BACKGROUND: The origins of and interrelations between low grade and high grade neuroendocrine lung tumors, typical and atypical carcinoids, and small cell lung carcinoma (SCLC) have not been elucidated. Karyotypic and molecular genetic studies have demonstrated deletions in 3p in 100% of SCLCs and the candidate lung tumor suppressor gene, FHIT, at 3p14.2 is not expressed in the majority of SCLCs. Similar studies of typical and atypical carcinoids could clarify the interrelations among these tumors. METHODS: For molecular genetic analyses, archival carcinoids and paired normal cells were microdissected from paraffin sections, deparaffinized, and DNA prepared. Oligonucleotide primer pairs for 12 microsatellite markers mapping between 3p14.2 and 3p21.3 were used to amplify allelic DNA fragments from 13 typical and 6 atypical carcinoids. In addition, an independent series of archival sections of carcinoids and SCLCs was tested by immunohistochemistry for expression of Fhit protein. RESULTS: Of the six atypical carcinoids examined, three had lost an allele at all informative markers, whereas one had lost alleles in two distinct regions and two showed allele loss in a subregion of the chromosome region tested. Of the 13 typical carcinoids, 3 showed allele loss at only 1 or 2 loci each. Typical carcinoids, similar to normal lung epithelia, were strongly positive for the cytoplasmic Fhit protein, SCLCs were uniformly negative, and atypical carcinoids appeared to express an intermediate level of Fhit protein. CONCLUSIONS: Loss of heterozygosity at 3p14.2-p21.3 is significantly more extensive in all atypical carcinoids. Atypical carcinoids, which exhibit clinicopathologic features intermediate between typical carcinoids and small cell carcinomas and have been considered well differentiated neuroendocrine carcinomas, also are intermediate between typical carcinoids and SCLC on the basis of extent of loss of 3p alleles and reduced expression of Fhit protein.
BACKGROUND: The origins of and interrelations between low grade and high grade neuroendocrine lung tumors, typical and atypical carcinoids, and small cell lung carcinoma (SCLC) have not been elucidated. Karyotypic and molecular genetic studies have demonstrated deletions in 3p in 100% of SCLCs and the candidate lung tumor suppressor gene, FHIT, at 3p14.2 is not expressed in the majority of SCLCs. Similar studies of typical and atypical carcinoids could clarify the interrelations among these tumors. METHODS: For molecular genetic analyses, archival carcinoids and paired normal cells were microdissected from paraffin sections, deparaffinized, and DNA prepared. Oligonucleotide primer pairs for 12 microsatellite markers mapping between 3p14.2 and 3p21.3 were used to amplify allelic DNA fragments from 13 typical and 6 atypical carcinoids. In addition, an independent series of archival sections of carcinoids and SCLCs was tested by immunohistochemistry for expression of Fhit protein. RESULTS: Of the six atypical carcinoids examined, three had lost an allele at all informative markers, whereas one had lost alleles in two distinct regions and two showed allele loss in a subregion of the chromosome region tested. Of the 13 typical carcinoids, 3 showed allele loss at only 1 or 2 loci each. Typical carcinoids, similar to normal lung epithelia, were strongly positive for the cytoplasmic Fhit protein, SCLCs were uniformly negative, and atypical carcinoids appeared to express an intermediate level of Fhit protein. CONCLUSIONS: Loss of heterozygosity at 3p14.2-p21.3 is significantly more extensive in all atypical carcinoids. Atypical carcinoids, which exhibit clinicopathologic features intermediate between typical carcinoids and small cell carcinomas and have been considered well differentiated neuroendocrine carcinomas, also are intermediate between typical carcinoids and SCLC on the basis of extent of loss of 3p alleles and reduced expression of Fhit protein.
Authors: Joshua Smith; Aditi Kulkarni; Andrew C Birkeland; Jonathan B McHugh; J Chad Brenner Journal: Otolaryngol Head Neck Surg Date: 2018-05-08 Impact factor: 3.497
Authors: Julie George; Jing Shan Lim; Se Jin Jang; Yupeng Cun; Luka Ozretić; Gu Kong; Frauke Leenders; Xin Lu; Lynnette Fernández-Cuesta; Graziella Bosco; Christian Müller; Ilona Dahmen; Nadine S Jahchan; Kwon-Sik Park; Dian Yang; Anthony N Karnezis; Dedeepya Vaka; Angela Torres; Maia Segura Wang; Jan O Korbel; Roopika Menon; Sung-Min Chun; Deokhoon Kim; Matt Wilkerson; Neil Hayes; David Engelmann; Brigitte Pützer; Marc Bos; Sebastian Michels; Ignacija Vlasic; Danila Seidel; Berit Pinther; Philipp Schaub; Christian Becker; Janine Altmüller; Jun Yokota; Takashi Kohno; Reika Iwakawa; Koji Tsuta; Masayuki Noguchi; Thomas Muley; Hans Hoffmann; Philipp A Schnabel; Iver Petersen; Yuan Chen; Alex Soltermann; Verena Tischler; Chang-min Choi; Yong-Hee Kim; Pierre P Massion; Yong Zou; Dragana Jovanovic; Milica Kontic; Gavin M Wright; Prudence A Russell; Benjamin Solomon; Ina Koch; Michael Lindner; Lucia A Muscarella; Annamaria la Torre; John K Field; Marko Jakopovic; Jelena Knezevic; Esmeralda Castaños-Vélez; Luca Roz; Ugo Pastorino; Odd-Terje Brustugun; Marius Lund-Iversen; Erik Thunnissen; Jens Köhler; Martin Schuler; Johan Botling; Martin Sandelin; Montserrat Sanchez-Cespedes; Helga B Salvesen; Viktor Achter; Ulrich Lang; Magdalena Bogus; Peter M Schneider; Thomas Zander; Sascha Ansén; Michael Hallek; Jürgen Wolf; Martin Vingron; Yasushi Yatabe; William D Travis; Peter Nürnberg; Christian Reinhardt; Sven Perner; Lukas Heukamp; Reinhard Büttner; Stefan A Haas; Elisabeth Brambilla; Martin Peifer; Julien Sage; Roman K Thomas Journal: Nature Date: 2015-07-13 Impact factor: 49.962
Authors: Giulia Veronesi; David R Baldwin; Claudia I Henschke; Simone Ghislandi; Sergio Iavicoli; Matthijs Oudkerk; Harry J De Koning; Joseph Shemesh; John K Field; Javier J Zulueta; Denis Horgan; Lucia Fiestas Navarrete; Maurizio Valentino Infante; Pierluigi Novellis; Rachael L Murray; Nir Peled; Cristiano Rampinelli; Gaetano Rocco; Witold Rzyman; Giorgio Vittorio Scagliotti; Martin C Tammemagi; Luca Bertolaccini; Natthaya Triphuridet; Rowena Yip; Alexia Rossi; Suresh Senan; Giuseppe Ferrante; Kate Brain; Carlijn van der Aalst; Lorenzo Bonomo; Dario Consonni; Jan P Van Meerbeeck; Patrick Maisonneuve; Silvia Novello; Anand Devaraj; Zaigham Saghir; Giuseppe Pelosi Journal: Cancers (Basel) Date: 2020-06-24 Impact factor: 6.639