Cell-blocks are suitable material for programmed cell death ligand-1 immunohistochemistry: Comparison of cell-blocks and matched surgical resection specimens in lung cancer

Min Gyoung Pak, Mee Sook Roh, Min Gyoung Pak, Mee Sook Roh

Abstract

Objective: Programmed cell death ligand-1 (PD-L1) has emerged as a predictive biomarker in lung cancer. PD-L1 immunohistochemistry (IHC) assay predicts the response to immunotherapy, but cytology specimens are often the only samples available in a considerable proportion of advanced lung cancer patients. We delineate practical feasibility and efficacy of cytology cell-block (CB) specimens for PD-L1 expression and concordance between cytology CBs and surgical resection specimens.

Methods: In total, 58 eligible patients with primary lung cancer who received computed tomography-guided percutaneous needle aspiration and surgery were included. PD-L1 IHC (clone SP263) was performed on CBs prepared from residual liquid-based cytology material and matched surgical resection specimens. PD-L1 positive tumour cell proportion was categorised in four score groups: (a) <1%; (b) ≤1% to <10%; (c) ≤10% to <50%, (d) ≥50%.

Results: Comparison of PD-L1 expression in cytology CBs and matched surgical resection specimens showed a high concordance (κ value 0.65). According to the therapeutic guideline of immunotherapeutic agents, a positive percent agreement was 94.34%, and a negative percent agreement was 100% at a cut-off value for positivity of 1% PD-L1 expression. There was a significant difference observed with regard to rates of PD-L1 positivity when comparing smoking history (P = 0.02), age (P = 0.04) and pathological TNM stage (P = 0.04).

Conclusions: The results show that cytology CBs evaluated for PD-L1 IHC assay have high concordance with matched surgical resection specimens and can be used for assessing PD-L1 expression. Also, we propose that CBs are suitable materials for evaluating PD-L1 expression while simultaneously performing both diagnostic and molecular tests.

Keywords: cell-blocks; cytology; immune checkpoint therapy; lung cancer; matched surgical resection specimens; programmed cell death ligand-1.

Conflict of interest statement

The authors have no conflicts of interest to report.

© 2019 The Authors. Cytopathology Published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Programmed cell death ligand‐1 (PD‐L1) immunohistochemical staining on cytology cell blocks and matched histology slides (A and B) Case 1. The cytology cell block (A) and matched histology (B) slides showed no PD‐L1 positive tumour cells (×100; C and D) Case 2. Both slides showed more than 1%, but less than 10% PD‐L1 positivity in adenocarcinoma. (×100; E and F) Case 3. Squamous cell carcinoma showed more than 1%, but less than 10% PD‐L1 positivity in cytology and histology slides (×100; G and H) Case 4. High PD‐L1 expression, more than 50%, was observed in G and H (G: ×100, H: ×40)
Figure 2
Figure 2
The only case of substantial PD‐L1 discrepancy (A) The cytology CB specimen showed less than 1% PD‐L1 positivity. (x40) (B) The matched surgical resection specimen from the same patient showed heterogeneous PD‐L1 positivity. The final score was 2. (x10) (C) The high magnification view of dashed line circle in Figure 2(B) showed less than 1% PD‐L1 positivity, the same PD‐L1 result of the cytology CB specimen. (x100) (D) The high magnification view of solid line circle in Figure 2(B) showed near 80% PD‐L1 positivity, the discordant PD‐L1 result of the cytology CB specimen. (x100)

