Inter-relationship between PD-L1 expression and clinic-pathological features and driver gene mutations in pulmonary sarcomatoid carcinomas

Lococo, Filippo; Torricelli, Federica; Rossi, Giulio; Alifano, Marco; Damotte, Diane; Rapicetta, Cristian; Tamagnini, Ione; Cavazza, Alberto; Piana, Simonetta; Galeone, Carla; Paci, Massimiliano; Ciarrocchi, Alessia

doi:10.1016/j.lungcan.2017.09.009

Cited by 46 publications

(58 citation statements)

References 27 publications

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“…High expression of PD-L1 in PSC has been similarly noted in other studies. 101,131 The frequency of PD-L1 positive PSC samples is significantly higher than the one observed in NSCLC, coherently with higher presence of CD3+ or CD163+ infiltrating lymphocytes or macrophages observed in these tumors. 130 Together, these observations encourage the use of immunotherapy in the treatment of PSCs.…”

Section: Psc and Immunotherapymentioning

confidence: 61%

“…Last but not least, the encouraging preclinical success of KRASspecific inhibitors further consolidate the relevance of these mutations in the managing of these tumors. 100,101 MET exon 14 skipping mutations cause stabilization of MET protein leading to the constitutive activation of its signaling. 87 NSCLCs with activating alterations of MET (including MET locus amplification) have shown remarkable response to small molecules like crizotinib, cabozantinib or capmatinib that target MET activity.…”

Section: Clinical Impact Of Psc Molecular Profilingmentioning

confidence: 99%

“…In PSCs, several reports have investigated the expression of PD1 and/or PD-L1 to envisage a possible use of these therapies in this setting. 101,[123][124][125][126][127][128][129][130][131][132][133] Although widely employed and approved from different national drug agencies, 123 PD-L1 expression is an imperfect predictive biomarker for immunotherapy in lung cancer. PSC tends to show high levels of immunohistochemical expression with PD-L1, even if it is quite difficult to compare the data so far reported in literature in this histology.…”

Section: Psc and Immunotherapymentioning

confidence: 99%

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<p>Approaches to Tumor Classification in Pulmonary Sarcomatoid Carcinoma</p>

Baldovini¹,

Rossi²,

Ciarrocchi³

2019

LCTT

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Pulmonary sarcomatoid carcinoma (PSC) is a heterogeneous category of primary lung cancer accounting from 0.3% to 3% of all primary lung malignancies. According to the most recent 2015 World Health Organization (WHO) classification, PSC includes several different variants of malignant epithelial tumors (carcinomas) histologically mimicking sarcomas showing or entirely lacking a conventional component of non-small cell lung cancer (NSCLC). Thus, this rare subheading of lung neoplasms includes pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, pulmonary blastoma, and carcinosarcoma. A diagnosis of PSC may be suspected on small biopsy or cytology, but commonly requires a surgical resection to reach a conclusive definition. The majority of patients with PSC consists of elderly, smoking men with a large, peripheral mass characterized by well-defined margins. However, presentation with a central, polypoid endobronchial lesion is well-documented, particularly in pleomorphic carcinoma and carcinosarcoma showing a squamous cell carcinoma component. As expected, PSC may pose diagnostic problems and immunohistochemistry is largely used when pathologists deal these tumors in routine practice. Indeed, PSC tends to overexpress molecules associated with the epithelial-to-mesenchymal transition, such as vimentin, but the panel of immunostains also includes epithelial markers (cytokeratins, EMA), TTF-1, p40 and negative markers (e.g., melanocytic, mesothelial and sarcoma-related primary antibodies). Although rare, PSC has increased their interest among oncologist community for different reasons: a. identification of the epithelial-to-mesenchymal phenomenon as a major mechanism of secondary resistance to tyrosine kinase inhibitors; b. over-expression of PD-L1 and effective treatment with immunotherapy; c. identification of c-MET exon 14 skipping mutation representing an effective target to crizotinib and other specific inhibitors. In this review, the feasibility of the diagnosis of PSC, its differential diagnosis and novel molecular findings characterizing this group of lung tumor are discussed.

