BACKGROUND: Classification of high-grade neuroendocrine tumours (HGNT) of the lung currently recognises large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung carcinoma (SCLC) as distinct groups. However, a similarity in histology for these two carcinomas and uncertain clinical course have led to suggestions that a single HGNT classification would be more appropriate. Gene expression profiling, which can reproduce histopathological classification, and often defines new subclasses with prognostic significance, can be used to resolve HGNT classification. METHODS: We used cDNA microarrays with 40?386 elements to analyse the gene expression profiles of 38 surgically resected samples of lung neuroendocrine tumours and 11 SCLC cell lines. Samples of large-cell carcinoma, adenocarcinoma, and normal lung were also included to give a total of 105 samples analysed. The data were subjected to filtering to yield informative genes before unsupervised hierarchical clustering that identified relatedness of tumour samples. FINDINGS: Distinct groups for carcinoids, large-cell carcinoma, adenocarcinoma, and normal lung were readily identified. However, we were unable to distinguish LCNEC from SCLC by gene expression profiling. Three independent rounds of unsupervised hierarchical clustering consistently divided SCLC samples into two main groups with LCNEC samples largely integrated with these groups. Furthermore, patients in one of the groups identified by clustering had a significantly better clinical outcome than the other (83% vs 12% survived for 5 years; p=0.0094. None of the highly proliferative SCLC cell lines subsequently analysed clustered with this good-prognosis group. INTERPRETATION: Our findings show that HGNT of the lung can be classified into two groups independent of SCLC and LCNEC. To this end, we have identified many genes, some of which encode well-characterised markers of cancer that distinguish the HGNT groups. These results have implications for the diagnosis, classification, and treatment of lung neuroendocrine tumours, and provide important insights into their underlying biology.
BACKGROUND: Classification of high-grade neuroendocrine tumours (HGNT) of the lung currently recognises large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung carcinoma (SCLC) as distinct groups. However, a similarity in histology for these two carcinomas and uncertain clinical course have led to suggestions that a single HGNT classification would be more appropriate. Gene expression profiling, which can reproduce histopathological classification, and often defines new subclasses with prognostic significance, can be used to resolve HGNT classification. METHODS: We used cDNA microarrays with 40?386 elements to analyse the gene expression profiles of 38 surgically resected samples of lung neuroendocrine tumours and 11 SCLC cell lines. Samples of large-cell carcinoma, adenocarcinoma, and normal lung were also included to give a total of 105 samples analysed. The data were subjected to filtering to yield informative genes before unsupervised hierarchical clustering that identified relatedness of tumour samples. FINDINGS: Distinct groups for carcinoids, large-cell carcinoma, adenocarcinoma, and normal lung were readily identified. However, we were unable to distinguish LCNEC from SCLC by gene expression profiling. Three independent rounds of unsupervised hierarchical clustering consistently divided SCLC samples into two main groups with LCNEC samples largely integrated with these groups. Furthermore, patients in one of the groups identified by clustering had a significantly better clinical outcome than the other (83% vs 12% survived for 5 years; p=0.0094. None of the highly proliferative SCLC cell lines subsequently analysed clustered with this good-prognosis group. INTERPRETATION: Our findings show that HGNT of the lung can be classified into two groups independent of SCLC and LCNEC. To this end, we have identified many genes, some of which encode well-characterised markers of cancer that distinguish the HGNT groups. These results have implications for the diagnosis, classification, and treatment of lung neuroendocrine tumours, and provide important insights into their underlying biology.
Authors: Nadia A Atai; Manju Bansal; Cheungh Lo; Joost Bosman; Wikky Tigchelaar; Klazien S Bosch; Ard Jonker; Philip C De Witt Hamer; Dirk Troost; Christopher A McCulloch; Vincent Everts; Cornelis J F Van Noorden; Jaro Sodek Journal: Immunology Date: 2010-08-17 Impact factor: 7.397
Authors: Paul A Bunn; John D Minna; Alexander Augustyn; Adi F Gazdar; Youcef Ouadah; Mark A Krasnow; Anton Berns; Elisabeth Brambilla; Natasha Rekhtman; Pierre P Massion; Matthew Niederst; Martin Peifer; Jun Yokota; Ramaswamy Govindan; John T Poirier; Lauren A Byers; Murry W Wynes; David G McFadden; David MacPherson; Christine L Hann; Anna F Farago; Caroline Dive; Beverly A Teicher; Craig D Peacock; Jane E Johnson; Melanie H Cobb; Hans-Guido Wendel; David Spigel; Julien Sage; Ping Yang; M Catherine Pietanza; Lee M Krug; John Heymach; Peter Ujhazy; Caicun Zhou; Koichi Goto; Afshin Dowlati; Camilla Laulund Christensen; Keunchil Park; Lawrence H Einhorn; Martin J Edelman; Giuseppe Giaccone; David E Gerber; Ravi Salgia; Taofeek Owonikoko; Shakun Malik; Niki Karachaliou; David R Gandara; Ben J Slotman; Fiona Blackhall; Glenwood Goss; Roman Thomas; Charles M Rudin; Fred R Hirsch Journal: J Thorac Oncol Date: 2016-01-30 Impact factor: 15.609
Authors: Giuseppe Pelosi; Aldo Scarpa; Giulia Veronesi; Lorenzo Spaggiari; Barbara Del Curto; Patrick S Moore; Patrick Maisonneuve; Angelica Sonzogni; Michele Masullo; Giuseppe Viale Journal: Virchows Arch Date: 2005-09-13 Impact factor: 4.064
Authors: Pablo Tamayo; Daniel Scanfeld; Benjamin L Ebert; Michael A Gillette; Charles W M Roberts; Jill P Mesirov Journal: Proc Natl Acad Sci U S A Date: 2007-03-27 Impact factor: 11.205
Authors: Alexander Augustyn; Mark Borromeo; Tao Wang; Junya Fujimoto; Chunli Shao; Patrick D Dospoy; Victoria Lee; Christopher Tan; James P Sullivan; Jill E Larsen; Luc Girard; Carmen Behrens; Ignacio I Wistuba; Yang Xie; Melanie H Cobb; Adi F Gazdar; Jane E Johnson; John D Minna Journal: Proc Natl Acad Sci U S A Date: 2014-09-29 Impact factor: 11.205