title: Anaplastic lymphoma kinase (ALK) gene alteration in signet ring cell carcinoma of the gastrointestinal tract.
abstract: OBJECTIVE
  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.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Olatunji B
authors.initials: OB
authors.lastname: Alese
authors.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Bassel F
authors.initials: BF
authors.lastname: El-Rayes
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Sica
authors.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Guojing
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Cancer Tissue and Pathology Shared Resource (CTPSR), Winship Cancer Center of Emory University, Atlanta, GA, USA.
authors.forename: Dianne
authors.initials: D
authors.lastname: Alexis
authors.affiliation: Department of Pathology, University of Colorado School of Medicine, Denver, CO, USA.
authors.forename: Francisco G
authors.initials: FG
authors.lastname: La Rosa
authors.affiliation: Department of Pathology, University of Colorado School of Medicine, Denver, CO, USA.
authors.forename: Marileila
authors.initials: M
authors.lastname: Varella-Garcia
authors.affiliation: Department of Statistics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rossi
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Nazim V
authors.initials: NV
authors.lastname: Adsay
authors.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Fadlo R
authors.initials: FR
authors.lastname: Khuri
authors.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365 Clifton Road, NE, Room C3080, Atlanta, GA 30322, USA.
authors.forename: Taofeek K
authors.initials: TK
authors.lastname: Owonikoko
keywords: ALK rearrangement; ALK-EML4 fusion; colon; signet ring cell cancer; stomach