Lamy A, Gobet F, Laurent M, Blanchard F, Varin C, Moulin C, Andreou A, Frebourg T, Pfister C
Department of Pathology, Rouen University Hospital, 1 rue de Germont, 76031 Rouen Cedex, North-West Canceropole, France.
J Urol. 2006 Dec;176(6 Pt 1):2686-9. doi: 10.1016/j.juro.2006.07.132.
On a routine basis we performed systematic molecular screening for FGFR3 and TP53 mutations in 121 bladder tumors. We then specifically analyzed the predictive value of the recurrence of FGFR3 and TP53 genotypes in superficial lesions.
The FGFR3 gene was analyzed by direct sequencing of exons 7, 10 and 15, whereas TP53 status was determined using the p53 functional assay in yeast.
We identified a missense FGFR3 mutation in 66% of pTa, 26% of pT1 and 12% of pT2 tumors. Of activating FGFR3 mutations 54% and 85% were found in low G1 and intermediate G2 grade tumors, respectively, but in only 20% of high grade G3 tumors. We detected inactivating TP53 mutations in 10% of pTa, 42% of pT1 and 58% of pT2 tumors. Moreover, TP53 mutations were found only in 23% of grade G1 and 3% of grade G2 tumors but in 44% of high grade G3 tumors. When the 2 genotypes were combined, we observed that 58% of pTa tumors had the (mutant FGFR3, WT TP53) genotype, whereas 58% of invasive lesions harbored the inverse genotype (WT FGFR3, mutant TP53). The (mutant FGFR3, WT TP53) genotype and the (WT FGFR3, mutant TP53) genotype were detected in 23% and 38% of pT1G3 tumors, respectively. In the subgroup of 92 patients with superficial pTa-T1 bladder tumors we did not find that the TP53 or FGFR3 genotype alone or combined had a predictive value for tumor recurrence.
Our data again represent solid proof for the pivotal role of FGFR3 and TP53 mutations in superficial and invasive bladder tumors, respectively. However, other molecular markers should be identified for borderline pT1G3 bladder tumors, which are probably at the crossroads of these 2 distinct molecular pathways.
我们定期对121例膀胱肿瘤进行FGFR3和TP53突变的系统分子筛查。然后，我们专门分析了FGFR3和TP53基因型在浅表病变中对复发的预测价值。
通过对第7、10和15外显子进行直接测序分析FGFR3基因，而使用酵母中的p53功能检测法确定TP53状态。
我们在66%的pTa肿瘤、26%的pT1肿瘤和12%的pT2肿瘤中发现了FGFR3错义突变。在低G1级和中等G2级肿瘤中分别发现54%和85%的激活型FGFR3突变，但在高级别G3肿瘤中仅发现20%。我们在10%的pTa肿瘤、42%的pT1肿瘤和58%的pT2肿瘤中检测到失活型TP53突变。此外，仅在23%的G1级肿瘤和3%的G2级肿瘤中发现TP53突变，但在44%的高级别G3肿瘤中发现。当将这两种基因型结合起来时，我们观察到58%的pTa肿瘤具有（突变型FGFR3，野生型TP53）基因型，而58%的浸润性病变具有相反的基因型（野生型FGFR3，突变型TP53）。在pT1G3肿瘤中，分别有23%和38%检测到（突变型FGFR3，野生型TP53）基因型和（野生型FGFR3，突变型TP53）基因型。在92例浅表性pTa-T1膀胱肿瘤患者亚组中，我们未发现单独或联合的TP53或FGFR3基因型对肿瘤复发具有预测价值。
我们的数据再次有力证明了FGFR3和TP53突变分别在浅表性和浸润性膀胱肿瘤中的关键作用。然而，对于临界性pT1G3膀胱肿瘤，可能处于这两种不同分子途径的交叉点，应确定其他分子标志物。
