Olatunji B Alese1, Bassel F El-Rayes1, Gabriel Sica2, Guojing Zhang1, Dianne Alexis3, Francisco G La Rosa4, Marileila Varella-Garcia4, Zhengjia Chen5, Michael R Rossi6, Nazim V Adsay2, Fadlo R Khuri1, Taofeek K Owonikoko7. 1. Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA. 2. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. 3. Cancer Tissue and Pathology Shared Resource (CTPSR), Winship Cancer Center of Emory University, Atlanta, GA, USA. 4. Department of Pathology, University of Colorado School of Medicine, Denver, CO, USA. 5. Department of Statistics, Rollins School of Public Health, Emory University, Atlanta, GA, USA. 6. Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, USA. 7. Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365 Clifton Road, NE, Room C3080, Atlanta, GA 30322, USA.
Abstract
OBJECTIVES: ALK-EML4 translocation is an established driver aberration in non-small cell lung cancer (NSCLC), with reported predilection for cases with signet ring histology. We assessed the presence of anaplastic lymphoma kinase (ALK) gene rearrangements in signet ring cancers arising in the stomach and colon. METHODS: Histologically confirmed cases of signet ring adenocarcinoma of the stomach or the colon were identified. The presence of the classic ALK and EML4 fusion gene was initially determined by fluorescence in-situ hybridization (FISH) technique. Immunohistochemistry (IHC) was performed using two previously validated antibodies, ALK1 clone (1:100; DAKO) and 5A4 (Novocastra, Leica Biosystems) along with positive controls of ALK-translocated lung cancer. RESULTS: We employed 42 cases of signet ring carcinoma diagnosed between 2001 and 2011; 25 gastric and 17 colon cancer. Median age 63.3 years; male/female 17/25; race, black 47.5%, white 47.5%, others, 5%; stage I, 21.4%; stage II, 31%; stage III, 26.2%; stage IV, 21.4%. One of 42 cases (2.3%) was positive for ALK translocation by FISH using the standard criteria of at least 15% positive cells for the break-apart signal (50-70 cells enumerated per case). Using a less restrictive cut-off of 10% positive cells, 7 cases (16%) were considered possibly positive. None of the 'possibly positive' cases was found to harbor ALK translocation by another molecular testing approach (IHC). IHC with two previously validated monoclonal antibodies showed 0 of 42 (0%) cases positive. CONCLUSIONS: ALK gene rearrangement is very rare in gastrointestinal cancers and enrichment strategy focusing on signet ring cell histology did not significantly improve the detection rate.
OBJECTIVES: ALK-EML4 translocation is an established driver aberration in non-small cell lung cancer (NSCLC), with reported predilection for cases with signet ring histology. We assessed the presence of anaplastic lymphoma kinase (ALK) gene rearrangements in signet ring cancers arising in the stomach and colon. METHODS: Histologically confirmed cases of signet ring adenocarcinoma of the stomach or the colon were identified. The presence of the classic ALK and EML4 fusion gene was initially determined by fluorescence in-situ hybridization (FISH) technique. Immunohistochemistry (IHC) was performed using two previously validated antibodies, ALK1 clone (1:100; DAKO) and 5A4 (Novocastra, Leica Biosystems) along with positive controls of ALK-translocated lung cancer. RESULTS: We employed 42 cases of signet ring carcinoma diagnosed between 2001 and 2011; 25 gastric and 17 colon cancer. Median age 63.3 years; male/female 17/25; race, black 47.5%, white 47.5%, others, 5%; stage I, 21.4%; stage II, 31%; stage III, 26.2%; stage IV, 21.4%. One of 42 cases (2.3%) was positive for ALK translocation by FISH using the standard criteria of at least 15% positive cells for the break-apart signal (50-70 cells enumerated per case). Using a less restrictive cut-off of 10% positive cells, 7 cases (16%) were considered possibly positive. None of the 'possibly positive' cases was found to harbor ALK translocation by another molecular testing approach (IHC). IHC with two previously validated monoclonal antibodies showed 0 of 42 (0%) cases positive. CONCLUSIONS: ALK gene rearrangement is very rare in gastrointestinal cancers and enrichment strategy focusing on signet ring cell histology did not significantly improve the detection rate.
Authors: John W Park; Robert S Kerbel; Gary J Kelloff; J Carl Barrett; Bruce A Chabner; David R Parkinson; Jonathan Peck; Raymond W Ruddon; Caroline C Sigman; Dennis J Slamon Journal: Clin Cancer Res Date: 2004-06-01 Impact factor: 12.531
Authors: D Ross Camidge; Mariana Theodoro; Delee A Maxson; Margaret Skokan; Tara O'Brien; Xian Lu; Robert C Doebele; Anna E Barón; Marileila Varella-Garcia Journal: Cancer Date: 2012-01-26 Impact factor: 6.860
Authors: Mari Mino-Kenudson; Lucian R Chirieac; Kenny Law; Jason L Hornick; Neal Lindeman; Eugene J Mark; David W Cohen; Bruce E Johnson; Pasi A Jänne; A John Iafrate; Scott J Rodig Journal: Clin Cancer Res Date: 2010-02-23 Impact factor: 12.531
Authors: Sanjay Popat; David Gonzalez; Toon Min; John Swansbury; Melissa Dainton; James G Croud; Alexandra J Rice; Andrew G Nicholson Journal: Lung Cancer Date: 2011-08-19 Impact factor: 5.705
Authors: P Bavi; Z Jehan; R Bu; S Prabhakaran; N Al-Sanea; F Al-Dayel; M Al-Assiri; T Al-Halouly; R Sairafi; S Uddin; K S Al-Kuraya Journal: Br J Cancer Date: 2013-10-15 Impact factor: 7.640
Authors: Margherita Ambrosini; Marzia Del Re; Paolo Manca; Andrew Hendifar; Alexander Drilon; Guilherme Harada; Anne Hansen Ree; Samuel Klempner; Gunhild Mari Mælandsmo; Kjersti Flatmark; Hege G Russnes; James M Cleary; Harshabad Singh; Elisa Sottotetti; Antonia Martinetti; Giovanni Randon; Andrea Sartore-Bianchi; Iolanda Capone; Massimo Milione; Maria Di Bartolomeo; Filippo Pietrantonio Journal: JCO Precis Oncol Date: 2022-04
Authors: Thomas A Peterson; Iris Ivy M Gauran; Junyong Park; DoHwan Park; Maricel G Kann Journal: PLoS Comput Biol Date: 2017-04-20 Impact factor: 4.475