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成纤维细胞生长因子受体1蛋白(FGFR1)作为人表皮受体2蛋白(HER2)过表达的管腔B型乳腺癌患者潜在的预后和预测标志物。

Fibroblast growth factor receptor 1 protein (FGFR1) as potential prognostic and predictive marker in patients with luminal B breast cancers overexpressing human epidermal receptor 2 protein (HER2).

作者信息

Amina Belhadj, Lynda Addou Klouche, Sonia Seddiki, Adel Belhadj, Jelloul Benammar H, Miloud Medjamia, Tewfik Sahraoui

机构信息

Biology of Development and Differentiation Laboratory, Oran 1 University, Ahmed Ben Bella, Oran, Algeria.

Biotoxicology Laboratory, Sidi Bel Abbes University, Oran, Algeria.

出版信息

Indian J Pathol Microbiol. 2021 Apr-Jun;64(2):254-260. doi: 10.4103/IJPM.IJPM_87_20.

Abstract

CONTEXT

Breast cancer is the most common cause of cancer mortality among women worldwide. It is a heterogeneous disease partly responsible for treatment failure in luminal B patients. Deregulation of fibroblast growth factor signaling has been found and its therapeutic/prognostic value is explored.

AIMS

Most of the research has studied the FGFR1 gene while our study explored its protein expression by immunohistochemestry and examined the association with clinicopathological features, different molecular subtypes and survival.

SUBJECTS AND METHODS

Formalin-fixed and paraffin-embedded samples of invasive breast carcinomas were used to analyze FGFR1 expression. FGFR 1 was scored by percentage and intensity of cell cytoplasm staining, correlations were investigated and survival curves were constructed.

STATISTICAL ANALYSIS USED

Chi-square test was used to assess the relationship between the marker expression and the clinicopathological characteristics. Overall specific survival curves were estimated using the Kaplan-Meier method and statistical significance was assessed using the log-rank test.

RESULTS

FGFR1 was associated at different staining threshold cut-offs with tumor size (P = 0.002), infiltrating lymph node (P = 0.022), distant metastasis (P = 0.003), positive estrogen receptor (P = 0.000), HER2 overexpression (P = 0.044) and luminal phenotypes (P = 0.026). The results also emphasize FGFR1 correlation expression with distant metastasis in luminal B tumors (P = 0.035) but not with luminal A and with overexpressed HER2 protein in both luminal tumors. FGFR1 expression affect luminal B patients survival with poor outcome.

CONCLUSIONS

FGFR1 expression may serve as a prognostic and predictive factor in luminal breast cancers, it can also be considered as a potential therapeutic target in luminal B cases.

摘要

背景

乳腺癌是全球女性癌症死亡的最常见原因。它是一种异质性疾病,部分导致了管腔B型患者的治疗失败。已发现成纤维细胞生长因子信号传导失调,并对其治疗/预后价值进行了探索。

目的

大多数研究聚焦于FGFR1基因,而我们的研究通过免疫组织化学探究其蛋白表达,并检查其与临床病理特征、不同分子亚型及生存率的关联。

对象与方法

采用福尔马林固定、石蜡包埋的浸润性乳腺癌样本分析FGFR1表达。通过细胞质染色的百分比和强度对FGFR1进行评分,研究相关性并构建生存曲线。

所用统计分析方法

采用卡方检验评估标志物表达与临床病理特征之间的关系。使用Kaplan-Meier方法估计总体特异性生存曲线,并使用对数秩检验评估统计学意义。

结果

在不同染色阈值下,FGFR1与肿瘤大小(P = 0.002)、浸润淋巴结(P = 0.022)、远处转移(P = 0.003)、雌激素受体阳性(P = 0.000)、HER2过表达(P = 0.044)和管腔表型(P = 0.026)相关。结果还强调FGFR1在管腔B型肿瘤中与远处转移的相关性表达(P = 0.035),但在管腔A型肿瘤中无相关性,且在两种管腔型肿瘤中均与HER2蛋白过表达相关。FGFR1表达影响管腔B型患者的生存,预后较差。

结论

FGFR1表达可能作为管腔型乳腺癌的预后和预测因子,在管腔B型病例中也可被视为潜在的治疗靶点。

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