title: Malignant pleural effusion cell blocks are substitutes for tissue in EML4-ALK rearrangement detection in patients with advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  To evaluate the feasibility of malignant pleural effusions (MPE) as surrogate samples for the detection of echinoderm microtubule-associated protein-like4 (EML4)-anaplastic lymphoma kinase (ALK) and to investigate the prognostic and predictive value of EML4-ALK in MPE of non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  One hundred and nine NSCLC patients were retrospectively analysed. EML4-ALK was identified using paraffin-embedded tumour cells in MPE samples by immunohistochemistry (IHC, Ventana) and confirmed by fluorescence using in situ hybridisation (FISH) and qRT-PCR. The EGFR mutation was determined by MPE, using denaturing high-performance liquid chromatography (DHPLC).
  
  
  RESULTS
  A total of 5 out of 109 (4.58%) patients were identified as EML4-ALK rearrangement in MPE by IHC.; In addition to two metachronous samples, the consistency of MPE and tissue for EML4-ALK detection was 100% (21/21), and the sensitivity and specificity were 100% (2/2) and 100% (19/19), respectively. EML4-ALK rearrangement cases were confirmed by FISH and qRT-PCR; the sensitivity were both 100% (2/2) when compared with tissue, and it was 60% (3/5) and 100% (5/5), respectively, when compared with MPE by IHC. The overall response rate (ORR) was 100% (2/2) for patients with EML4-ALK in MPE. Moreover, the PFS of these patients appeared to be prolonged in chemotherapy (9.27 versus 6.53 and versus 4.67 months, P = 0.122), compared with the EGFR mutation and the EGFR/ALK double negative group, respectively.
  
  
  CONCLUSIONS
  EML4-ALK rearrangement detection in malignant pleural effusions is a complementary method for EML4-ALK detection. VETANA and qRT-PCR are more appropriate for MPE detection. EML4-ALK rearrangement in pleural effusions has a predictive value for treatment.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology I, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology I, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Bai
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology I, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology I, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology I, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Duan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology I, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: T
authors.initials: T
authors.lastname: An
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology I, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: M
authors.initials: M
authors.lastname: Wu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology I, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology I, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology I, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D003581:Cytodiagnosis; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000302:isolation & purification; D016066:Pleural Effusion, Malignant / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011379:Prognosis
chemical_list: C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EML4-ALK fusion protein; epidermal growth factor receptor; immunohistochemistry; lung cancer; pleural effusion