FGFR2 Assessment in Gastric Cancer Using Quantitative Real-Time Polymerase Chain Reaction, Fluorescent In Situ Hybridization, and Immunohistochemistry.

用实时定量聚合酶链反应（RT-qPCR）、荧光原位杂交（FISH）和免疫组化（IHC）方法检测胃癌中的FGFR2

Park YS,Na YS,Ryu MH,Lee CW,Park HJ,Lee JK,Park SR,Ryoo BY,Kang YK

阅读：507 American Journal of Clinical Pathology； June; 143 (6) : 766 - 911:865-72

Abstract

Fibroblast growth factor receptor 2 (FGFR2) amplification has been reported to be a target for treatment in gastric cancer. However, an optimal tissue source and method for evaluating FGFR2 have yet to be established.
Copy numbers were compared by quantitative polymerase chain reaction (qPCR) using frozen vs formalin-fixed, paraffin-embedded (FFPE) tissue and biopsy vs surgical specimens. We correlated the results of qPCR and immunohistochemistry (IHC) with fluorescence in situ hybridization (FISH) using stage IV gastric cancer biopsy specimens and validated the results in surgical specimens.
FFPE tissues were suitable for qPCR, and biopsy specimens were equivalent to or better than surgical specimens. qPCR and IHC results exhibited an excellent correlation with FISH at eight or more copies by qPCR in any kind of tissue, 5% or more by IHC in biopsy specimens, and 10% or more by IHC in surgical specimens. FGFR2 amplification was 6.6% in stage IV gastric cancers, and 42% of these showed heterogeneous amplification and overexpression. IHC indicated a good correlation with FISH even in the heterogeneous cases.
FFPE biopsy tissues are an adequate source for FGFR2 evaluation in gastric carcinomas, and a qPCR-based copy number assay can be used for screening. IHC is also a valid and practical method for evaluating FGFR2, considering frequent heterogeneity.

摘要

据报道，纤维母细胞生长因子受体2（FGFR2）扩增是胃癌治疗的一个靶标。然而，目前尚缺乏理想的组织来源和方法用于评估 FGFR2。用实时定量聚合酶链反应（qPCR）方法，分别比较冰冻组织和福尔马林固定及石蜡包埋（FFPE）组织、活检标本和手术标本的拷贝数。将IV期胃癌活检标本中qPCR和IHC的结果与FISH结果相关联，来验证胃癌手术标本中qPCR和IHC与FISH结果的关联性。

FFPE组织适合做qPCR检测，而且活检标本相当于或优于手术标本。不论是活检还是手术标本，qPCR检测拷贝数大于8时，qPCR和IHC结果显示与FISH相关性很好，活检标本中IHC检测FGFR2阳性大于5%、手术标本中IHC检测FGFR2阳性大于10%时qPCR和IHC结果显示与FISH相关性很好。IV期胃癌中FGFR2扩增发生率为6.6%，其中有42%表现为异质性扩增和过表达。即使是存在异质性的病例，IHC仍显示与FISH相关性很好。

FFPE活检组织标本适合评估胃癌中的FGFR2，qPCR拷贝数检测可用于筛选。尽管常存在异质性表达，IHC仍是一种有效且实用评估胃癌FGFR2的方法。