), sensitivity of 69.2% (9/13), negative predictive value of 80% (16/20), and positive predictive value of 90% (9/10). The TF antigen, detected by simple antibody-based assays, is highly specific for carcinoma being undetectable in gastric healthy and premalignant epithelia. This finding lays the basis for new studies and holds promise in improving the rapid identification of MSI in the clinical setting.

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“…Accordingly, recent evidence points to a positive prognostic role for MSI-H status in surgically treated stage IV AGC 18 , though no data are available on the role of MSI status neither in 6 patients undergoing metastasectomy nor preoperative chemotherapy followed by metastasectomy. In the advance-disease setting, the potential predictive role of MSI status warrants further investigation particularly in light of the suggested benefit of oligometastatic GC from multimodality approach.…”

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confidence: 99%

Oligometastatic gastric cancer: An emerging clinical entity with distinct therapeutic implications

Salati

Valeri

Spallanzani

et al. 2019

European Journal of Surgical Oncology

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Gastric cancer (GC) remains responsible for a high burden worldwide being the third leading cause of cancer-related mortality. Most of patients present at an advanced stage at diagnosis and are thus candidate to standard chemotherapy resulting in median survival of less than 1 year. Oligometastatic gastric cancer is an increasingly recognized clinical entity characterized by limited metastatic spread that has been showing to benefit from aggressive multimodality strategies encompassing chemotherapy and surgery. The ongoing RENAISSANCE/AIO-FLOT5 (NCT02578368) phase III trial is aimed at evaluating if neoadjuvant chemotherapy followed by surgical resection of the primary tumour and metastases (if suitable) could become the new standard of care for oligometastatic GC. In the meantime, in addition to currently available clinical parameters, the emerging predictive/prognostic role of biomarkers such mismatch repair deficiency/microsatellite instability high status needs to be specifically addressed also in this subgroup of GC to assist in patient selection.

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Synchronous metastatic gastric cancer-molecular background and clinical implications with special attention to mismatch repair deficiency

Cited by 16 publications

References 30 publications

MSI as a predictive factor for treatment outcome of gastroesophageal adenocarcinoma

MSI as a predictive factor for treatment outcome of gastroesophageal adenocarcinoma

The Thomsen-Friedenreich Antigen: A Highly Sensitive and Specific Predictor of Microsatellite Instability in Gastric Cancer

Oligometastatic gastric cancer: An emerging clinical entity with distinct therapeutic implications

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