Spatial heterogeneity of FGFR2b in gastric cancer: a comparative analysis of primary tumors and peritoneal dissemination.

IF 3.1 3区 医学 Q1 PATHOLOGY
Haruki Ogawa, Hiroyuki Abe, Koichi Yagi, Yoshifumi Baba, Yasuyuki Seto, Tetsuo Ushiku
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引用次数: 0

Abstract

Gastric cancer with peritoneal dissemination (PD) confers poor prognosis and limited treatment options. FGFR2b-targeted therapy has emerged as a potential approach for FGFR2b-positive tumors. However, the expression and amplification status of FGFR2b in PD remains poorly characterized. This study aimed to investigate FGFR2b expression and gene amplification in matched primary tumors and PD tissues from gastric cancer patients, and to evaluate their association with established biomarkers including HER2, CLDN18, and PD-L1. Immunohistochemistry (IHC) for FGFR2b was performed on matched primary and PD tissues from 84 patients. FGFR2 FISH was conducted in IHC-positive cases. FGFR2b expression was detected in 7.1% (6/84) of primary tumors and 4.8% (4/84) of PD samples. Expression was highly heterogeneous; only one case was FGFR2b-positive in both primary and PD tissues. FGFR2 amplification was found in 6 of 10 IHC-positive samples, and not observed in IHC-negative samples. FGFR2b status showed no significant correlation with HER2, CLDN18, or PD-L1. FGFR2b expression in gastric cancer is spatially heterogeneous and discordant between primary tumors and PD. It may be preferable to test both primary tumor and PD tissue, if available, to better identify candidates for FGFR2b-targeted therapy. FGFR2b represents a potential therapeutic target for a subset of PD-positive gastric cancers lacking other biomarker expression.

FGFR2b在胃癌中的空间异质性:原发肿瘤和腹膜传播的比较分析
胃癌伴腹膜播散(PD)预后差,治疗选择有限。fgfr2b靶向治疗已成为fgfr2b阳性肿瘤的潜在治疗方法。然而,FGFR2b在PD中的表达和扩增状态仍然不清楚。本研究旨在研究FGFR2b在胃癌患者匹配的原发肿瘤和PD组织中的表达和基因扩增,并评估其与HER2、CLDN18和PD- l1等已建立的生物标志物的相关性。对84例患者的匹配原发和PD组织进行FGFR2b免疫组化(IHC)。FGFR2 FISH在ihc阳性病例中进行。在7.1%(6/84)的原发肿瘤和4.8%(4/84)的PD样本中检测到FGFR2b表达。表达高度异质;只有1例在原发组织和PD组织中均为fgfr2b阳性。在10个ihc阳性样本中有6个发现FGFR2扩增,而在ihc阴性样本中未观察到。FGFR2b状态与HER2、CLDN18或PD-L1无显著相关性。FGFR2b在胃癌中的表达在原发肿瘤和PD之间具有空间异质性和不一致性。如果可能的话,最好同时检测原发肿瘤和PD组织,以便更好地确定fgfr2b靶向治疗的候选者。FGFR2b代表了缺乏其他生物标志物表达的pd阳性胃癌亚群的潜在治疗靶点。
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来源期刊
Virchows Archiv
Virchows Archiv 医学-病理学
CiteScore
7.40
自引率
2.90%
发文量
204
审稿时长
4-8 weeks
期刊介绍: Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.
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