Wang Xiang, Huang Jie, Xu Chen, Zhang Lili, Su Jieakesu, Liu Jia, Shen Licheng, Luan Lijuan, Hou Yingyong
Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
Virchows Arch. 2025 May 26. doi: 10.1007/s00428-024-03884-8.
Identification and verification of clinically actionable molecular variations to refine currently adopted risk-stratified treatment strategy for esophageal squamous cell carcinoma (ESCC) is urgently needed. Here, we evaluated FGFR3 amplification status by fluorescence in situ hybridization (FISH) performed on tissue microarrays and its prognostic value in 526 ESCC patients. FGFR3 amplification was found in 3.0% (16/526) of ESCC patients enrolled in this study cohort. Intratumor heterogeneity and metastatic heterogeneity of FGFR3 amplification were found in 10% (2/20) and 40% (2/5) FGFR3 amplified ESCC cases, respectively. No statistically significant associations were found between FGFR3 amplification status and common clinicopathological features. Survival analyses demonstrated that FGFR3 amplification was associated with a worse disease-free survival (DFS) and overall survival (OS) (DFS, P = 0.008; OS, P = 0.027). Univariate and multivariate analyses revealed that invasive depth was significantly associated with DFS (P = 0.001, HR: 1.498, 95% CI: 1.172-1.914) and OS (P = 0.002, HR: 1.482, 95% CI: 1.159-1.894), and FGFR3 amplification was significantly associated with DFS (P = 0.020, HR: 2.065, 95% CI: 1.120-3.808) and tend to associate with OS (P = 0.070, HR: 1.756, 95% CI: 0.954-3.233). Furthermore, when patients were stratified into stage I-II group and stage III-IV group, the adverse effect of FGFR3 amplification on prognosis was presented in stage III-IV patients (DFS, P = 0.0047; OS, P = 0.029) rather than stage I-II patients (DFS, P = 0.46; OS, P = 0.53), indicating that the prognostic value of FGFR3 amplification may relying on clinical stage. Our findings might provide a better understanding of the FGFR3 amplification status in ESCC patients and add further insights into its potential prognostic value.
迫切需要识别和验证具有临床可操作性的分子变异，以优化目前采用的食管鳞状细胞癌（ESCC）风险分层治疗策略。在此，我们通过对组织微阵列进行荧光原位杂交（FISH）评估了526例ESCC患者的FGFR3扩增状态及其预后价值。在本研究队列纳入的ESCC患者中，3.0%（16/526）检测到FGFR3扩增。在10%（2/20）的FGFR3扩增ESCC病例中发现了FGFR3扩增的肿瘤内异质性，在40%（2/5）的病例中发现了转移异质性。未发现FGFR3扩增状态与常见临床病理特征之间存在统计学显著关联。生存分析表明，FGFR3扩增与无病生存期（DFS）和总生存期（OS）较差相关（DFS，P = 0.008；OS，P = 0.027）。单因素和多因素分析显示，浸润深度与DFS（P = 0.001，HR：1.498，95%CI：1.172 - 1.914）和OS（P = 0.002，HR：1.482，95%CI：1.159 - 1.894）显著相关，FGFR3扩增与DFS（P = 0.020，HR：2.065，95%CI：1.120 - 3.808）显著相关，并倾向于与OS相关（P = 0.070，HR：1.756，95%CI：0.954 - 3.233）。此外，当患者分为I-II期组和III-IV期组时，FGFR3扩增对预后的不良影响在III-IV期患者中表现明显（DFS，P = 0.0047；OS，P = 0.029），而在I-II期患者中不明显（DFS，P = 0.46；OS，P = 0.53），这表明FGFR3扩增的预后价值可能依赖于临床分期。我们的研究结果可能有助于更好地了解ESCC患者的FGFR3扩增状态，并进一步深入了解其潜在的预后价值。
