Thibault Vieira1, Martine Antoine2, Anne-Marie Ruppert1, Vincent Fallet3, Michael Duruisseaux3, Etienne Giroux Leprieur3, Virginie Poulot4, Nathalie Rabbe3, Laurene Sclick3, Michele Beau-Faller5, Roger Lacave6, Armelle Lavole3, Jacques Cadranel1, Marie Wislez7. 1. Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, Service de Pneumologie, F-75970 Paris, France. 2. Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, Service d'Anatomie pathologique, F-75970 Paris, France. 3. Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France. 4. Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, Plateforme de Génomique des Tumeurs Solides, F-75970 Paris, France. 5. Hôpital de Hautepierre, Laboratoire de Biochimie et de biologie moléculaire, F-67098 Strasbourg, France. 6. AP-HP, Hôpital Tenon, Plateforme de Génomique des Tumeurs Solides, F-75970 Paris, France. 7. Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, Service de Pneumologie, F-75970 Paris, France. Electronic address: marie.wislez@tnn.aphp.fr.
Abstract
OBJECTIVES: Pulmonary sarcomatoid carcinomas (SC) are highly disseminated types of non-small-cell lung carcinoma. Their prognosis is poor. New therapeutic targets are needed to improve disease management. MATERIALS AND METHODS: From 1995 to 2013, clinical and survival data from all consecutive patients with surgically treated SC were collected. Pathological and biomarker analyses were performed: TTF1, P63, c-MET and ALK expression (immunohistochemistry), PAS staining, ALK rearrangement (FISH), and EGFR, KRAS, HER2, BRAF, PIK3CA, and MET genes mutations (PCR). RESULTS: Seventy-seven patients were included. Median age was 61 years (53-69). Histological subtypes were pleomorphic carcinoma (78%), carcinosarcoma (12%), and giant-cell and/or spindle-cell carcinoma (10%). Blood vessel invasion (BVI) was present in 90% of cases. Morphology and immunohistochemistry were indicative of an adenocarcinoma, squamous, and adenosquamous origin in 41.5%, 17% and 11.5%, respectively, 30% remained not-otherwise-specified. KRAS, PIK3CA, EGFR, and MET mutations were found in 31%, 8%, 3%, and 3%, respectively. No tumors had HER2 or BRAF mutations, or ALK rearrangement, whereas 34% had a c-MET positive score. Five-year overall survival (OS) was 29% for the whole population. At multivariate analysis, tumor size <50mm (HR=1.96 [1.04-3.73], p=0.011), no lymph-node metastasis (HR=3.25 [1.68-6.31], p<0.0001), no parietal pleural invasion (HR=1.16 [1.06-1.28], p=0.002), no BVI (HR=1.22 [1.06-1.40], p=0.005), and no squamous component (HR=3.17 [1.48-6.79], p=0.01) were associated with longer OS. Biomarkers did not influence OS. CONCLUSION: Dedifferentiation in NSCLC could lead to SC and an epithelial subtype component could influence outcome. BVI was present in almost all SCs and was an independent factor of poor prognosis.
OBJECTIVES:Pulmonary sarcomatoid carcinomas (SC) are highly disseminated types of non-small-cell lung carcinoma. Their prognosis is poor. New therapeutic targets are needed to improve disease management. MATERIALS AND METHODS: From 1995 to 2013, clinical and survival data from all consecutive patients with surgically treated SC were collected. Pathological and biomarker analyses were performed: TTF1, P63, c-MET and ALK expression (immunohistochemistry), PAS staining, ALK rearrangement (FISH), and EGFR, KRAS, HER2, BRAF, PIK3CA, and MET genes mutations (PCR). RESULTS: Seventy-seven patients were included. Median age was 61 years (53-69). Histological subtypes were pleomorphic carcinoma (78%), carcinosarcoma (12%), and giant-cell and/or spindle-cell carcinoma (10%). Blood vessel invasion (BVI) was present in 90% of cases. Morphology and immunohistochemistry were indicative of an adenocarcinoma, squamous, and adenosquamous origin in 41.5%, 17% and 11.5%, respectively, 30% remained not-otherwise-specified. KRAS, PIK3CA, EGFR, and MET mutations were found in 31%, 8%, 3%, and 3%, respectively. No tumors had HER2 or BRAF mutations, or ALK rearrangement, whereas 34% had a c-MET positive score. Five-year overall survival (OS) was 29% for the whole population. At multivariate analysis, tumor size <50mm (HR=1.96 [1.04-3.73], p=0.011), no lymph-node metastasis (HR=3.25 [1.68-6.31], p<0.0001), no parietal pleural invasion (HR=1.16 [1.06-1.28], p=0.002), no BVI (HR=1.22 [1.06-1.40], p=0.005), and no squamous component (HR=3.17 [1.48-6.79], p=0.01) were associated with longer OS. Biomarkers did not influence OS. CONCLUSION: Dedifferentiation in NSCLC could lead to SC and an epithelial subtype component could influence outcome. BVI was present in almost all SCs and was an independent factor of poor prognosis.