Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-01-11

AUTHORS

Rin Yamada, Tatsuro Yamaguchi, Takeru Iijima, Rika Wakaume, Misato Takao, Koichi Koizumi, Tsunekazu Hishima, Shin-ichiro Horiguchi

ABSTRACT

BackgroundThe field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients.MethodsAmong 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations.ResultsThe following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55–37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50–45.0, P = 0.176).ConclusionsTherefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1. More... »

PAGES

504-513

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10147-018-1238-y

DOI

http://dx.doi.org/10.1007/s10147-018-1238-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1100317767

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29327160


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81 methylation
82 methylation analysis
83 microsatellite instability
84 mismatch repair germline mutations
85 morphology
86 mutation analysis
87 mutations
88 patients
89 poor differentiation
90 present study
91 profile
92 promoter methylation
93 reaction
94 regression analysis
95 repair (MMR) germline mutations
96 resection
97 solid type
98 sporadic MSI cancers
99 sporadic MSI tumors
100 sporadic microsatellite instability
101 study
102 subgroups
103 surgical resection
104 syndrome
105 terms
106 tumors
107 types
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