Factors Influencing Concordance of PD-L1 Expression between Biopsies and Cytological Specimens in Non-Small Cell Lung Cancer

Abstract

PD-L1 expression assessed by immunohistochemical staining is used for the selection of immunotherapy in non-small cell lung cancer (NSCLC). Appropriate validation of PD-L1 expression in cytology specimens is important as cytology is often the only diagnostic material in NSCLC. In a previous study comprising two different cohorts of paired biopsies and cytological specimens, we found a fairly good cyto-histological correlation of PD-L1 expression in one, whereas only a moderate correlation was found in the other cohort. Therefore, that cohort with additional new cases was now further investigated for the impact of preanalytical factors on PD-L1 concordance in paired biopsies and cytological specimens. A total of 100 formalin-fixed paraffin-embedded cell blocks from 19 pleural effusions (PE), 17 bronchial brushes (BB), and 64 bronchoalveolar lavage (BAL) and concurrent matched biopsies from 80 bronchial biopsies and 20 transthoracic core biopsies from NSCLC patients were stained using the PD-L1 28-8 assay. Using the cutoffs ≥1%, ≥5%, ≥10%, and ≥50% positive tumour cells, the overall agreement between histology and cytology was 77–85% (κ 0.51–0.70) depending on the applied cutoff value. The concordance was better for BALs (κ 0.53–0.81) and BBs (κ 0.55–0.85) than for PEs (κ −0.16–0.48), while no difference was seen for different types of biopsies or histological tumour type. A high number of tumour cells (>500) in biopsies was associated with better concordance at the ≥50% cutoff. In conclusion, the study results suggest that PEs may be less suitable for evaluation of PD-L1 due to limited cyto-histological concordance, while a high amount of tumour cells in biopsies may be favourable when regarding cyto-histological PD-L1 concordance.

Bronchoalveolar lavage fluid assessment facilitates precision medicine for lung cancer

“…Compared to peripheral blood, BALF is more proximal or “vicinal” to the tumor cells in the lung, so BALF can provide more direct information on the local immune status in lung tissue 13 . The detection of PD-L1 expression by cells derived from BALF is more consistent with paired tissue biopsies, which in turn is better than pleural effusion cells 25 . A tumor microenvironment analysis based on BALF showed that the expression of CXCL9 in BALF of NSCLC patients who responded to nivolumab is higher than non-responders 26 .…”

Comparative evaluation of PD‐L1 expression in cytology imprints, circulating tumour cells and tumour tissue in non‐small cell lung cancer patients

“…Many factors contribute to cytology–histology disagreement as well as to the heterogeneity in the reported agreement rates. This includes the intra‐tumour heterogeneity of PD‐L1 expression [ 26 ], the number of tumour cells in cytology samples [ 27 ] as well as the discordance due to the applied diagnostic tools in tumour sampling and staining procedures including used antibodies [ 28 ]. Further, the type of cytology specimens might have an impact as cytological cell blocks [ 29 , 30 , 31 ] which demonstrated better agreement with histology specimen than cytology imprints [ 14 , 32 , 33 ].…”

“…Many factors contribute to cytology-histology disagreement as well as to the heterogeneity in the reported agreement rates. This includes the intra-tumour heterogeneity of PD-L1 expression [26], the number of tumour cells in cytology samples [27] as well as the discordance due to the Table 3. Agreement between PD-L1 expression in tumour tissue biopsy (≥ 1 and ≥ 50% of tumour cells) and CTCs (n = 27).…”

Nationwide differences in cytology fixation and processing methods and their impact on interlaboratory variation in PD-L1 positivity

“…Our study only included cytological samples, many of which were not fixed in formalin or embedded in paraffin, which might explain the differences in results. Similarly, while some studies did not find a statistically significant association between PD-L1 expression and sampling site [49,50], comparable to our results (Table 1), others showed that pleural and nodal metastases were more likely to express PD-L1 than primary tumors [42]. Again, the difference in results could potentially be explained by the latter study using FFPE material which largely came from biopsies or surgical resections, while our study only used cytological material fixed and processed in a variety of ways.…”