Hong Jae Chon1,2, Hye Ryun Kim1,2, Eunah Shin3, Chan Kim1,2, Su Jin Heo1, Choong-Kun Lee1, Jin Kyu Park3, Sung Hoon Noh4, Hyun Cheol Chung1,2,5, Sun Young Rha6,7,8. 1. Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea. 2. Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea. 3. CFC Pathology Laboratory, Seoul, Korea. 4. Department of Surgery, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea. 5. Cancer Metastasis Research Center, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea. 6. Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea. rha7655@yuhs.ac. 7. Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea. rha7655@yuhs.ac. 8. Cancer Metastasis Research Center, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea. rha7655@yuhs.ac.
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.
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 cancerpatients 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: 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