Assessing molecular subtypes of gastric cancer: microsatellite unstable and Epstein-Barr virus subtypes. Methods for detection and clinical and pathological implications

Abstract

BackgroundThe molecular classification of gastric cancer recognises two subtypes prone to immune checkpoint blockade: the microsatellite unstable and the Epstein-Barr virus (EBV)-related tumours. We aim to assess the concordance between immunohistochemistry and PCR for microsatellite status evaluation, and explore the value of microsatellite instability (MSI) and EBV as predictive survival factors.Material and methodsWe collected 246 consecutively diagnosed gastric cancer cases in all stages and evaluated the microsatellite status using immunohistochemistry for mismatched repair (MMR) proteins and PCR. EBV expression was studied through in situ hybridisation.ResultsForty-five (18%) cases presented MSI and 13 (6%) were positive for EBV. MSI was associated with female sex, older age, distal location and distal non-diffuse type of the modified Lauren classification. EBV expression was most frequent in proximal location and proximal non-diffuse type. The sensitivity, specificity, positive predictive value and negative predictive value of immunohistochemistry for the microsatellite study were 91%, 98%, 91% and 98%, respectively. In the multivariate analysis, MSI was an independent predictor of favourable tumour-specific survival (TSS) in stages I–III (MSI: HR: 0.37, 95% CI 0.12 to 0.95, p=0.04).ConclusionsThe MSI status and the EBV expression should be incorporated in routine pathological report for two reasons. First, MSI defines a different pathological entity with a better outcome. Second, MSI and EBV may be useful biomarkers to identify patients who will respond to immune checkpoint blockade inhibitors. For this purpose, immunohistochemical study for MMR proteins and in situ hybridisation study for EBV evaluation are feasible and cost-effective methods.

Molecular Classification of Gastric Cancer among Alaska Native People

“…The incidence of MMR deficiency among AN patients is 10%, similar to Asians [57], and lower than the 22% that has been observed in Western populations, 22% [13,58,59]. A positive association was observed between MMR deficiency and patients who are female, over the age of 50, have an SNV mutation, and cancer in the distal stomach, consistent with the studies analyzing MMR deficiency with clinicopathological factors [60,61]. We, however, did not observe a correlation with subtype, which has been observed in some studies [57,62], but not others [58,59].…”

Clinical characteristics and prognostic significance of TCGA and ACRG classification in gastric cancer among the Chinese population

“…In the present study, the MSI type accounted for ~21.5% of all GC cases, was diagnosed at relatively older ages and was more common in females. Previous studies have shown that the majority of patients with MSI type exhibited intestinal-type GC predominantly located in the distal stomach; the majority of these patients were female and displayed an association with age (5,13,14). In the present study, sequencing revealed that the mutation rate of ARID1A and CDH1 were 21.5 and 3.1%, respectively.…”

Clinicopathological Significance of EBV-Infected Gastric Carcinomas: A Meta-Analysis

“…In the present study, the estimated EBV positive rate was 11.3%. EBV positive rates ranged from 1.2% to 89.2% in the individual eligible studies [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , …”