Clinicopathological and genetic characteristics of pulmonary large cell carcinoma under 2015 WHO classification: a pilot study

// Renwang Liu 1, 2, * , Jinghao Liu 1, * , Tao Shi 3, * , Xiongfei Li 1 , Dian Ren 1 , Gang Chen 1 , Ying Li 2 , Hongyu Liu 2 , Song Xu 1, 2 and Jun Chen 1, 2 1 Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China 2 Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China 3 Department of Pathology, Tianjin Medical University General Hospital, Tianjin 300052, China * These authors contributed equally to this work Correspondence to: Jun Chen, email: huntercj2004@yahoo.com Song Xu, email: xusong198@hotmail.com Hongyu Liu, email: liuhongyu123@hotmail.com Keywords: large cell carcinoma, gene mutation, TP53, classification Received: July 21, 2017 Accepted: September 21, 2017 Published: October 11, 2017 ABSTRACT Pulmonary large cell carcinoma (LCC) was re-defined under the 2015 WHO classification criteria. However, the clinicopathological features and genetic mutation statuses of Chinese LCC patients based on the new classification have rarely been investigated. Twenty-four Chinese surgically resected LCC patients previously diagnosed under the 2004 WHO criteria were re-classified under the 2015 WHO criteria. Genetic analysis was performed using next-generation sequencing of 46 cancer-related genes. The correlation of clinicopathological and genetic data was further analyzed. Eight patients were re-defined as LCCs, and 16 patients were defined as non-LCCs under the refined criteria. All LCC patients were male, and 7 patients were smokers. No significant differences in age, gender, smoking status, primary site, TNM staging and overall survival were observed between the LCC and non-LCC patients under the refined criteria. Four of the 8 LCC patients presented TP53 mutations, and no somatic mutations were detected in the other 4 LCCs under the refined criteria. For the 16 non-LCCs, not only TP53 and KRAS but also EGFR, KIT, PIK3CA, PTEN, IDH1, APC, ATM and BRAF mutations were also observed. In addition, LCCs without TP53 mutations did not present any gene mutations under the 2004 or 2015 WHO criteria. Importantly, the patients with TP53 mutation exhibited a trend with a worse survival outcome at the time of follow-up. The new WHO diagnosis criteria have superior performance in precise molecular classification for LCC patients.