title: The Clinicopathologic Features and Prognostic Impact of ALK Positivity in Patients with Resected Gastric Cancer.
abstract: BACKGROUND
  Rearrangement of ALK is an established driver aberration in lung cancer. Accordingly, this study attempted to determine the frequency and prognostic impact of ALK alterations in patients with surgically resected gastric cancer.
  
  
  METHODS
  The study evaluated ALK alterations in whole tumor sections of 455 curatively resected gastric cancers via immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). Any expression of ALK protein (1+, 2+, 3+ by IHC) was considered as evidence of ALK positivity (ALK+), and the relationship between ALK positivity and clinicopathologic parameters, including survival outcome, was analyzed.
  
  
  RESULTS
  Of the 455 tumors, 38 (8.4 %) were ALK positive, as measured by IHC. Among the ALK+ patients, two displayed break-apart signals of 5 and 11 % on FISH, respectively. The ALK+ patients were younger (57 vs. 61 years; P = 0.02) and more likely to exhibit a signet ring cell component. Moreover, as ALK intensity measured by IHC increased, so did the proportion of signet ring cells in tumors (defined as ≥10 % of tumor cells; P = 0.02). In terms of survival outcome, the ALK+ patients displayed worse disease-free survival (DFS) and overall survival (OS) than the ALK- patients (P = 0.010 for DFS; P = 0.023 for OS). Multivariate analysis demonstrated that ALK+ gastric cancer patients were at an increased risk of recurrence and death after adjustment for sex, age, tumor location, stage, adjuvant chemotherapy, histology, and epidermal growth factor receptor 2 (HER2) positivity (P = 0.04 for DFS; P = 0.02 for OS).
  
  
  CONCLUSIONS
  The findings showed ALK positivity to be an independent negative prognostic factor in surgically resected gastric cancers associated with signet ring cell histology.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.|Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.
authors.forename: Hong Jae
authors.initials: HJ
authors.lastname: Chon
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.|Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.
authors.forename: Hye Ryun
authors.initials: HR
authors.lastname: Kim
authors.affiliation: CFC Pathology Laboratory, Seoul, Korea.
authors.forename: Eunah
authors.initials: E
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.|Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.
authors.forename: Chan
authors.initials: C
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Heo
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.
authors.forename: Choong-Kun
authors.initials: CK
authors.lastname: Lee
authors.affiliation: CFC Pathology Laboratory, Seoul, Korea.
authors.forename: Jin Kyu
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Noh
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.|Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.|Cancer Metastasis Research Center, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea. rha7655@yuhs.ac.|Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea. rha7655@yuhs.ac.|Cancer Metastasis Research Center, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea. rha7655@yuhs.ac.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D018572:Disease-Free Survival; D004943:Esophagogastric Junction; D005260:Female; D005743:Gastrectomy; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D013274:Stomach Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C000626173:ALK protein, human; C508053:ERBB2 protein, human