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Section: Psc and Immunotherapymentioning

confidence: 61%

Section: Clinical Impact Of Psc Molecular Profilingmentioning

confidence: 99%

Section: Psc and Immunotherapymentioning

confidence: 99%

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<p>Approaches to Tumor Classification in Pulmonary Sarcomatoid Carcinoma</p>

Baldovini¹,

Rossi²,

Ciarrocchi³

2019

LCTT

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“…Interestingly, several investigators have demonstrated that PSC often express a high level of PD-L1, ranging from 25% to 90% of cases and the expression is associated with poor prognosis. 7,8 In a series of surgically resected PSC cases, PD-L1 expression predicts nodal metastasis and early disease progression. 8 Evidence has begun to emerge regarding the efficacy of immunotherapy in PSC; however, most reports contain only a small number of patients, making it challenging to estimate the level of efficacy or to interpret the predictive value of PD-L1 expression.…”

Section: Introductionmentioning

confidence: 99%

Relationship Between Programmed Death Receptor-Ligand 1 Expression and Response to Checkpoint Inhibitor Immunotherapy in Pulmonary Sarcomatoid Carcinoma: A Pooled Analysis

Babacan

Piña

Signorelli

et al. 2020

Clinical Lung Cancer

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We performed a pooled analysis of published literature and institutional experience to understand the predictive value of programmed death receptor-ligand 1 expression on tumor response after checkpoint immunotherapy for pulmonary sarcomatoid carcinoma, a rare subtype of non-small cell lung cancer. As the level of programmed death receptor-ligand 1 expression increased, both tumor response and progression-free survival also significantly increased. Background: Pulmonary sarcomatoid carcinoma (PSC) or pleomorphic carcinoma is a rare subtype of non-small cell lung cancer. Some reports have suggested the efficacy of checkpoint inhibitor immunotherapy for PSC. However, owing to the small number of patients in each report, it remains unclear whether programmed death receptor-ligand 1 (PD-L1) expression is predictive of tumor response or survival. Patients and Methods: The English literature was systematically searched for articles published from 2015 to 2019 and reported on tumor response or progression-free survival (PFS) after immunotherapy for advanced PSC. In addition, our institutional electronic medical records were searched for eligible cases to be included. Pooled analyses were performed. Results: Analyses included 90 patients. Best tumor response was partial or complete response in 54.5%, stable disease 15.9%, and progressive disease in 29.6%. The median PFS was 7.0 months. Among 66 patients with reported PD-L1 expression, the level was <1% in 7 patients (10.6%), 1%-49% in 10 patients (15.2%), and 50% in 49 patients (74.2%). A positive relationship between PD-L1 level and tumor response was observed. Among 47 patients with a PD-L1 of 50%, 33 patients (70.2%) achieved response, compared with 5 of 10 patients (50%) with a PD-L1 of 1%-49% and 2 of 7 patients (28.6%) with a PD-L1 of <1% (P ¼ .026). PFS was superior among patients with a PD-L1 of 1% compared with those with a PD-L1 of <1% (14.4 months vs. 2.7 months respectively; P ¼ .04). Conclusions: Among patients with advanced PSC, PD-L1 expression is significantly associated with increased tumor responses and improved PFS after checkpoint inhibitor immunotherapy.

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“…Given 4 the rarity of sarcomatoid carcinoma there is sparse data on their genetic background. RAS mutations appear particularly prevalent, while targetable mutations are uncommon [14, [16][17][18][19][20]. Interestingly it was recently shown that MET gene mutations are relatively frequent in sarcomatoid carcinoma, in particular exon 14 skipping mutations are found which have been associated with favorable response to crizotinib therapy [21].…”

Section: Sarcomatoid Carcinoma Encompassing Spca Gcca and Plca -Morpmentioning

confidence: 99%