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7‐30.
    1. Hirsch FR, Scagliotti GV, Mulshine JL, et al. Lung cancer: current therapies and new targeted treatments. Lancet. 2017;389(10066):299‐311.
    1. Remon J, Steuer CE, Ramalingam SS, Felip E. Osimertinib and other third‐generation EGFR TKI in EGFR‐mutant NSCLC patients. Ann Oncol. 2018;29(suppl_1):i20‐i27.
    1. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD‐L1‐positive, advanced non‐small‐cell lung cancer (KEYNOTE‐010): a randomised controlled trial. Lancet. 2016;387(10027):1540‐1550.
    1. Reck M, Rodriguez‐Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD‐L1‐positive non‐small‐cell lung cancer. N Engl J Med. 2016;375(19):1823‐1833.
    1. Borghaei H, Paz‐Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non‐small‐cell lung cancer. N Engl J Med. 2015;373(17):1627‐1639.
    1. Fehrenbacher L, Spira A, Ballinger M, et al. Atezolizumab versus docetaxel for patients with previously treated non‐small‐cell lung cancer (POPLAR): a multicentre, open‐label, phase 2 randomised controlled trial. Lancet. 2016;387(10030):1837‐1846.
    1. Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379(24):2342‐2350.
    1. Patel SP, Kurzrock R. PD‐L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14(4):847‐856.
    1. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non‐small‐cell lung cancer. N Engl J Med. 2015;372(21):2018‐2028.
    1. Rizvi NA, Mazieres J, Planchard D, et al. Activity and safety of nivolumab, an anti‐PD‐1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non‐small‐cell lung cancer (CheckMate 063): a phase 2, single‐arm trial. Lancet Oncol. 2015;16(3):257‐265.
    1. Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti‐PD‐L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563‐567.
    1. Kerr KM, Bubendorf L, Edelman MJ, et al. Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non‐small‐cell lung cancer. Ann Oncol. 2014;25(9):1681‐1690.
    1. Leighl NB, Rekhtman N, Biermann WA, et al. Molecular testing for selection of patients with lung cancer for epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists/International Association for the study of lung cancer/association for molecular pathology guideline. J Clin Oncol. 2014;32(32):3673‐3679.
    1. Jain D, Mathur SR, Iyer VK. Cell blocks in cytopathology: a review of preparative methods, utility in diagnosis and role in ancillary studies. Cytopathology. 2014;25(6):356‐371.
    1. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10(9):1243‐1260.
    1. Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest. 2009;136(1):260‐271.
    1. Marchetti A, Barberis M, Franco R, et al. Multicenter comparison of 22C3 PharmDx (Agilent) and SP263 (Ventana) assays to test PD‐L1 expression for NSCLC patients to be treated with immune checkpoint inhibitors. J Thorac Oncol. 2017;12(11):1654‐1663.
    1. Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer. 2005;5(4):263‐274.
    1. Tang F, Zheng P. Tumor cells versus host immune cells: whose PD‐L1 contributes to PD‐1/PD‐L1 blockade mediated cancer immunotherapy? Cell Biosci. 2018;8:34. eCollection 2018.
    1. McLaughlin J, Han G, Schalper KA, et al. Quantitative assessment of the heterogeneity of PD‐L1 expression in non‐small‐cell lung cancer. JAMA Oncol. 2016;2(1):46‐54.
    1. Capizzi E, Ricci C, Giunchi F, et al. Validation of the immunohistochemical expression of programmed death ligand 1 (PD‐L1) on cytological smears in advanced non small cell lung cancer. Lung Cancer. 2018;126:9‐14.
    1. Rimm DL, Han G, Taube JM, et al. A prospective, multi‐institutional, pathologist‐based assessment of 4 immunohistochemistry assays for PD‐L1 expression in non‐small cell lung cancer. JAMA Oncol. 2017;3(8):1051‐1058.
