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Aligning digital CD8 + scoring and targeted next‐generation sequencing with programmed death ligand 1 expression: a pragmatic approach in early‐stage squamous cell lung carcinoma
Author(s) -
Conde Esther,
Caminoa Alejandra,
Dominguez Carolina,
Calles Antonio,
Walter Stefan,
Angulo Barbara,
Sánchez Elena,
Alonso Marta,
Jimenez Luis,
Madrigal Luis,
Hernando Florentino,
SanzOrtega Julian,
Jimenez Beatriz,
Garrido Pilar,
PazAres Luis,
Castro Javier,
Hernandez Susana,
LopezRios Fernando
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13346
Subject(s) - immunohistochemistry , pd l1 , biology , tumor infiltrating lymphocytes , cancer research , microbiology and biotechnology , lung cancer , oncogene , context (archaeology) , cd8 , cancer , pathology , immune system , medicine , cell cycle , immunotherapy , immunology , genetics , paleontology
Aims To study programmed death ligand 1 ( PD ‐L1) expression, tumour‐infiltrating T lymphocytes ( TIL s) and the molecular context in patients with early‐stage squamous cell lung carcinomas ( SCC s). Methods and results The study included samples from 40 patients (discovery cohort) and 29 patients (validation cohort) diagnosed with early‐stage SCC . PD ‐L1 immunohistochemistry ( IHC ) was performed with three commercially available clones (E1L3N, SP 263 and SP 142). CD 8 + TIL s were scored with a digital algorithm. All tumours were analysed with targeted next‐generation sequencing ( NGS ). Additionally, TP 53 mutations were investigated with direct sequencing. In both cohorts, we observed a significant association between CD 8 + TIL s density and high PD ‐L1 IHC expression in tumour cells ( TC s). Furthermore, high SP 142 PD ‐L1 expression in immune cells ( IC s) was also associated significantly with CD 8 + TIL s density. Therefore, CD 8 + TIL s density discriminated between patients with high versus low PD ‐L1 IHC expression with excellent sensitivity and specificity. Interestingly, the highest percentages of PD ‐L1‐positive TC s with the three antibodies were found in samples with cyclin‐dependent kinase 6 ( CDK 6 ) amplification, with high amplification of proto‐oncogene C‐Myc ( CMYC ) or with cyclin D1– PI 3 kinase subunit alpha ( CCND 1– PIK 3 CA ) co‐amplification. High SP 142 PD ‐L1 IHC expression in IC s showed a non‐significant correlation with TP 53 mutations. Conversely, most cases with fibroblast growth factor receptor 1 ( FGFR 1 ) amplification were negative for all PD ‐L1 clones. Conclusions Our preliminary results support the use of digital CD 8 + TIL s scoring and targeted NGS alongside PD ‐L1 expression. The approach presented herein could help define patients with SCC s candidates to immune checkpoints inhibitors.