Histomolecular profiling of pleomorphic, spindle cell, and giant cell carcinoma of the lung for targeted therapies

Forest, Fabien; Yvorel, Violaine; Karpathiou, Georgia; Stachowicz, Marie-Laure; Vergnon, Jean‐Michel; Fournel, P.; Tiffet, Olivier; Trombert, Béatrice; Péoc’h, Michel

doi:10.1016/j.humpath.2015.10.006

Cited by 33 publications

(18 citation statements)

References 33 publications

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“…Patients were staged according to the current TNM staging (7 th Edition). Clinical data, histopathological data, p40 (polyclonal, dilution 1:75, Clinisciences, Nanterre France), Napsin A (clone IP64, dilution 1:400, Novocastra, Nanterre France) and TTF-1 (clone: 8G7G3/1, dilution 1:50, Dako, Courtaboeuf France) immunohistochemistry, and molecular data for most patients were taken from a previous publication of our group [1]. …”

Section: Methodsmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

“…We previously suggested that the presence of molecular targets in PSCGCC might be related to their morphological or immunohistochemical differentiation [1]. Nevertheless, the relationship between PD-L1 and PD1 expression and morphological differentiation or immunohistochemical factors have not been studied in PSCGCC.…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2017

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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).

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

et al. 2017

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“…However, the efficacy of gefitinib is limited in patients with pulmonary sarcomatoid carcinoma harbouring EGFR mutations. Although few studies have described the genetic features of lung spindle cell carcinomas , a previous report noted that EGFR mutations were detected in 8.8% of patients with pulmonary sarcomatoid carcinoma, but the response to EGFR‐TKIs was poor and transient in these patients . Other genomic alterations in pulmonary sarcomatoid carcinoma include tumour protein p53 (TP53; 73.6%), cyclin‐dependent kinase inhibitor 2A (CDKN2A; 37.6%), KRAS (34.4%), cyclin‐dependent kinase inhibitor 2B (CDKN2B; 23.2%), and neurofibromin 1 (NF1; 17.6%) .…”

Section: Discussionmentioning

confidence: 99%

Lung spindle cell carcinoma harbouring a constitutively active epidermal growth factor receptor mutation

Ikushima

Sakatani

Morikawa

et al. 2018

Respirology Case Reports

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Lung spindle cell carcinoma is a rare lung tumour with a poor prognosis, and its standard therapy has not been established. Furthermore, little work has been conducted on the genetic characteristics of lung spindle cell carcinomas. Here, we report an 82‐year‐old woman who was referred to our hospital due to a fever and dyspnoea. Chest computed tomography demonstrated a 75‐mm mass surrounded by infiltrates and atelectasis in the right upper lobe. She was eventually diagnosed with lung spindle cell carcinoma corresponding to clinical stage IVB (cT4N2M1c(ADR)). A genetic study indicated that epidermal growth factor receptor (EGFR) exon 19 was deleted in the tumour cells. She received gefitinib as first‐line therapy. However, no significant effect was observed, and she died of respiratory failure 89 days after the initial admission. To our knowledge, this is the first case of spindle cell carcinoma of the lung in which a sensitizing EGFR mutation is detected.

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“… 15 In contrast, three studies did not detect ALK rearrangements in 35 and 14 patients with PPC or 41 patients with PSC. 18 – 20 …”

Section: Discussionmentioning

confidence: 99%

Anaplastic lymphoma kinase (ALK)-rearranged pulmonary pleomorphic carcinoma successfully treated with crizotinib

et al. 2018

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Pulmonary pleomorphic carcinoma (PPC) is rare, and the response of patients to conventional chemotherapy is very poor. Here we present a patient with anaplastic lymphoma kinase (ALK)-rearranged advanced PPC treated with crizotinib. Computed tomography revealed a mass in the left upper lung of a nonsmoking 60-year-old woman. Pathological findings using resected tissue were consistent with PPC stage 1A, T1bN0M0. Although the patient received adjuvant radiotherapy, the disease relapsed, quickly progressed, and remained PPC according to analysis of biopsied tissue. Although negative for epidermal growth factor receptor mutations, ALK rearrangements were detected in adenocarcinoma and spindle-cell components. The patient received crizotinib therapy and achieved a partial response for 7 months. This case indicates that patients with PPC, particularly those with adenocarcinoma, may harbor an epithelial component with the ALK rearrangement. Although the progression-free survival of patients treated with crizotinib is limited, they may obtain more benefit compared with conventional chemotherapy.

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Histomolecular profiling of pleomorphic, spindle cell, and giant cell carcinoma of the lung for targeted therapies

Cited by 33 publications

References 33 publications

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

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

Lung spindle cell carcinoma harbouring a constitutively active epidermal growth factor receptor mutation

Anaplastic lymphoma kinase (ALK)-rearranged pulmonary pleomorphic carcinoma successfully treated with crizotinib

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