    1. Hirsch FR, McElhinny A, Stanforth D, et al. PD‐L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD‐L1 IHC assay comparison project. J Thorac Oncol. 2017;12(2):208‐222.
    1. Nakamura Y, Kobayashi T, Nishii Y, et al. Comparable immunoreactivity rates of PD‐L1 in archival and recent specimens from non‐small cell lung cancer. Thorac Cancer. 2018;9(11):1476‐1482.
    1. Russell‐Goldman E, Kravets S, Dahlberg SE, Sholl LM, Vivero M. Cytologic‐histologic correlation of programmed death‐ligand 1 immunohistochemistry in lung carcinomas. Cancer Cytopathol. 2018;126(4):253‐263.
    1. Heymann JJ, Bulman WA, Swinarski D, et al. PD‐L1 expression in non‐small cell lung carcinoma: comparison among cytology, small biopsy, and surgical resection specimens. Cancer Cytopathol. 2017;125(12):896‐907.
    1. Noll B, Wang WL, Gong Y, et al. Programmed death ligand 1 testing in non‐small cell lung carcinoma cytology cell block and aspirate smear preparations. Cancer Cytopathol. 2018;126(5):342‐352.
    1. Skov BG, Skov T. Paired comparison of PD‐L1 expression on cytologic and histologic specimens from malignancies in the lung assessed with PD‐L1 IHC 28‐8pharmDx and PD‐L1 IHC 22C3pharmDx. Appl Immunohistochem Mol Morphol. 2017;25(7):453‐459.
    1. Jain D, Sukumar S, Mohan A, Iyer VK. Programmed death‐ligand 1 immunoexpression in matched biopsy and liquid‐based cytology samples of advanced stage non‐small cell lung carcinomas. Cytopathology. 2018;29(6):550‐557.
    1. Cho JH, Sorensen SF, Choi YL, et al. Programmed death ligand 1 expression in paired non‐small cell lung cancer tumor samples. Clin Lung Cancer. 2017;18(6):e473‐e479.
    1. Hernandez A, Brandler TC, Zhou F, Moreira AL, Schatz‐Siemers N, Simsir A. Assessment of programmed death‐ligand 1 (PD‐L1) immunohistochemical expression on cytology specimens in non‐small cell lung carcinoma. Am J Clin Pathol. 2019;151(4):403‐415.
    1. Kim MY, Koh J, Kim S, Go H, Jeon YK, Chung DH. Clinicopathological analysis of PD‐L1 and PD‐L2 expression in pulmonary squamous cell carcinoma: comparison with tumor‐infiltrating T cells and the status of oncogenic drivers. Lung Cancer. 2015;88(1):24‐33.
    1. Xu H, Bratton L, Nead M, Russell D, Zhou Z. Comparison of programmed death‐ligand 1 (PD‐L1) immunostain for nonsmall cell lung carcinoma between paired cytological and surgical specimens. Cytojournal. 2018;15:29.
    1. Stampfli MR, Anderson GP. How cigarette smoke skews immune responses to promote infection, lung disease and cancer. Nat Rev Immunol. 2009;9(5):377‐384.
    1. Kinoshita T, Muramatsu R, Fujita T, et al. Prognostic value of tumor‐infiltrating lymphocytes differs depending on histological type and smoking habit in completely resected non‐small‐cell lung cancer. Ann Oncol. 2016;27(11):2117‐2123.
    1. Calles A, Liao X, Sholl LM, et al. Expression of PD‐1 and its ligands, PD‐L1 and PD‐L2, in smokers and never smokers with KRAS‐mutant lung cancer. J Thorac Oncol. 2015;10(12):1726‐1735.
    1. Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD‐1 blockade in non‐small cell lung cancer. Science. 2015;348(6230):124‐128.
    1. Sun JM, Zhou W, Choi YL, et al. Prognostic significance of PD‐L1 in patients with non‐small cell lung cancer: a large cohort study of surgically resected cases. J Thorac Oncol. 2016;11(7):1003‐1011.
    1. Schmidt LH, Kummel A, Gorlich D, et al. PD‐1 and PD‐L1 expression in NSCLC indicate a favorable prognosis in defined subgroups. PLoS ONE. 2015;10(8):e0136023.
    1. Cooper WA, Tran T, Vilain RE, et al. PD‐L1 expression is a favorable prognostic factor in early stage non‐small cell carcinoma. Lung Cancer. 2015;89(2):181‐188.
    1. Mu CY, Huang JA, Chen Y, Chen C, Zhang XG. High expression of PD‐L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med Oncol. 2011;28(3):682‐688.

Source: PubMed

3
S'abonner