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

Hong Jae Chon, Hye Ryun Kim, Eunah Shin, Chan Kim, Su Jin Heo, Choong kun Lee, Jin Kyu Park, Sung Hoon Noh, Hyuncheol Chung, SunYoung Rha

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3938-3945
Number of pages8
JournalAnnals of Surgical Oncology
Volume22
Issue number12
DOIs
Publication statusPublished - 2015 Nov 1

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Stomach Neoplasms
Immunohistochemistry
Survival
Disease-Free Survival
Neoplasms
Fluorescence In Situ Hybridization
Histology
Cellular Structures
Adjuvant Chemotherapy
Epidermal Growth Factor Receptor
Lung Neoplasms
Multivariate Analysis
Recurrence
Proteins

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Chon, Hong Jae ; Kim, Hye Ryun ; Shin, Eunah ; Kim, Chan ; Heo, Su Jin ; Lee, Choong kun ; Park, Jin Kyu ; Noh, Sung Hoon ; Chung, Hyuncheol ; Rha, SunYoung. / The Clinicopathologic Features and Prognostic Impact of ALK Positivity in Patients with Resected Gastric Cancer. In: Annals of Surgical Oncology. 2015 ; Vol. 22, No. 12. pp. 3938-3945.
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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.",
author = "Chon, {Hong Jae} and Kim, {Hye Ryun} and Eunah Shin and Chan Kim and Heo, {Su Jin} and Lee, {Choong kun} and Park, {Jin Kyu} and Noh, {Sung Hoon} and Hyuncheol Chung and SunYoung Rha",
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The Clinicopathologic Features and Prognostic Impact of ALK Positivity in Patients with Resected Gastric Cancer. / Chon, Hong Jae; Kim, Hye Ryun; Shin, Eunah; Kim, Chan; Heo, Su Jin; Lee, Choong kun; Park, Jin Kyu; Noh, Sung Hoon; Chung, Hyuncheol; Rha, SunYoung.

In: Annals of Surgical Oncology, Vol. 22, No. 12, 01.11.2015, p. 3938-3945.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The Clinicopathologic Features and Prognostic Impact of ALK Positivity in Patients with Resected Gastric Cancer

AU - Chon, Hong Jae

AU - Kim, Hye Ryun

AU - Shin, Eunah

AU - Kim, Chan

AU - Heo, Su Jin

AU - Lee, Choong kun

AU - Park, Jin Kyu

AU - Noh, Sung Hoon

AU - Chung, Hyuncheol

AU - Rha, SunYoung

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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.

AB - 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.

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U2 - 10.1245/s10434-015-4376-8

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