Han Nayoung, Kim Min A, Lee Hye Seung, Kim Woo Ho
Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Pathobiology. 2015;82(6):269-79. doi: 10.1159/000441149. Epub 2015 Oct 31.
We aimed to evaluate the protein and mRNA expression of fibroblast growth factor receptor 2 (FGFR2) by immunohistochemistry (IHC) and mRNA in situ hybridization (ISH), respectively, and to assess the heterogeneity of FGFR2 expression in gastric cancer (GC).
A tissue microarray containing 362 surgically resected GC tissues and 135 matched metastatic lymph nodes was evaluated using FGFR2b IHC and FGFR2 ISH. FGFR2 fluorescence ISH was also performed in 188 cases.
All FGFR2-amplified cases (5 of 188) showed FGFR2b protein and FGFR2 mRNA overexpression (p < 0.001), and FGFR2 amplification was not identified in FGFR2b IHC- and FGFR2 mRNA ISH-negative cases. Kaplan-Meier survival analysis revealed that FGFR2b protein and FGFR2 mRNA overexpression was significantly associated with a poor overall survival (p < 0.001 and p = 0.012, respectively), and multivariate analyses showed that FGFR2 mRNA overexpression was an independent biomarker of a poor overall survival. Intratumoral heterogeneity of FGFR2b protein and FGFR2 mRNA overexpression was observed in 5 of 9 (55.5%) and 18 of 21 (85.7%) cases, respectively. Discordant FGFR2b and FGFR2 expression results between primary and matched metastatic lymph nodes were observed in 5 of 9 (55.5%) and 4 of 14 (28.6%) cases, respectively.
Intratumoral heterogeneity and discordant FGFR2b expression in primary tumors and metastatic lymph nodes are common in GC.
我们旨在分别通过免疫组织化学（IHC）和mRNA原位杂交（ISH）评估成纤维细胞生长因子受体2（FGFR2）的蛋白质和mRNA表达，并评估FGFR2在胃癌（GC）中表达的异质性。
使用FGFR2b IHC和FGFR2 ISH对包含362例手术切除的GC组织和135个匹配的转移淋巴结的组织微阵列进行评估。还对188例病例进行了FGFR2荧光ISH检测。
所有FGFR2扩增病例（188例中的5例）均显示FGFR2b蛋白和FGFR2 mRNA过表达（p < 0.001），在FGFR2b IHC和FGFR2 mRNA ISH阴性病例中未发现FGFR2扩增。Kaplan-Meier生存分析显示，FGFR2b蛋白和FGFR2 mRNA过表达与总体生存率差显著相关（分别为p < 0.001和p = 0.012），多变量分析表明FGFR2 mRNA过表达是总体生存率差的独立生物标志物。分别在9例中的5例（55.5%）和21例中的18例（85.7%）观察到FGFR2b蛋白和FGFR2 mRNA过表达的肿瘤内异质性。分别在9例中的5例（55.5%）和14例中的4例（28.6%）观察到原发性肿瘤与匹配的转移淋巴结之间FGFR2b和FGFR2表达结果不一致。
肿瘤内异质性以及原发性肿瘤和转移淋巴结中FGFR2b表达不一致在GC中很常见。
