Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer

Choi, Yoon Young; Kim, Hyunki; Shin, Su‐Jin; Kim, Ha Yan; Lee, Jinae; Yang, Han Kwang; Kim, Woo Ho; Kim, Young Woo; Kook, Myeong Cherl; Park, Young Kyu; Kim, Hyung‐Ho; Lee, Hye Seung; Lee, Kyung Hee; Gu, Mi Jin; Choi, Seung Ho; Hong, Soon Won; Kim, Jong Won; Hyung, Woo Jin; Noh, Sung Hoon; Cheong, Jae‐Ho

doi:10.1097/sla.0000000000002803

Cited by 221 publications

(217 citation statements)

References 46 publications

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“…An important result observed in the present study was the absence of benefit from POP/AD treatment to MSI subgroup defined by IHC, similar to the findings previously described in phase III trials . Furthermore, we found a higher proportion of MSI compared with MAGIC and CLASSIC trials (17.4% vs 8.2% and 6.8% respectively), in addition to 10% EBV positive tumors.…”

Section: Discussionsupporting

confidence: 91%

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Gastric cancer molecular classification and adjuvant therapy: Is there a different benefit according to the subtype?

Ramos

Pereira

Amorim

et al. 2019

Journal of Surgical Oncology

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Background Gastric cancer (GC) has been defined in distinct molecular subtypes with different therapeutic implications. However, its clinical significance and prognosis regarding standard chemotherapy (CMT) remains unclear. This study aimed to analyze the impact of perioperative or adjuvant treatment among subtypes of GC. Methods We retrospectively evaluated all stage II/III patients with GC who underwent a curative gastrectomy. Based on immunohistochemistry and in situ hybridization techniques, GC was classified into five subtypes: Epstein‐Barr virus (EBV) positive, microsatellite instability (MSI), e‐cadherin aberrant, p53‐aberrant, and p53‐normal. Results Among the 178 CG included, 111 patients received CMT and 67 were treated with surgery alone. Survival analysis showed that p53‐aberrant GC treated with CMT had better disease‐free survival (DFS) compared with surgery alone (P = .001).There was no significant difference in DFS between patients who received CMT and those with surgery alone for EBV, MSI, E‐cadherin, and p53‐normal GC. An improvement in overall survival was observed only for E‐cadherin (P = .001) and p53‐aberrant (P < .001) patients who received CMT. Conclusions CMT showed different impact on the survival of CG according to the molecular subtype. No survival benefit was observed for EBV and MSI groups who received CMT. GC with p53‐aberrant had a significant benefit in survival with standard therapy.

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Section: Discussionsupporting

confidence: 91%

“…In MAGIC and CLASSIC trials MSI GC had a better prognosis irrespective of treatment received, and it is postulated that the production of new immunogenic epitopes due to the defective repair system activates peritumoral lymphocyte infiltration and systemic T cell activation, which could be downregulated by cytotoxic chemotherapy …”

Section: Discussionmentioning

confidence: 99%

Gastric cancer molecular classification and adjuvant therapy: Is there a different benefit according to the subtype?

Ramos

Pereira

Amorim

et al. 2019

Journal of Surgical Oncology

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“…MSI status was not a clear predictive biomarker of the effect of adding radiotherapy to adjuvant chemotherapy. Noteworthy, based on the CLASSIC study results [13] and the well-known greater benefit from chemotherapy in Asian GC patients, adjuvant chemotherapy may not be detrimental, but neither beneficial, in MSI-high Asian GC patients, and the same is true for adjuvant radiation treatment based on the present study results. Future prospective trials should investigate the omission of chemotherapy in patients with a lower clinico-pathological risk and MSI-high GC.…”

Section: Discussionsupporting

confidence: 63%

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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“…Regarding adjuvant treatment, Choi reported in a secondary analysis of the CLASSIC trial (comparing surgery and adjuvant chemotherapy with surgery alone) a better relapse‐free survival of MSI‐H cancer patients after surgery alone in comparison to non‐MSI‐H cancer patients. No benefit of adjuvant chemotherapy was observed among the MSI‐H cancer patients . In a big retrospective cohort study including 1,276 patients, Kim et al showed that patients with stage II/III MSI‐H tumors had no benefit of adjuvant chemotherapy; in addition, even a detrimental effect of adjuvant chemotherapy was observed in subgroups with stage III disease, undifferentiated histology and diffuse type tumors …”

Section: Discussionmentioning

confidence: 99%

“…In gastric cancer the prognostic implications are less clear. A better outcome for patients with MSI‐H tumors than with MSS tumors has been reported in a recent meta‐analysis by Polom and colleagues, whereas the benefit of perioperative or adjuvant chemotherapy seems to be unclear according to exploratory analyses of recent phase III trials …”

Section: Introductionmentioning

confidence: 95%

Prognostic significance of microsatellite‐instability in gastric and gastroesophageal junction cancer patients undergoing neoadjuvant chemotherapy

Haag

Czink

Ahadova

et al. 2019

Intl Journal of Cancer

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Perioperative systemic treatment is standard of care for Caucasian patients with locally advanced, resectable gastric adenocarcinoma. The prognostic relevance of the microsatellite instability (MSI) status in patients undergoing neoadjuvant chemotherapy followed by resection is unclear. We analyzed the association of the MSI status with histological regression and clinical outcome in patients undergoing neoadjuvant systemic treatment. Tumor tissue from patients undergoing neoadjuvant chemotherapy followed by resection for gastric or gastroesophageal‐junction adenocarcinoma was analyzed for MSI status using a mononucleotide marker panel encompassing the markers BAT25, BAT26, and CAT25. Histological regression, relapse‐free survival and overall survival were calculated and correlated with MSI status. We identified the MSI‐H phenotype in 9 (8.9%) out of 101 analyzed tumors. Though a poor histological response was observed in eight out of nine MSI‐H patients, overall survival was significantly better for patients with MSI‐H compared to MSS tumors (median overall survival not reached vs. 38.6 months, log‐rank test p = 0.014). Among MSI‐H patients, an unexpected long‐term survival after relapse was observed. Our data indicate that the MSI‐H phenotype is a favorable prognostic marker in gastric cancer patients undergoing neoadjuvant treatment. The benefit of perioperative cytotoxic treatment in patients with MSI‐H gastric cancer, however, remains questionable. Future trials should stratify patients according to their MSI status, and novel treatment modalities focusing on MSI‐H tumors should be considered.

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Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer

Abstract: MSI status and PD-L1 expression are clinically actionable biomarkers for stratifying patients and predicting benefit from adjuvant chemotherapy after D2 gastrectomy for stage II/III gastric cancer.

Cited by 221 publications

References 46 publications

Gastric cancer molecular classification and adjuvant therapy: Is there a different benefit according to the subtype?

Gastric cancer molecular classification and adjuvant therapy: Is there a different benefit according to the subtype?

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

Prognostic significance of microsatellite‐instability in gastric and gastroesophageal junction cancer patients undergoing neoadjuvant chemotherapy

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