Impact of MET variants on PD-L1 expression in pleomorphic lung carcinoma

Abstract

5Department of Histopathology, Imperial College London -Hammersmith Hospital, London, UK Background: Pleomorphic Lung Carcinoma (PC) is a rare subtype of NSCLCs poorly responsive to systemic therapy. It is a heterogenous tumour with both epithelial and sarcomatoid components. MET variants are targetable aberrations and have recently been reported to be more frequent in PCs. The relationship between MET and PD-L1 expression is not well understood. We determined PD-L1 expression in PCs and its relationship with MET variants. Methods: 80 cases of pleomorphic carcinoma were identified from the biobank and diagnostic archives of Royal Brompton Hospital and Imperial College Healthcare NHS trust. DNA was isolated for determination of a. MET copy number by digital droplet PCR (ddPCR) and b. Genomic MET aberrations by NGS. IHC of PD-L1 (28-8) with% positive cells were scored by two pathologists independently and>49% tumour staining was defined as high. Results: 78 cases were evaluated for PD-L1 status with a median score of 44%. 23/63 (36%) cases had MET CN of>2.2. METex14 splice variants were identified in 5/73 (7.2%) cases. 2/73 (2.7%) cases had deleterious MET mutations. By MET CN status: low/normal MET CN (<2.3) median PDL1 expression was higher (50%) than in high MET CN (>=2.3: 37.5%; P=0.18). This translates into a significantly fewer number of high PD-L1 expressors (>49%) in cases with high MET CN (>2.2; P=0.06; Table). There was no significant difference in PDL1 expression between MET mutation vs. wild-type (P=0.9). Conclusions: PCs have high levels ofPD-L1 expression. There is an inverse relationship betweenMET CNand PD-L1 expression. This has implications when using checkpoint inhibitors for cases withMET copy number gain in NSCLC. Further evaluation is needed to better understand response to checkpoint inhibitors of PC cases withMETCNgain. (Table Presented) .