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The Clinicopathologic Features and Prognostic Impact of ALK Positivity in Patients with Resected Gastric Cancer

Authors
 Hong Jae Chon  ;  Hye Ryun Kim  ;  Eunah Shin  ;  Chan Kim  ;  Su Jin Heo  ;  Choong-kun Lee  ;  Jin Kyu Park  ;  Sung Hoon Noh  ;  Hyun Cheol Chung  ;  Sun Young Rha 
Citation
 Annals of Surgical Oncology, Vol.22(12) : 3938-3945, 2015 
Journal Title
 Annals of Surgical Oncology 
ISSN
 1068-9265 
Issue Date
2015
MeSH
Adenocarcinoma/chemistry ; Adenocarcinoma/genetics* ; Adenocarcinoma/pathology* ; Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Disease-Free Survival ; Esophagogastric Junction* ; Female ; Gastrectomy ; Gene Rearrangement ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Receptor Protein-Tyrosine Kinases/analysis ; Receptor Protein-Tyrosine Kinases/genetics* ; Receptor, ErbB-2/analysis ; Stomach Neoplasms/chemistry ; Stomach Neoplasms/genetics* ; Stomach Neoplasms/pathology* ; Survival Rate ; Young Adult
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.
Full Text
https://link.springer.com/article/10.1245/s10434-015-4376-8
DOI
10.1245/s10434-015-4376-8
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Noh, Sung Hoon(노성훈) ORCID logo https://orcid.org/0000-0003-4386-6886
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Chon, Hong Jae(전홍재)
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Heo, Su Jin(허수진) ORCID logo https://orcid.org/0000-0002-0615-5869
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/156970
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