Strong Prognostic Value of Microsatellite Instability in Intestinal Type Non-cardia Gastric Cancer

Marrelli, Daniele; Połom, Karol; Pascale, Valeria; Vindigni, Carla; Piagnerelli, Riccardo; Franco, Lorenzo Giacinto De; Ferrara, Francesco; Roviello, Giandomenico; Garosi, Laurent; Petrioli, Roberto; Roviello, Franco

doi:10.1245/s10434-015-4931-3

Cited by 104 publications

(97 citation statements)

References 30 publications

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“…Microsatellite instability (MSI) has been reported, in several studies, as an important favourable prognostic factor for GC; we recently confirmed its prognostic value in a large series (9). Furthermore, in our experience we observed a different proportion of MSI cases in patients coming from high-risk or low-risk areas of Italy, being MSI more common in regions with higher GC incidence (manuscript to be submitted).…”

supporting

confidence: 72%

Ethnicity-related differences in tumor immunity: a new possible explanation for gastric cancer prognostic variability?

Marrelli

Połom

Roviello

2016

Transl. Gastroenterol. Hepatol.

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supporting

confidence: 72%

Ethnicity-related differences in tumor immunity: a new possible explanation for gastric cancer prognostic variability?

Marrelli

Połom

Roviello

2016

Transl. Gastroenterol. Hepatol.

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“…In multivariable analysis, a nonsignificant trend for better DFS and OS in MSI-high Asian GC patients was still evident following adjuvant chemo(radio)therapy treatment, even if the small number of patients with MSI-high status may have halted the formal achievement of a statistically significant result. Several retrospective studies shed light on the better prognosis of MSI-high GC patients following radical resection [2]. However, the clinical translation of MSI as a prognostic biomarker for GC patients has been hampered by the retrospective and heterogeneous nature of available series, the relatively low frequency of MSI-high status, and the potential detrimental effect of “over-treatments” with perioperative chemotherapy in MSI-high GC patients.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies showed that MSI-high GC patients show peculiar clinical and pathological features such as older age, female sex, low grade of differentiation and intestinal histotype, antral localization, and absence of nodal involvement [2]. Given the hypermutated status of MSI-high GC, a typical lymphocyte-rich histology is often observed [3].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Impact of Microsatellite Instability in Asian Gastric Cancer Patients Enrolled in the ARTIST Trial

Miceli

An²,

Bartolomeo

et al. 2019

Oncology

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Background: Caucasian patients with microsatellite instability (MSI)-high gastric cancer (GC) may have better prognosis but worse outcomes. Objective: Here we explored the prognostic role of MSI in Asian patients. Methods: This post hoc analysis comprehended radically resected GC patients randomized to XP (capecitabine/cisplatin) or XPRT. MSI status was assessed by combining immunohistochemistry with multiplex polymerase chain reaction. The MSI prognostic effect on disease-free survival (DFS) and overall survival (OS) was evaluated. Results: 393 tissue samples were analyzed and 35 (9%) were MSI-high. This subgroup was characterized by: older age, Borrmann classification 1–2, antral localization, T3–4 stage, and intestinal type. At univariable analysis, the microsatellite-stable subgroup showed a trend toward a worse prognosis as compared to the MSI-high group: 3-year DFS was 76.3 versus 85.4% (p = 0.122); 3-year OS was 81.7 versus 91.4% (p = 0.046). Multivariable analyses confirmed it in both DFS (hazard ratio, HR = 2.32 [95% CI 0.91, 5.88]; p = 0.077) and OS (HR = 3.17 [95% CI 0.97, 10.43]; p = 0.057). Conclusions: MSI-high status was associated with specific clinical-pathological features and a trend toward better outcomes of Asian GC patients.

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“…It is also illustrated that some genes acted differentially in diffuse GC and intestinal GC [7], [13], [14]; however, only a few prognostic biomarkers for specific subtype GC have been discovered. Several pilot studies showed transcriptome level difference between these two subtypes [7], [10], [15], [16], [17], yet large-scale, systematic, and comprehensive investigation of gene expression difference between diffuse GC and intestinal GC based on large populations is still needed to shed light on precious medication on different GC patients.…”

Section: Introductionmentioning

confidence: 99%

Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes

Min

Zhao

Zhu

et al. 2017

Translational Oncology

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BACKGROUND: Gastric cancer (GC) is the fifth leading cause of cancer-related deaths worldwide. As an effective and easily performed method, microscopy-based Lauren classification has been widely accepted by gastrointestinal surgeons and pathologists for GC subtyping, but molecular characteristics of different Lauren subtypes were poorly revealed. METHODS: GSE62254 was used as a derivation cohort, and GSE15459 was used as a validation cohort. The difference between diffuse and intestinal GC on the gene expression level was measured. Gene ontology (GO) enrichment analysis was performed for both subgroups. Hierarchical clustering and heatmap exhibition were also performed. Kaplan-Meier plot and Cox proportional hazards model were used to evaluate survival grouped by the given genes or hierarchical clusters. RESULTS: A total of 4598 genes were found differentially expressed between diffuse and intestinal GC. Immunity- and cell adhesion–related GOs were enriched for diffuse GC, whereas DNA repair– and cell cycle–related GOs were enriched for intestinal GC. We proposed a 40-gene signature (χ2 = 30.71, P < .001) that exhibits better discrimination for prognosis than Lauren classification (χ2 = 12.11, P = .002). FRZB [RR (95% CI) = 1.824 (1.115-2.986), P = .017] and EFEMP1 [RR (95% CI) = 1.537 (0.969-2.437), P = .067] were identified as independent prognostic factors only in diffuse GC but not in intestinal GC patients. KRT23 [RR (95% CI) = 1.616 (0.938-2.785), P = .083] was identified as an independent prognostic factor only in intestinal GC patients but not in diffuse GC patients. Similar results were achieved in the validation cohort. CONCLUSION: We found that GCs with different Lauren classifications had different molecular characteristics and identified FRZB, EFEMP1, and KRT23 as subtype-specific prognostic factors for GC patients.

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Strong Prognostic Value of Microsatellite Instability in Intestinal Type Non-cardia Gastric Cancer

Abstract: MSI was confirmed as a significant predictor of long term outcome in a large series of GC with a long follow-up time, but the prognostic value is limited to selected histotypes of non-cardia tumors.

Cited by 104 publications

References 30 publications

Ethnicity-related differences in tumor immunity: a new possible explanation for gastric cancer prognostic variability?

Ethnicity-related differences in tumor immunity: a new possible explanation for gastric cancer prognostic variability?

Prognostic Impact of Microsatellite Instability in Asian Gastric Cancer Patients Enrolled in the ARTIST Trial

Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes

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