GATA3基因扩增与非侵袭性膀胱尿路上皮癌的高级别病变相关，但与患者预后无关。

GATA3 amplification is associated with high grade disease in non-invasive urothelial bladder cancer but unrelated to patient prognosis.

作者信息

Plage Henning, Frericks Adrian, Hofbauer Sebastian, Furlano Kira, Weinberger Sarah, Roßner Florian, Schallenberg Simon, Elezkurtaj Sefer, Lennartz Maximilian, Marx Andreas, Samtleben Henrik, Fisch Margit, Rink Michael, Slojewski Marcin, Kaczmarek Krystian, Ecke Thorsten, Koch Stefan, Simon Ronald, Sauter Guido, Zecha Henrik, Weischenfeldt Joachim, Klatte Tobias, Minner Sarah, Horst David, Schlomm Thorsten, Kluth Martina

机构信息

Department of Urology, Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.

Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

出版信息

BMC Urol. 2025 Feb 20;25(1):37. doi: 10.1186/s12894-025-01704-y.

DOI:10.1186/s12894-025-01704-y

PMID:39979991

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11841250/

Abstract

PURPOSE

We aimed to assess the impact of GATA3 binding protein (GATA3) gene copy number alterations on tumor aggressiveness, patient prognosis, and GATA3 protein expression in a large urothelial bladder cancer cohort.

METHODS

A tissue microarray containing over 2,700 urothelial bladder cancers (pTa-pT4) was analyzed retrospectively using dual-labeling fluorescence in-situ hybridization (FISH) with probes for GATA3 (10p14) and centromere 10. GATA3 copy number gains were categorized as GATA3 elevation (ratio GATA3/centromere ≥ 2/≤4), low-level amplification (ratio > 4/≤12), and high-level amplification (ratio > 12) and deletions were divided between homozygous and heterozygous.

RESULTS

GATA3 copy number gain was detected in 9.9% of 2,213 interpretable tumors, including 2.0% with GATA3 elevation, 3.2% with low-level amplification, and 4.7% with high-level amplification. The frequency of high-level amplification increased from pTa G2 low (0%) to pTa G3 tumors (12% [CI 0.07;0.21]; p < 0.0001 pTa G2 low vs. pTaG2 high) but decreased in advanced-stage carcinomas pT2-4 with 5.4% [CI 0.07;0.21] (p < 0.0001, pTa vs. pT2-4). In muscle-invasive carcinomas, GATA3 amplification was not linked to tumor aggressiveness or patient survival. Overall, no homozygous GATA3 deletion was detected and heterozygous GATA3 deletion was only observed in 1.1%; of 1,432 pT2-4 tumors without any association to cancer progression. While GATA3 copy number was significantly correlated with GATA3 expression (p < 0.0001), the relationship was not strong. Only 2.3% of GATA3-negative cancers had a deletion, and 42.1% of strong GATA3-expressing cancers exhibited high-level amplification.

CONCLUSION

High-level GATA3 amplification is common in urothelial bladder cancer and correlates with grade progression in pTa tumors, while GATA3 deletion is rare. Neither amplification nor deletion appears to be the primary driver of GATA3 expression dysregulation.

CLINICAL TRIAL NUMBER

Not applicable.

摘要

目的

我们旨在评估GATA3结合蛋白（GATA3）基因拷贝数改变对一大群膀胱尿路上皮癌患者的肿瘤侵袭性、患者预后以及GATA3蛋白表达的影响。

方法

使用针对GATA3（10p14）和10号染色体着丝粒的探针，通过双标记荧光原位杂交（FISH）对包含2700多个膀胱尿路上皮癌（pTa - pT4）的组织芯片进行回顾性分析。GATA3拷贝数增加分为GATA3升高（GATA3/着丝粒比率≥2/≤4）、低水平扩增（比率>4/≤12）和高水平扩增（比率>12），缺失分为纯合缺失和杂合缺失。

结果

在2213个可解释的肿瘤中，9.9%检测到GATA3拷贝数增加，其中2.0%为GATA3升高，3.2%为低水平扩增，4.7%为高水平扩增。高水平扩增的频率从pTa G2低级别肿瘤（0%）增加到pTa G3肿瘤（12%[CI 0.07;0.21]；p<0.0001，pTa G2低级别 vs. pTaG2高级别），但在晚期癌pT2 - 4中降低，为5.4%[CI 0.07;0.21]（p<0.0001，pTa vs. pT2 - 4）。在肌层浸润性癌中，GATA3扩增与肿瘤侵袭性或患者生存率无关。总体而言，未检测到纯合GATA3缺失，仅在1.1%的肿瘤中观察到杂合GATA3缺失；在1432个pT2 - 4肿瘤中，与癌症进展无任何关联。虽然GATA3拷贝数与GATA3表达显著相关（p<0.0001），但这种关系并不强。仅2.3%的GATA3阴性癌症存在缺失，42.1%的GATA3强表达癌症表现出高水平扩增。