Microsatellite instability and PDL1 expression in small bowel adenocarcinoma - potential for immune checkpoint inhibitor therapies

Date

09 Oct 2016

Session

Poster display

Presenters

Muhammad Alvi

Citation

Annals of Oncology (2016) 27 (6): 359-378. 10.1093/annonc/mdw378

Authors

M.A. Alvi1, S. McQuaid1, R. Wilson2, M. Salto-Tellez1

Author affiliations

  • 1 Centre For Cancer Research And Cell Biology, Queen's University Belfast, BT9 7AE - Belfast/GB
  • 2 Centre For Cancer Research And Cell Biology, Belfast City Hospital Northern Ireland Cancer Centre, School of Medicine, Dentistry & Biomedical Science, BT9 7AE - Belfast/GB
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Background

Small bowel adenocarcinoma (SBA) is a rare disease but incidence rates are on the rise. Management of SBA is challenging as there is a dearth of known molecular markers and the role and type of adjuvant chemotherapy is also not well defined. Expression of PDL1 in microsatellite instable (MSI) colorectal cancer makes an attractive target for immune checkpoint inhibitor therapies. In this study we have tested this hypothesis in SBA.

Methods

Using a retrospective 28 patient matched normal-tumour cohort we investigated MSI using a PCR assay looking at five mononucleotide repeat markers (BAT-25, BAT-26, NR-21, NR-24 and MONO-27). MSI was called where three or more markers were affected. PDL1 immunohistochemistry was carried out on a Ventana Benchmark XT platform using PD-L1/CD274 (SP142) antibody at 1:40 dilution. Scoring was done separately for epithelial tumour cells along the invasive front, peritumoural lymphoid follicles and intra-tumoural lymphoid cells using four grades: negative (for no staining), low, moderate and high.

Results

Six cases were identified to be MSI. As shown in Table 1 out of these we observed five to have a high PDL1 expression in both peritumoural lymphoid follicles and epithelial tumour cells along the invasive front. We observed low PDL1 expression in intra-tumoural lymphoid cells in all samples.

Case PDL1 expression in MSI small bowel adenocarcinoma cases
Epithelial tumour cells along the invasive front Peritumoural lymphoid follicles Intra-tumoural lymphoid cells
1 high high low
2 high high low
3 high high low
4 high high low
5 high high low
6 negative moderate low

Conclusions

Our study shows that 20% of SBAs are MSI and 80% of these have a high expression of PDL1. This makes these cases an ideal candidate for immune checkpoint inhibitor therapies targeting PDL1.

Clinical trial identification

Legal entity responsible for the study

Queen's Univeristy Belfast

Funding

Cancer Research UK, Experimental Cancer Medicine Centre Network, Sean Crummey Memorial Fund, Tom Simms Memorial Fund, Friends of the Cancer Centre and HSC Public Health Agency

Disclosure

All authors have declared no conflicts of interest.

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