PD-L1 expression on routine samples of non-small cell lung cancer: results and critical issues from a 1-year experience of a centralised laboratory

Abstract

<jats:sec><jats:title>Aims</jats:title><jats:p>Our laboratory is a centralised centre receiving routine non-small cell lung cancer (NSCLC) samples for programmed death ligand-1 (PD-L1) immunohistochemical (IHC) evaluation. Since literature data are not concordant here we review our clinical records to assess the rate of PD-L1 positive and negative NSCLC cases in real-world practice.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>PD-L1 expression was evaluated by a validated 22C3 IHC laboratory developed test on 211 prospectively collected routine NSCLC samples, received from 10 outside institutions. PD-L1 expression was assessed by the tumour proportion score (TPS) and reported by using a three cut-point system: TPS&lt;1, TPS 1%–49% and TPS≥50%.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Overall, 193 out of 211 samples (91.5%) meet the criteria for adequacy (more than 100 viable neoplastic cells). In 62.7% (121/193) of samples TPS was &lt;1%; 17.6% of samples (34/193) expressed PD-L1 with a TPS of 1%–49% and 19.7% (38/193) with a TPS of &gt;50%. There was no significant difference in PD-L1 expression rates between different histotypes and site of sampling. Instead, a statistically significant difference was associated to the type of samples: in fact, cytological samples were more frequently negative for PD-L1 expression (TPS&lt;1%) and less often displayed PD-L1 expression at high levels (TPS&gt;50%) than surgical resections and biopsies.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>We present a referral laboratory experience on IHC PD-L1 expression of prospectively collected routine NSCLC samples. Data from the real-world practice can better clarify the percentage of PD-L1 positive and negative cases, to establish benchmarks for good practice standards.</jats:p></jats:sec>

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

“…For example, our large referral center often receives direct smears for EGFR and BRAF DNA‐based mutational testing and material suspended in formalin for CB preparation and PD‐L1 testing from cytopathologists and/or clinicians working in peripheral institutions or hospitals. Indeed, we recently showed that, as opposed to surgical resections and histological biopsies, CBs outsourced from different institutions very frequently lack PD‐L1 expression and scarcely display high levels of PD‐L1 expression 22 . These observations clearly suggest that standardization of fixation time is critical for specimen preservation and reliable test results.…”

“…PD‐L1 ICC was carried out with two different assays: (a) a validated laboratory developed test (LDT) based on concentrated DAKO 22C3 anti‐PDL1 primary antibody (Dako, Carpinteria, California) performed with Ventana's detection systems on the BenchMark XT platform (Ventana, Tucson, Arizona) 22 ; (b) the companion diagnostic kit SP263 assay (Ventana), following the manufacturer's instructions.…”

“…We maintain that this issue deserves investigation considering that our centralized laboratory practice analyses lung cancer biomarkers in NSCLC samples coming either form different peripheral institutions or from different regions of southern Italy. In fact, in our experience, cytological samples outsourced from different institutions and processed with a validated 22C3 laboratory developed test (LDT) are more frequently negative for PD‐L1 expression and less frequently positive for high levels of PD‐L1 expression than surgical resections and biopsies 22 . We hypothesized that this discrepancy might be due to the variable length of fixation time adopted by various institutions.…”

Predictive molecular pathology in the time of COVID-19

“…During the COVID-19 outbreak, the laboratory kept performing predictive molecular testing on tumour tissue specimens. [5][6][7][8] However, laboratory organisation needed to be completely reshaped to limit personnel number and working hours. Before the COVID-19 outbreak, our laboratory adopted, in most cases, laboratorydeveloped tests (LDTs).…”

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

“…T‐cell exhaustion due to binding of PD‐1 and PD‐L1 induces immune evasion of cancer cells from anti‐cancer immune responses . The percentage of PD‐L1‐positivity in cancer cells, named the tumor proportion score (TPS), is also considered a predictive biomarker for anti‐PD‐1/PD‐L1 therapy in lung cancer . Several monoclonal antibodies such as 22C3, 28‐8, SP263, and SP142 have been used for immunohistochemistry (IHC) to detect PD‐L1 expression, and clones 22C3 and SP142 are now available for companion and complementary diagnostics .…”