Cytologic‐histologic correlation of programmed death‐ligand 1 immunohistochemistry in lung carcinomas

Russell‐Goldman, Eleanor; Kravets, Sasha; Dahlberg, Suzanne E.; Sholl, Lynette M.; Vivero, Marina

doi:10.1002/cncy.21973

Cited by 84 publications

(94 citation statements)

References 30 publications

(89 reference statements)

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“…To date, only a limited number of publications have studied the consistency and accuracy of PD‐L1 evaluation by investigating the interobserver agreement on PD‐L1 scoring among pathologists. Most studies focused exclusively on NSCLC, while only two studies included HSCC, one included UC and none included for BC . Table provides a literature review of these studies.…”

Section: Discussionmentioning

confidence: 99%

Inter‐ and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma

et al. 2019

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Aims Programmed death‐ligand 1 (PD‐L1) expression by tumour cells (TC) is a mechanism for tumour immune escape through down‐regulation of antitumour T cell responses and is a target for immunotherapy. PD‐L1 status as a predictor of treatment response has led to the development of multiple biomarkers with different reference cut‐offs. We assessed pathologist consistency in evaluating PD‐L1 immunopositivity by examining the inter‐ and intraobserver agreement using various antibody clones and different cancer types. Methods and results PD‐L1 expression in TC and immune cells (IC) was manually scored in 27 head and neck squamous cell carcinoma (HSCC), 30 urothelial carcinoma (UC) and breast carcinoma (BC) using three commercial clones (SP263, SP142, 22C3) and one platform‐independent test (E1L3N). For interobserver agreement, PD‐L1 status was evaluated blindly by three pathologists. For intraobserver agreement, PD‐L1 expression was re‐evaluated following a wash‐out period. Intraclass correlation coefficient (ICC), overall percentage agreement (OPA) and κ‐values were calculated. Using clinical algorithms, the percentage of PD‐L1‐positive cases in HSCC, BC and UC were 15–81%, 47–67% and 7–43%, respectively. The percentage of PD‐L1 positive cases relied heavily on the algorithm/cut‐off values used. Almost perfect interobserver agreement was achieved using SP263 and E1L3N in HSCC, 22C3, SP142 and E1L3N in BC and 22C3 in UC. The SP142 clone in UC and HSCC showed moderate agreement and was associated with lower ICC and decreased intraobserver concordance. Conclusions Excellent inter‐ and intraobserver agreement can be achieved using SP263, 22C3 and E1L3N, whereas PD‐L1 scoring using SP142 clone is associated with a higher level of subjectivity.

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Section: Discussionmentioning

confidence: 99%

Inter‐ and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma

et al. 2019

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“…Moreover, anti–PD‐L1 and anti–PD‐1 monoclonal antibody therapies have shown promising and valid results in treating several cancers . Notably, none of the FDA‐approved PD‐L1 antibodies have been validated on cytologic samples, despite the finding that PD‐L1 testing by IHC is reasonable in different cytologic preparations . Recent publications dealing with lung cytologic samples have demonstrated the feasibility of PD‐L1 staining and high concordance with matching histologic samples, so that it might be useful for selecting appropriate patients for immunotherapy even in a presurgical phase of evaluation.…”

Section: Discussionmentioning

confidence: 99%

“…Instead, the majority of studies to date have dealt with the use of FFPE cytology cell blocks (CBs). Nonetheless, a few authors have demonstrated that PD‐L1 expression still can be performed on conventional cytology samples . However, limitations in this setting include nonspecific nuclear and cytoplasmic positivity, high background staining, difficulty evaluating 3‐dimensional cellular clusters, and the high number of false‐negative interpretations.…”

Section: Introductionmentioning

confidence: 99%

PD‐L1 and thyroid cytology: A possible diagnostic and prognostic marker

Dell’Aquila

Granitto

Martini

et al. 2019

Cancer Cytopathology

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Background Programmed death‐ligand 1 (PD‐L1) expression is emerging as an important predictive biomarker in anti–PD‐L1 cancer immunotherapy. Its role has been clearly defined in various human cancers and is linked to a poor prognosis and resistance to anticancer therapies. The role of PD‐L1 in thyroid cancers has not been well defined in fine‐needle aspiration cytology (FNAC). The authors examined the performance of PD‐L1 immunostaining in liquid‐based cytology (LBC) to determine whether it could be a biomarker of malignancy or aggressive disease. Methods From January 2018 to March 2019, 236 thyroid lesions, which had been diagnosed by FNAC as indeterminate lesions, suspicious for malignancy (SFM), and malignant, were enrolled. PD‐L1 immunostaining was performed on both LBC and corresponding histology samples. Results The FNAC cohort included 50 benign negative controls, 42 samples of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 33 samples of follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 53 samples that were suspicious for malignancy (SFM), and 58 malignant samples. AUS/FLUS samples included 3 goiters, 32 follicular adenomas (FAs), 1 noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP), 5 invasive follicular variants of papillary thyroid carcinoma (I‐FVPTCs), and 1 follicular carcinoma; whereas FN/SFN samples included 24 FAs and 9 malignancies (4 I‐FVPTCs, 1 NIFTP, 3 papillary thyroid carcinomas [PTCs], and 1 oncocytic follicular carcinoma). The 53 SFM samples were diagnosed on histopathology as 2 FAs, 5 NIFTPs, 15 I‐FVPTCs, and 31 PTCs; whereas the 58 malignant specimens included 5 NIFTPs, 5 I‐FVPTCs, and 48 PTCs. Increased plasma membrane and cytoplasmic PD‐L1 expression was found in 79 cases (38.5%), including 61 PTCs (conventional and variants). Negative PD‐L1 expression was found in NIFTPs and FAs. A BRAF V600E mutation was identified in 15% of PD‐L1–positive malignancies. Conclusions The current data suggest that PD‐L1 expression in the thyroid gland might represent a marker of malignancy that correlates with PTC, but not with NIFTP. Thyroid neoplasms with PD‐L1 expression also ae enriched with BRAF V600E mutations, suggesting that they are associated with more aggressive behavior.

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“…However, cytology specimens are often the only materials available, especially for patients at an advanced stage. Limited studies have compared PD‐L1 IHC on cytologic specimens and surgical specimens, and most of them had small study cohorts with PD‐L1 IHC not performed as part of routine clinical care . Our study addressed the comparability of PD‐L1 IHC on cytologic specimens and surgical specimens in a large cohort of clinical cases (265 clinical cases, including 100 cytologic specimens and 165 surgical specimens).…”

Section: Discussionmentioning

confidence: 99%

“…Most studies have evaluated PD‐L1 expression in surgical specimens, and studies of cytology specimens are limited . However, cytologic specimens are frequently the only specimens available, especially for patients at an advanced stage.…”

Section: Introductionmentioning

confidence: 99%

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

Mei

Shilo

Wei

et al. 2019

Cancer Cytopathology

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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.

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Cytologic‐histologic correlation of programmed death‐ligand 1 immunohistochemistry in lung carcinomas

Cited by 84 publications

References 30 publications

Inter‐ and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma

Inter‐ and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma

PD‐L1 and thyroid cytology: A possible diagnostic and prognostic marker

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

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