Division of Urology, Princess Margaret Hospital, Toronto, Ontario, Canada.
J Urol. 2012 Jan;187(1):310-4. doi: 10.1016/j.juro.2011.09.008. Epub 2011 Nov 17.
Stage pT1 bladder cancer comprises a heterogeneous group of tumors for which different management options are advocated. FGFR3 mutations are linked to favorable (low grade/stage) pTa bladder cancer while altered P53 is common in cases of high grade, muscle invasive (pT2 or greater) bladder cancer. We determined the frequency of FGFR3 mutations and P53 alterations in patients with pT1 bladder cancer and correlated these data to histopathological variables and clinical outcomes.
We included 132 patients with primary pT1 bladder cancer from a total of 2 academic centers. A uropathologist reviewed the slides for grade and confirmed the pT1 diagnosis. FGFR3 mutation status was examined by SNaPshot® analysis and P53 expression was determined by standard immunohistochemistry. Kaplan-Meier and multivariate analyses were used to assess progression.
FGFR3 mutations were detected in 37 of 132 pT1 bladder cancer cases (28%) and altered P53 was seen in 71 (54%). Only 8% of patients had the 2 molecular alterations (p = 0.001). FGFR3 mutation correlated with lower grade and altered P53 correlated with high grade pT1 bladder cancer. Median followup was 6.5 years. FGFR3 mutation status and carcinoma in situ were significant for predicting progression on univariate and multivariate analyses but P53 status was not.
FGFR3 mutations selectively identify patients with pT1 bladder cancer who have favorable disease characteristics. Further study may confirm that FGFR3 identifies those who would benefit from a conservative approach to the disease.
pT1 期膀胱癌包含一组异质性肿瘤，针对这些肿瘤，不同的治疗方法已被推荐。FGFR3 突变与低级别/分期（pTa）膀胱癌相关，而 P53 改变常见于高级别、肌层浸润（pT2 或更高）膀胱癌。我们确定了 FGFR3 突变和 P53 改变在 pT1 期膀胱癌患者中的发生率，并将这些数据与组织病理学变量和临床结果相关联。
我们纳入了来自两个学术中心的 132 例原发性 pT1 期膀胱癌患者。泌尿科病理学家对肿瘤切片进行分级并确认 pT1 诊断。通过 SNaPshot®分析检测 FGFR3 突变状态，通过标准免疫组化检测 P53 表达。采用 Kaplan-Meier 和多变量分析评估进展。
在 132 例 pT1 膀胱癌病例中，检测到 37 例（28%）存在 FGFR3 突变，71 例（54%）存在 P53 改变。仅有 8%的患者存在这 2 种分子改变（p = 0.001）。FGFR3 突变与低级别相关，而 P53 改变与高级别 pT1 膀胱癌相关。中位随访时间为 6.5 年。FGFR3 突变状态和原位癌在单变量和多变量分析中均是预测进展的显著因素，但 P53 状态不是。
FGFR3 突变选择性地识别出具有有利疾病特征的 pT1 期膀胱癌患者。进一步的研究可能证实 FGFR3 可识别出那些受益于疾病保守治疗的患者。
