Abstract

Background: Central and peripheral location as well as thyroid transcription factor-I (TTF-1) expression was reported to be associated with different characteristics and prognosis of small-cell lung cancer (SCLC). This study aimed to investigate differential expression of PD-L1 in different SCLC subtypes, and in biopsy and resection specimens.Methods: We retrospectively analyzed 142 SCLC tumor samples using immunohistochemistry to correlate PD-L1 (22C3) expression with clinicopathologic features and survival data.Results: PD-L1 expression was found in 19.7% SCLCs (28/142) and was more frequent in females than in males (32%, 16/50 vs. 13%, 12/92, p = 0.009), in central type than in peripheral type SCLCs (26%, 26/100 vs. 4.8%, 2/42, p = 0.003), and in TTF-1 positive than in negative SCLCs (23.8%, 25/105 vs. 8.1%, 3/37, p = 0.039). PD-L1 expression was associated with vascular (p = 0.001) and lymphatic invasion (p = 0.001). There was no significant difference in PD-L1 expression between biopsy and resection specimens. On univariate analysis, patients with PD-L1 expression had significantly shorter progression-free survival (PFS; p = 0.026) and overall survival (OS; p = 0.012). Multivariate analysis revealed that PD-L1 expression was an independent prognostic factor for OS (HR, 2.317; 95% CI 1.199–4.478; p = 0.012) and PFS (HR, 1.636; 95% CI 0.990–2.703; p = 0.051) in SCLC.Conclusions: PD-L1 expression was more frequent in central type, TTF-1 positive SCLCs, and predicted a poor clinical outcome in these patients. Therefore, tumor location and TTF-1 expression could predict expression status of PD-L1, and could potentially serve as clinical response to immunotherapy.

Highlights

  • Small-cell lung cancer (SCLC) is an aggressive malignant disease with early development of metastasis

  • To address the above questions, we investigated the expression of PD-L1 in different types of SCLCs in terms of clinicopathologic characteristics and prognosis in this study, with the objective of finding more specific candidates for immunotherapy

  • Of the 54 resected SCLCs, eight cases were available with paired preoperative bronchoscopic biopsy specimens

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Summary

Introduction

Small-cell lung cancer (SCLC) is an aggressive malignant disease with early development of metastasis. The expression of PD-L1 on tumor cells has demonstrated good correlation with response in some clinical trials, but positive responses were only observed in a relatively small section of the patients with PD-L1 expression. Evidence suggests that patients with PD-L1–negative tumors may respond to immunotherapy [2, 5, 6]. This has prompted many researchers to seek out the subtype of patients who could benefit from immune treatments that has not yet been identified in SCLC. Central and peripheral location as well as thyroid transcription factor-I (TTF-1) expression was reported to be associated with different characteristics and prognosis of small-cell lung cancer (SCLC). This study aimed to investigate differential expression of PD-L1 in different SCLC subtypes, and in biopsy and resection specimens

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