Alternative sources of tumour information need to be explored in patients with non‐small cell lung cancer (NSCLC). Here, we compared programmed cell death ligand 1 (
PD‐L1
) expression on cytology imprints and circulating tumour cells (CTCs) with PD‐L1 tumour proportion score (TPS) from immunohistochemistry staining of tumour tissue from patients with NSCLC. We evaluated
PD‐L1
expression using a PD‐L1 antibody (28‐8) in representative cytology imprints, and tissue samples from the same tumour. We report good agreement rates on PD‐L1 positivity (TPS ≥ 1%) and high
PD‐L1
expression (TPS ≥ 50%). Considering high
PD‐L1
expression, cytology imprints showed a PPV of 64% and a NPV of 85%. CTCs were detected in 40% of the patients and 80% of them were PD‐L1
+
. Seven patients with
PD‐L1
expression of < 1% in tissue samples or cytology imprints had PD‐L1
+
CTCs. The addition of
PD‐L1
expression in CTCs to cytology imprints markedly improved the prediction capacity for PD‐L1 positivity. A combined analysis of cytological imprints and CTCs provides information on the tumoural PD‐L1 status in NSCLC patients, which might be used when no tumor tissue is available.
Objectives
The majority of lung cancer cases are of advanced stage and diagnosis is usually made using minimally invasive small biopsies and cytological specimens. The WHO 2015 classification recommends limiting immunocytochemistry (ICC) to lung cancer typing and molecular testing drives for personalised therapies. An algorithm using Bayes' theorem could be useful for defining antibody profiles. This study aims to assess the impact of different antibody profiles for cytological samples on the accuracy of lung cancer typing with a large‐scale Bayesian analysis.
Methods
A retrospective examination of 3419 consecutive smears and/or cytospins diagnosed over 2011‐2016 found 1960 primary lung cancer tumours: 972 adenocarcinomas (ADC), 256 squamous carcinomas (SQC), 268 neuroendocrine tumours (NET), and 464 non‐small cell cancer‐not otherwise specified (NSCC‐NOS). The a priori and a posteriori probabilities, before and after ICC using antibodies singly or in combination, were calculated for different lung cancer types.
Results
TTF‐1 or CK7 alone improved the a posteriori probabilities of correct cytological typing for ADC to 86.5% and 95.8%, respectively. For SQC, using p40 (∆Np63) or CK5/6 together with CK5/14 led to comparable results (78.3% and 90.3%). With synaptophysin or CD56 alone, improvements in a posteriori probabilities to 87.5 and 90.3% for the correct recognition of NET could be achieved.
Conclusions
Based on morphological and clinical data, the use of two antibodies appears sufficient for reliable detection of the different lung cancer types. This applies to diagnoses that were finalised following ICC both on a clinical or cytological basis and on a histological basis.
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