Rieger-Christ Kimberly M, Mourtzinos Arthur, Lee Peter J, Zagha Ralph M, Cain Jason, Silverman Mark, Libertino John A, Summerhayes Ian C
Cell and Molecular Biology Laboratory, Robert E. Wise M. D. Research and Education Institute, Burlington, Massachusetts, USA.
Cancer. 2003 Aug 15;98(4):737-44. doi: 10.1002/cncr.11536.
Mutations in fibroblast growth factor 3 receptor (FGFR3) are frequent events in low-grade bladder tumors. To assess the potential utility of the detection of FGFR3 mutations in a screening modality, the authors analyzed urine sediment DNA samples from 192 patients in a retrospective study.
Urine sediment DNA samples from 192 patients were prepared. Seventy-two patients had undergone transurethral resection (TURBT group) of mainly Ta lesions and 120 patients had undergone cystectomy (cystectomy group). The majority of patients in the cystectomy group had more advanced tumors compared with patients in the TURBT group. DNA preparations were screened for FGFR3 mutations in exons 7, 10, and 15 using single-strand conformation polymorphism (SSCP) and DNA sequencing.
Using SSCP, 67% of patients in the TURBT group and 28% in the cystectomy group displayed FGFR3 mutations. Comparative analysis of cytology results and FGFR3 mutational analysis were performed in 122 cases. Within the TURBT group, FGFR3 mutation analysis outperformed cytology. FGFR3 mutation analysis identified change in 68% of urine sediment DNA samples whereas cytology recorded the presence of tumor cells in 32% of the DNA samples. In the cystectomy group, cytology outperformed FGFR3 mutation analysis. Cytology recorded tumor detection in 90% of patients, while SSCP identified mutational change in 24%.
Combining FGFR3 mutation results with cytology in both groups correctly identified tumor presence in 105 of 122 (86%) of patients. The greater sensitivity of FGFR3 mutation detection over cytology in identifying the presence of low-grade, superficial bladder tumors represents a potential new tool to complement standard cytology in screening patients for bladder tumors and recurrent disease.
成纤维细胞生长因子3受体（FGFR3）突变在低级别膀胱肿瘤中很常见。为了评估检测FGFR3突变在一种筛查方式中的潜在效用，作者在一项回顾性研究中分析了192例患者的尿沉渣DNA样本。
制备了192例患者的尿沉渣DNA样本。72例患者接受了主要为Ta病变的经尿道膀胱肿瘤切除术（TURBT组），120例患者接受了膀胱切除术（膀胱切除术组）。与TURBT组患者相比，膀胱切除术组的大多数患者肿瘤分期更晚。使用单链构象多态性（SSCP）和DNA测序对DNA样本进行FGFR3外显子7、10和15的突变筛查。
使用SSCP，TURBT组67%的患者和膀胱切除术组28%的患者显示FGFR3突变。对122例患者进行了细胞学结果与FGFR3突变分析的对比。在TURBT组中，FGFR3突变分析优于细胞学检查。FGFR3突变分析在68%的尿沉渣DNA样本中发现了变化，而细胞学检查在32%的DNA样本中检测到肿瘤细胞。在膀胱切除术组中，细胞学检查优于FGFR3突变分析。细胞学检查在90%的患者中检测到肿瘤，而SSCP在24%的患者中发现了突变变化。
在两组中将FGFR3突变结果与细胞学检查相结合，在122例患者中的105例（86%）中正确识别出肿瘤的存在。在识别低级别、浅表性膀胱肿瘤的存在方面，FGFR3突变检测比细胞学检查具有更高的敏感性，这代表着一种潜在的新工具，可在膀胱肿瘤和复发性疾病患者的筛查中补充标准细胞学检查。
