Abstract
Abstract Background: To determine the frequency and prognostic impact of ALK-rearrangements in gastric cancer patients who underwent curative surgical resection with extensive (D2) lymph node dissection. Patients and methods: We concurrently analyzed the ALK-rearrangements and HER2 overexpression in whole tumor sections of 455 curatively resected gastric cancers. We performed immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH), and analyzed the relationship between ALK positivity and clinical survival outcome. Results: Of the 455 tumors that were screened, 38 (8.4%) were ALK+ by IHC, which consisted of 1+ (24, 7.5%), 2+ (3, 0.7%), and 3+ (1, 0.2%), but no cases were confirmed by FISH. ALK+ patients were significantly younger (57 vs. 61 years, P=0.02) and showed similar patterns of ALK+ lung adenocarcinoma. ALK+ patients were significantly more likely to have abundant signet ring cells (defined as ≥ 10% of tumor cells). Moreover, as the ALK intensity (measured by IHC) increased, so did the density of signet ring cell in tumors (Ptrend = 0.02). Also, the disease free survival (DFS) and overall survival (OS) of ALK+ patients in stages were shorter than ALK- patients (DFS: 21.2 vs.100.5 months; P = 0.007, OS: 34.3 months vs. median survival time unattainable; P=0.016) Conclusions: ALK+ is an independent negative prognostic factor in surgically resected gastric cancers and is associated with signet ring cell histology. Furthermore ALK+ might be a relevant therapeutic target in gastric cancer patients. Citation Format: Hongjae Jeon, HyeRyun Kim, Sung Hoon Noh, Hyun Cheol Chung, Sun Young Rha. The clinicopathological features and prognostic impact of ALK-positivity in resected gastric or gastro-esophageal cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 566. doi:10.1158/1538-7445.AM2014-566
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