Chon Hong Jae, Kim Hye Ryun, Shin Eunah, Kim Chan, Heo Su Jin, Lee Choong-Kun, Park Jin Kyu, Noh Sung Hoon, Chung Hyun Cheol, Rha Sun Young
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.
Ann Surg Oncol. 2015 Nov;22(12):3938-45. doi: 10.1245/s10434-015-4376-8. Epub 2015 Feb 24.
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.
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.
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).
The findings showed ALK positivity to be an independent negative prognostic factor in surgically resected gastric cancers associated with signet ring cell histology.
ALK重排是肺癌中已确定的驱动性畸变。因此，本研究试图确定手术切除的胃癌患者中ALK改变的频率及其对预后的影响。
本研究通过免疫组织化学（IHC）和荧光原位杂交（FISH）评估了455例根治性切除的胃癌全肿瘤切片中的ALK改变。ALK蛋白的任何表达（IHC显示为1+、2+、3+）均被视为ALK阳性（ALK+）的证据，并分析了ALK阳性与包括生存结果在内的临床病理参数之间的关系。
在455例肿瘤中，通过IHC检测，38例（8.4%）为ALK阳性。在ALK+患者中，两名患者在FISH上分别显示5%和11%的分离信号。ALK+患者更年轻（57岁对61岁；P = 0.02），且更有可能表现出印戒细胞成分。此外，随着通过IHC测量的ALK强度增加，肿瘤中印戒细胞的比例也增加（定义为≥肿瘤细胞的10%；P = 0.02）。在生存结果方面，ALK+患者的无病生存期（DFS）和总生存期（OS）均比ALK-患者差（DFS的P = 0.010；OS的P = 0.023）。多变量分析表明，在对性别、年龄、肿瘤位置、分期、辅助化疗、组织学和表皮生长因子受体2（HER2）阳性进行校正后，ALK+胃癌患者复发和死亡的风险增加（DFS的P = 0.04；OS的P = 0.02）。
研究结果表明，ALK阳性是手术切除的、与印戒细胞组织学相关的胃癌的独立负性预后因素。
