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PD-L1 Expression in Small Cell and Large Cell Neuroendocrine Carcinomas of Lung: an Immunohistochemical Study with Review of Literature

  • Original Article
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Pathology & Oncology Research

Abstract

High-grade neuroendocrine tumors (HGNET) have distinctive tumor biology/behaviour. Newer modalities of treatment (immunotherapy) for them have been included in recent NCCN guidelines. Detection of programmed death receptor-ligand 1 (PD-L1) expression by immunohistochemistry have made easy identification of patients eligible for immunotherapy. We aimed to ascertain expression of PD-L1 on small cell and large cell neuroendocrine carcinomas of lung and review existing literature. Eighty-five cases of HGNET lung (primary/metastatic), were retrieved and reviewed. Immunostaining for PD-L1 using clone SP263 was done. Any amount/intensity of membranous staining of > = 1% tumor cells was cut-off for positivity. Previously published studies using Google and/Pubmed search engines were reviewed. Of 85 cases, 70 were small-cell lung cancer (SCLC), 11 large-cell neuroendocrine carcinoma (LCNEC) and 4 combined SCLC. Median age was 46.5 years with male preponderance. No PD-L1 expression was seen in 91.6% cases. The 7 positive cases were 4 LCNEC, 2 SCLC and 1 combined SCLC. The percentage positivity varied from 1–100%; lower percentage positivity was seen in SCLC. PD-L1 expression on immune cells was seen in 31.3% cases. Sixteen studies evaluating 1992 NET were found; E1L3N PD-L1 clone was commonly used clone. PD-L1 positivity was associated with better prognosis in most studies. There are only a few studies available in literature related to PDL1 expression in high grade neuroendocrine carcinomas of lung. In general, PD-L1 positivity is highly variable and seen in lower percentage of these tumors. With the recent approval of immunotherapy, biomarkers other than PD-L1 should also be investigated in these tumors.

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Funding

The work is funded by DST-SERB CRG/2018/003722.

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Authors and Affiliations

  1. Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

    Prerna Guleria

  2. Department of Surgical Oncology, Dr BRA Institute-Rotary Cancer Hospital All India Institute of Medical Sciences, New Delhi, 110029, India

    Sunil Kumar

  3. Department of Medical Oncology, Dr BRA Institute-Rotary Cancer Hospital All India Institute of Medical Sciences, New Delhi, 110029, India

    Prabhat Singh Malik

  4. Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India

    Deepali Jain

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Prerna Guleria], [Sunil Kumar], Prabhat Singh Malik and [Deepali Jain]. The first draft of the manuscript was written by [Prerna Guleria] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Deepali Jain.

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Guleria, P., Kumar, S., Malik, P.S. et al. PD-L1 Expression in Small Cell and Large Cell Neuroendocrine Carcinomas of Lung: an Immunohistochemical Study with Review of Literature. Pathol. Oncol. Res. 26, 2363–2370 (2020). https://doi.org/10.1007/s12253-020-00832-0

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