title: Pulmonary Sarcomatoid Carcinoma with ALK Rearrangement: Frequency, Clinical-Pathologic Characteristics, and Response to ALK Inhibitor.
abstract: OBJECTIVE
  The incidence of anaplastic lymphoma kinase (ALK) rearrangement in pulmonary sarcomatoid carcinoma (PSC) is controversial. In this study, we aimed to reveal the reliable frequency and the clinical-pathologic characteristics of pulmonary sarcomatoid carcinoma (PSC) with ALK rearrangement in Chinese population, and to provide insight into the translatability of anti-ALK treatment in this treatment-refractory disease.
  
  
  METHODS
  Immunohistochemistry (IHC) using a Ventana anti-ALK (D5F3) rabbit monoclonal antibody was performed in 141 PSC specimens collected from multiple medical centers. IHC-positive cases were then confirmed using ALK fluorescent in situ hybridization (FISH). The incidence rates and clinical-pathologic characteristics of ALK-rearranged PSC were then analyzed. Response to ALK inhibitor crizotinib in a patient with ALK-rearranged PSC was evaluated according to the response evaluation criteria for solid tumors (RECIST) version 1.1.
  
  
  RESULTS
  Five of 141 (3.5%) of PSCs showed ALK rearrangement-positive by IHC and then were confirmed by FISH. Two were carcinosarcomas and the other three were pulmonary pleomorphic carcinoma (PPC). Strong positive ALK rearrangement was observed in both the epithelioid and sarcomatoid components. The median age of ALK-positive patients was younger than that of ALK-negative patients. PSCs in never-smokers were more likely to harbor ALK rearrangement than those in former or current smokers (P<.05). A 40-year-old woman diagnosed with ALK-rearranged PPC experienced a partial response (-32%) to the ALK inhibitor crizotinib.
  
  
  CONCLUSIONS
  The incidence rates of ALK rearrangement in PSC in the Chinese population are similar to those of other subtypes of NSCLC. PSCs in younger never-smokers are more often to harbor ALK rearrangement. ALK inhibitors may serve as an effective treatment for ALK-rearranged PSC.
authors.affiliation: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, PR China; State Key Laboratory of Oncology in South, China; Collaborative Innovation Center for Cancer Medicine.
authors.forename: Xinru
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South, China; Collaborative Innovation Center for Cancer Medicine; Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South, China; Collaborative Innovation Center for Cancer Medicine; Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, PR China.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Pathology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, PR China.
authors.forename: Chunwei
authors.initials: C
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oncology in South, China; Collaborative Innovation Center for Cancer Medicine; Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, PR China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Oncology in South, China; Collaborative Innovation Center for Cancer Medicine; Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, PR China.
authors.forename: Wenyong
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Pathology, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, PR China.
authors.forename: Sangao
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, PR China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Respiratory Medicine, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, PR China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, PR China; Key Laboratory of Translational Radiation Oncology, Hunan Province.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, PR China; Key Laboratory of Translational Radiation Oncology, Hunan Province. Electronic address: avein_liu@hotmail.com.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, PR China; State Key Laboratory of Oncology in South, China; Collaborative Innovation Center for Cancer Medicine. Electronic address: chenlk@sysucc.org.cn.
authors.forename: Likun
authors.initials: L
authors.lastname: Chen