Programmed cell death ligand 1 expression in cytologic and surgical non–small cell lung carcinoma specimens from a single institution: Association with clinicopathologic features and molecular alterations

Abstract

Background Programmed cell death ligand 1 (PD‐L1) expression by the 22C3 pharmDx companion assay has been validated in surgical specimens to support pembrolizumab treatment decisions for patients with non–small cell lung carcinoma (NSCLC). The aims of this study were 1) to assess the adequacy of cytologic specimens for PD‐L1 evaluation and 2) to explore correlations of PD‐L1 expression with clinicopathologic and molecular features. Methods The study cohort included 100 cytology specimens (fluid [n = 28] and fine‐needle aspiration [n = 72]) and 165 surgical specimens (biopsy [n = 138] and resection [n = 27]). The PD‐L1 immunohistochemistry 22C3 assay and staining assessment were performed according to the manufacturer's instructions. PD‐L1 expression was correlated with patients' demographics, pathologic characteristics, and molecular alterations. Results One hundred forty‐two specimens (53.6%) were positive for PD‐L1 expression (≥1%). No statistically significant difference in PD‐L1 expression was identified between cytologic (56.0%) and surgical specimens (52.1%). Seventy‐four of 190 tested cases (38.9%) had genetic alterations. PD‐L1 positivity was significantly more prevalent in cases with genetic alterations than in cases without genetic alterations. Furthermore, both PD‐L1 positivity and high PD‐L1 expression (≥50%) had statistically significant associations with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. PD‐L1 expression had no significant association with histologic phenotypes or other clinicopathologic features. Conclusions The data indicate that cytologic specimens are comparable to surgical specimens for PD‐L1 evaluation. The association of PD‐L1 expression with KRAS mutations may have clinical relevance in selecting patients with NSCLC for immunotherapy.

PD‐L1 expression in cell‐blocks of non‐small cell lung cancer: The impact of prolonged fixation

“…Developing a standardized procedure for cytological samples is undoubtedly challenging, since specimens can be fixed by a variety of methods and processed by different workflows. Moreover, although CBs can be prepared with distinct techniques, 18,30‐32 most studies applying PD‐L1 on cytology (Table 3) provide only few details on laboratory processing and fixation time 6‐9,11‐18 …”

“…Interestingly, 22 CBs have been included in the Blueprint (BP) PD‐L1 Immunohistochemistry Comparability Phase 2 Project, which aims to harmonize in real life practice the clinical use of different commercial PD‐L1 IHC assays on 81 routine lung cancer samples 5 . Noteworthy, several studies carried out on matched cytological and histological samples from the same patients have reported comparable results between CBs, surgical resections and small biopsy specimens in terms of adequacy rate, level of PD‐L1 expression, and clinical outcomes 6‐18 . Moreover, CBs also represent a valuable source of diagnostic material even in the early stages of the disease.…”

Interobserver agreement in programmed cell death‐ligand 1 immunohistochemistry scoring in nonsmall cell lung carcinoma cytologic specimens

“…Cell blocks were prepared from pellets of centrifuged cell suspension by adding plasma and thrombin to enmesh cellular materials using materials fixed in 10% neutral buffered formalin without any alcohol‐based prefixation. The details were described as before 16 . There was concomitant core biopsy in some cases, determined by procedure performing pulmonary physician based on the feasibility of performing a core biopsy.…”

PD-L1 in Cytological Samples: A Review and a Practical Approach

“…To establish whether cytological samples are as reliable as the histological samples for PD-L1 testing, numerous authors have intensively investigated the concordance rates between matched cytological and histological samples. Since 2017 several single institutional studies have reported comparable PD-L1 expression on matched cytological and histological (small biopsy/surgical resection) specimens (7,8,10,11,14,(37)(38)(39)(40)(41)(42)(43)(44).…”