Jantip Jariya, Tanthanuch Montira, Kanngurn Samornmas, Karnchanawanichkul Watid, Pripatnanont Choosak, Sangkhathat Surasak, Thongsuksai Paramee
Department of Biomedical Science, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.
J Med Assoc Thai. 2013 Aug;96(8):976-83.
Determine the incidence of FGFR3 mutations in Thai patients with bladder transitional cell carcinoma (TCC), and evaluate their correlation with pathological characteristics.
One hundred twenty two frozen tissue samples from TCC patients were analyzed for mutations in exons 7, 10, and 15 of FGFR3 by polymerase chain reaction and direct DNA sequencing.
FGFR3 mutations were detected in 22 of 122 cases (18%) studied, all of which were found within previously identified hotspots, including S249C (13 cases; 59%) and R248C (4 cases; 18%) in exon 7, and Y375C (5 cases; 23%) in exon 10, but no mutations in exon 15. Sixty-five patients (53%) were categorized as non-muscle-invasive TCC (pTa-pT1). The incidence of mutations is significantly higher in non-muscle-invasive tumors (28%) compared to the muscle-invading group (7%) (p < 0.01). Patients with grade (G) 1 TCC have significantly higher mutation frequency (40%) compared to other grades (4%) (p < 0.01). When T stage and grade were considered together, mutations were most commonly found in Ta-T1/G1 TCC (18/45 cases, 40%). Mean follow-up period was 45.1 months. Two-year and four-year overall survival (OS) was 70% and 56% respectively. Three-year OS in non-muscle-invasive TCC (80%) is significantly higher than that of muscle invading TCC (41%) (p < 0.01). However three-year OS in cases with an FGFR3 mutation (73%) is not significantly different from cases without a mutation (61%). In 16 cases with an FGFR3 mutation and recurrent disease, no mutations were detected in metachronous disease.
The overall incidence of FGFR3 mutations in Thai patients with TCC was lower than similar reports from other ethnic groups. In the presented cases, although FGFR3 mutations were frequently detected in low-grade, non-muscle-invasive TCC, identical mutation was not conserved in metachronous disease, thereby precluding the use of this marker in detection of tumor recurrence.
确定泰国膀胱移行细胞癌（TCC）患者中FGFR3突变的发生率，并评估其与病理特征的相关性。
采用聚合酶链反应和直接DNA测序法，对122例TCC患者的冷冻组织样本进行FGFR3第7、10和15外显子突变分析。
在122例研究病例中的22例（18%）检测到FGFR3突变，所有突变均在先前确定的热点区域内，包括第7外显子的S249C（13例；59%）和R248C（4例；18%），以及第10外显子的Y375C（5例；23%），但第15外显子未发现突变。65例患者（53%）被归类为非肌层浸润性TCC（pTa-pT1）。非肌层浸润性肿瘤的突变发生率（28%）显著高于肌层浸润性组（7%）（p<0.01）。1级TCC患者的突变频率（40%）显著高于其他分级（4%）（p<0.01）。当同时考虑T分期和分级时，突变最常见于Ta-T1/G1 TCC（18/45例，40%）。平均随访期为45.1个月。两年和四年总生存率（OS）分别为70%和56%。非肌层浸润性TCC的三年OS（80%）显著高于肌层浸润性TCC（41%）（p<0.01）。然而，FGFR3突变病例的三年OS（73%）与无突变病例（61%）无显著差异。在16例FGFR3突变且复发的病例中，异时性疾病未检测到突变。
泰国TCC患者中FGFR3突变的总体发生率低于其他种族的类似报道。在本研究病例中，尽管FGFR3突变在低级别、非肌层浸润性TCC中经常检测到，但异时性疾病中未保留相同突变，因此不能将该标志物用于肿瘤复发的检测。
