Research Article: PD-L1 expression in pleomorphic, spindle cell and giant cell carcinoma of the lung is related to TTF-1, p40 expression and might indicate a worse prognosis

Date Published: July 3, 2017

Publisher: Public Library of Science

Author(s): Violaine Yvorel, Arnaud Patoir, François Casteillo, Claire Tissot, Pierre Fournel, Marie-Laure Stachowicz, Georgia Karpathiou, Olivier Tiffet, Michel Péoc’h, Fabien Forest, Aamir Ahmad.

http://doi.org/10.1371/journal.pone.0180346

Abstract

Lung sarcomatoid carcinoma of the lung is a rare tumor with a poor prognosis. More than 90% of them are pleomorphic, spindle cell and giant cell carcinoma (PSCGCC). This rare subtype of lung cancer is thought to be more resistant to chemotherapy, and a small subset of them seems to exhibit targetable mutations. Immunotherapy against PD1/PDL-1 is a new emerging treatment, and might be of interest in PSGSCC because they frequently express PD-L1. The aim of our work is to evaluate PD1 and PDL-1 expression in a surgical series of lung PSCGCC and their relationship with morphological and immunohistochemical parameters and prognosis. Thirty-six patients who underwent surgical resection of a PSGSCC were included. PD-L1 (E1L3N) expression on tumor cells and PD1 (NAT105) expression by tumor infiltrating lymphocytes (TILs) were performed by immunohistochemistry. Results were compared to immunohistochemistry tests of TTF1, Napsin A, p40 and to molecular study of EGFR, KRAS, BRAF and HER2. Seventy-five % of PSCGCC were considered as positive for PD-L1.PD-L1 expression in PSGSCC is associated with TTF-1 and/or Napsin A expression (47.2%, p = 0.039). Few p40 positive PSCGCC expressed PD-L1 (8.3%, p = 0.013). PD1 expression was not related to TTF-1 and/or Napsin A expression (p = 0.47), p40 expression (p = 0.68) or survival (p = 0.14). PD-L1 or PD1 expression were not related to the age, gender, pT, pN, stage, visceral pleura invasion, histopathological subtype, the presence of giant cell component, the predominance of sarcomatoid component, and the presence of EGFR or BRAF or HER2 or PIK3CA mutation (p>0.05). PD-L1 expression was correlated with a worse overall survival in PSCGCC (p = 0.045). PD-L1 expression is frequent in PSCGCC and might be associated with the expression of adenocarcinoma markers (TTF-1, Napsin A) or the lack of expression of squamous cell carcinoma marker (p40).

Partial Text

Lung sarcomatoid carcinoma (SC) is a rare type of lung carcinoma with a poor prognosis, representing less than 1% of lung cancer. In the current 2015 WHO classification, 3 subtypes are recognized: pleomorphic, spindle cell, and giant cell carcinoma (PSCGCC), carcinosarcoma and pulmonary blastoma. More than 90% of SC is represented by PSCGCC. SC might be more resistant to chemotherapy and radiotherapy than other “non-small cell” lung carcinomas (NSCLC). We have recently showed that a subset of PSCGCC has a targetable mutation and might respond to targeted therapy [1]. Nevertheless, like other NSCLC, few PSCGCC have a targetable mutation. Recently, PD1/PD-L1 inhibitors were developed. For all the developed drugs, the consequence is an increased recognition of tumor cells by immune cells. In consequence, the survival is better, especially in patients positive for PD-L1 immunohistochemistry [2]. In NSCLC, PD-L1 expression is the highest in squamous cell carcinoma of smokers and is related to solid subtype and KRAS mutation in adenocarcinoma. In NSCLC, PD-L1 expression is found either higher in squamous cell carcinoma than in adenocarcinoma or higher in adenocarcinoma than in squamous cell carcinoma[10+ [ref D’inceco,]. A recent study has showed that PD-L1 expression is more frequent in SC than in NSCLC [3].

SC is thought to be more resistant than other NSCLC to chemotherapy and radiotherapy. A subset of SC harbors targetable mutations such as EGFR mutations, ALK or ROS 1 rearrangement. Immunotherapy targeting immune-checkpoint such as PD1/PD-L1 inhibitors might be of interest in this rare NSCLC subtype. PD-L1 expression in our study is high: from 53 to 90.2% as described in other studies [3,6–10]. PD-L1 expression in SC was found higher than in NSCLC in the same center with the same antibody and cutoff [3]. In NSCLC, PD-L1 immunohistochemistry has emerged as a biomarker predicting which patients are more likely to respond to PD/PD-L1 blockade. The best clone to use or which threshold for positivity are still subject to discussions, and some differences between studies might be explained by the different protocols used [11].

 

Source:

http://doi.org/10.1371/journal.pone.0180346

 

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