Filippo Lococo1, Greta Gandolfi2, Giulio Rossi3, Carmine Pinto4, Cristian Rapicetta5, Alberto Cavazza6, Alfredo Cesario7, Carla Galeone5, Massimiliano Paci5, Alessia Ciarrocchi2. 1. Unit of Thoracic Surgery, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy. Electronic address: filippo_lococo@yahoo.it. 2. Laboratory of Translational Research, Research and Statistic Infrastructure, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy. 3. Unit of Pathology, University of Modena and Reggio Emilia, Modena, Italy. 4. Department of Oncology and Advanced Technologies, Operative Unit of Oncology, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy. 5. Unit of Thoracic Surgery, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy. 6. Unit of Pathology, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy. 7. Office for International Research Activities and Systems Medicine, Scientific Direction, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
Abstract
INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subset of non-small cell lung cancer with limited treatment options. The molecular characterization of PSC has been strongly hampered by the relative rarity of these tumors. However, understanding the molecular and genetic bases of PSCs is critical to pave the way to new treatment options. In this work, we aimed to explore the complexity of the genetic asset of PSC and investigate its prognostic impact on survival in a large cohort of patients with PSC. METHODS: Next-generation sequencing analysis of a panel of 26 genes with potential clinical relevance was performed on surgical specimens of 49 PSCs. The prognostic impact of genetic profiles on patient survival and the association between the genetic alterations and clinicopathological features were tested. RESULTS: Fifty-five somatic mutations were detected in 13 genes. Thirty-nine PSCs (80%) showed at least one mutation. Survival probability decreased in patients with mutated PSC compared with in those with PSC without mutations (p = 0.02). In particular, mutations in Kirsten rat sarcoma viral oncogene homolog gene (KRAS), alone or in combination with tumor protein p53 gene (TP53) mutations, were associated with decreased survival probability and with the occurrence of local metastases at recurrence. Finally, comparison of our results with data in The Cancer Genome Atlas showed that PSCs have a mutational profile similar to that of smokers' lung adenocarcinoma. CONCLUSIONS: Overall, our analysis provides further information on the mutational profiles of PSCs and demonstrates for the first time a role of KRAS mutations in driving the aggressiveness of this type of cancer.
INTRODUCTION:Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subset of non-small cell lung cancer with limited treatment options. The molecular characterization of PSC has been strongly hampered by the relative rarity of these tumors. However, understanding the molecular and genetic bases of PSCs is critical to pave the way to new treatment options. In this work, we aimed to explore the complexity of the genetic asset of PSC and investigate its prognostic impact on survival in a large cohort of patients with PSC. METHODS: Next-generation sequencing analysis of a panel of 26 genes with potential clinical relevance was performed on surgical specimens of 49 PSCs. The prognostic impact of genetic profiles on patient survival and the association between the genetic alterations and clinicopathological features were tested. RESULTS: Fifty-five somatic mutations were detected in 13 genes. Thirty-nine PSCs (80%) showed at least one mutation. Survival probability decreased in patients with mutated PSC compared with in those with PSC without mutations (p = 0.02). In particular, mutations in Kirsten ratsarcoma viral oncogene homolog gene (KRAS), alone or in combination with tumor protein p53 gene (TP53) mutations, were associated with decreased survival probability and with the occurrence of local metastases at recurrence. Finally, comparison of our results with data in The Cancer Genome Atlas showed that PSCs have a mutational profile similar to that of smokers' lung adenocarcinoma. CONCLUSIONS: Overall, our analysis provides further information on the mutational profiles of PSCs and demonstrates for the first time a role of KRAS mutations in driving the aggressiveness of this type of cancer.