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- Title
Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer.
- Authors
Yamada, Rin; Yamaguchi, Tatsuro; Iijima, Takeru; Wakaume, Rika; Takao, Misato; Koizumi, Koichi; Hishima, Tsunekazu; Horiguchi, Shin-ichiro
- Abstract
Background: The 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 <italic>MLH1</italic> 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.Methods: Among 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 <italic>BRAF</italic> V600E mutation analysis and <italic>MLH1</italic> methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations.Results: The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, <italic>P</italic> = 0.0002), especially solid type (30.6 vs. 3.6%, <italic>P</italic> = 0.0061); medullary morphology (19.4 and 0%, <italic>P</italic> = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, <italic>P</italic> = 0.042), and PD-L1 expression (25.0 vs. 3.6%, <italic>P</italic> = 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, <italic>P</italic> = 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, <italic>P</italic> = 0.176).Conclusions: Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.
- Subjects
HEREDITARY nonpolyposis colorectal cancer; APOPTOSIS; MICROSATELLITE repeats; JAPANESE people; CANCER histopathology; DNA repair; GENE expression; DISEASES
- Publication
International Journal of Clinical Oncology, 2018, Vol 23, Issue 3, p504
- ISSN
1341-9625
- Publication type
Article
- DOI
10.1007/s10147-018-1238-y