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术前放化疗后残留直肠癌患者成纤维细胞生长因子受体2表达的临床意义:与KRAS或BRAF突变及微卫星不稳定性状态的关系

Clinical significance of fibroblast growth factor receptor 2 expression in patients with residual rectal cancer after preoperative chemoradiotherapy: relationship with KRAS or BRAF mutations and MSI status.

作者信息

Yoon Ghilsuk, Lee Hwayoung, Kim Jae-Hoon, Hur Keun, Seo An Na

机构信息

Department of Pathology, Kyungpook National University Medical Center, 807 Hogukno, Buk-gu, Daegu, 41404, Republic of Korea.

Department of Pathology, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, Republic of Korea.

出版信息

Tumour Biol. 2016 Aug;37(8):10209-18. doi: 10.1007/s13277-016-4899-z. Epub 2016 Jan 30.

Abstract

This study was designed to determine the prognostic impact and clinical significance of FGFR2 in residual disease after preoperative chemoradiotherapy (CRT) in patients with rectal cancer. The surgical specimens of 145 patients with residual rectal cancer after preoperative CRT were analyzed. To evaluate FGFR2 expression, immunohistochemistry was performed on whole section tissues. KRAS exon 2 (codon 12 and 13), BRAF V600E mutational status, and microsatellite instability (MSI) were determined using polymerase chain reactions. Of the eligible 141 patients, FGFR2 over-expression was observed in 75.9 % (n = 107) and was correlated with perineural invasion (P = 0.005) and inferior tumor regression grading (TRG) (P = 0.009). However, FGFR2 expression had no relationship with KRAS and BRAF mutation results or with MSI results. On univariate analysis, FGFR2 over-expression was significantly associated with worse rectal cancer-specific survival (RCSS) (P = 0.005) and disease-free survival (DFS) (P = 0.035). However, multivariate analysis revealed that FGFR2 over-expression was not independently associated with RCSS and DFS (all P > 0.05). Although FGFR2 over-expression did not independently influence patient outcome, FGFR2 over-expression was associated with worse prognosis and inferior TRG. Our data may aid in understanding the therapeutic approaches targeting FGFR2 in patients with residual rectal cancer after preoperative CRT.

摘要

本研究旨在确定FGFR2在直肠癌患者术前放化疗(CRT)后残留病灶中的预后影响及临床意义。对145例术前CRT后残留直肠癌患者的手术标本进行了分析。为评估FGFR2表达,对全层组织进行了免疫组化。采用聚合酶链反应测定KRAS外显子2(密码子12和13)、BRAF V600E突变状态及微卫星不稳定性(MSI)。在符合条件的141例患者中,75.9%(n = 107)观察到FGFR2过表达,且与神经周围浸润(P = 0.005)和较差的肿瘤退缩分级(TRG)(P = 0.009)相关。然而,FGFR2表达与KRAS和BRAF突变结果或MSI结果无关。单因素分析显示,FGFR2过表达与较差的直肠癌特异性生存(RCSS)(P = 0.005)和无病生存(DFS)(P = 0.035)显著相关。然而,多因素分析显示,FGFR2过表达与RCSS和DFS无独立相关性(所有P > 0.05)。虽然FGFR2过表达并未独立影响患者预后,但FGFR2过表达与较差的预后和较低的TRG相关。我们的数据可能有助于理解术前CRT后残留直肠癌患者针对FGFR2的治疗方法。

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