AB057. SOH23ABS_188. PDL-1 expression based on aetiology of mismatch repair deficiency—are there differences between molecularly lynch and sporadic colorectal cancer?

Background: Data regarding the response of Lynch syndrome (LS) colorectal cancer (CRC) to immune checkpoint inhibitors (ICIs) is scarce. Aim: to investigate differences in clinicopathological, local and systemic inflammation and programmed death-ligand 1 (PD-L1) expression as measured in tumour [Tumour Proportion Score (TPS)] and tumour plus immune cells [Combined Positive Score (CPS)] relative to all viable tumour cells.

Methods: Consecutive patients undergoing resection for CRC were identified from a prospectively maintained institutional database from January 2004 to December 2015 inclusive. Immunohistochemistry (IHC) was used to identify mismatch repair (MMR) status and PD-L1 expression. Molecular analysis for BRAFV600E mutation hotspot was performed selectively on MLH1-deficient tumours. Absence of MLH1, BRAF, MSH2, MSH6 or PMS2 were characterised as molecularly LS.

Results: A total of 238 mismatch repair deficient colorectal cancers (dMMR CRCs) were identified, with median follow up of 45 months (95% CI: 38.538, 51.462). Of these 91.5% (n=218) had tissue blocks adequate for PD-L1 IHC. In total 93 (39.1%) were characterised as LS and 145 (60.9%) were classified as sporadic. The mean age was 78.19 [standard deviation (SD) =30.826] and 64.26 (SD =14.756) respectively [mean difference (MD) 4.066; P<0.001]. Sporadic CRC were more commonly female (69.5%, P<0.001) and right-sided (90.3%, P<0.001). BRAF mutation was identified in 60.5% (n=144). There was no difference in KM scores (P=0.847) or modified Glasgow prognostic score (P=0.121). The 5-year overall survival rate was 79.1% and 76.5% (P=0.303), while 5-year disease-free survival was 75.4% and 67.4% (P=0.600) for sporadic CRC and LS tumours, respectively. There was a difference in mean TPS scores (P=0.003), but no difference in mean CPS scores (P=0.599).

Conclusions: There was no difference in markers of local or systemic immune response, and survival between groups. Although, there was a difference in TPS, there was no difference in CPS. These results suggest that there is unlikely to be a difference in ICI efficacy based on aetiology of dMMR in CRC.

Keywords: Immune checkpoint inhibitors (ICIs); colorectal cancer (CRC); programmed death-ligand 1 (PD-L1); mismatch repair deficiency; Combined Positive Score (CPS)