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International Journal of Clinical Oncology

, Volume 23, Issue 3, pp 504–513 | Cite as

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

  • Rin Yamada
  • Tatsuro Yamaguchi
  • Takeru Iijima
  • Rika Wakaume
  • Misato Takao
  • Koichi Koizumi
  • Tsunekazu Hishima
  • Shin-ichiro Horiguchi
Original Article
  • 338 Downloads

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 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.

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 BRAF V600E mutation analysis and MLH1 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%, 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).

Conclusions

Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.

Keywords

Microsatellite instability Colorectal cancer Lynch syndrome PD-L1 

Notes

Acknowledgements

The authors would like to acknowledge all the patients and their families.

Funding

The present study was supported in part by the Office of Metropolitan Hospital Management, Tokyo Metropolitan Government.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

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Copyright information

© Japan Society of Clinical Oncology 2018

Authors and Affiliations

  1. 1.Department of PathologyTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
  2. 2.Department of Clinical GeneticsTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
  3. 3.Hereditary Tumor Research ProjectTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
  4. 4.Department of SurgeryTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
  5. 5.Department of GastroenterologyTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan

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