Department of Urology, St. James's University Hospital, Leeds, United Kingdom.
Department of Histopathology, St. James's University Hospital, Leeds, United Kingdom.
J Urol. 2015 Jan;193(1):325-30. doi: 10.1016/j.juro.2014.06.026. Epub 2014 Jun 13.
FGFR3 is considered a good therapeutic target for bladder cancer. However, to our knowledge it is unknown whether the FGFR3 status of primary tumors is a surrogate for related metastases, which must be targeted by FGFR targeted systemic therapies. We assessed FGFR3 protein expression in primary bladder tumors and matched nodal metastases.
We examined matched primary tumor and nodal metastases from 150 patients with bladder cancer clinically staged as N0M0. Four samples per patient were incorporated into a tissue microarray and FGFR3 expression was assessed by immunohistochemistry. FGFR3 expression was tested for an association with categorical clinical data using the Fisher exact test, and with overall and recurrence-free survival by Kaplan-Meier analysis.
Duplicate spots from primary tumors and lymph node metastases were highly concordant (OR 8.6 and 16.7, respectively, each p <0.001). Overall FGFR protein expression levels did not differ between primary and metastatic lesions (p = 0.78). Up-regulated expression was recorded in 53 of 106 evaluable primary tumor spots and 56 matched metastases. Concordance of FGFR3 expression levels in 79 matched primary tumor and metastasis specimens was high (OR 8.45, p <0.001). In 15 and 12 patients expression was up-regulated in only metastasis and in only the primary tumor, respectively. Overall and recurrence-free survival was not related to FGFR3 expression.
FGFR3 expression in matched primary and metastasized bladder cancer specimens showed good but not absolute concordance. Thus, in most patients primary tumor FGFR3 status can guide the selection of FGFR targeted therapy.
FGFR3 被认为是膀胱癌的一个很好的治疗靶点。然而,据我们所知,原发性肿瘤的 FGFR3 状态是否是相关转移灶的替代物尚不清楚,而转移灶必须通过 FGFR 靶向的系统治疗来靶向。我们评估了原发性膀胱癌肿瘤和匹配的淋巴结转移中的 FGFR3 蛋白表达。
我们检查了 150 例临床分期为 N0M0 的膀胱癌患者的匹配原发性肿瘤和淋巴结转移。每位患者的 4 个样本被纳入组织微阵列中,并通过免疫组织化学评估 FGFR3 表达。使用 Fisher 确切检验评估 FGFR3 表达与分类临床数据的关联,并通过 Kaplan-Meier 分析评估与总生存期和无复发生存期的关系。
原发性肿瘤和淋巴结转移的重复点高度一致(OR 分别为 8.6 和 16.7,p 值均 <0.001)。原发性和转移性病变之间的总体 FGFR 蛋白表达水平没有差异(p = 0.78)。在可评估的 106 个原发性肿瘤点中的 53 个和 56 个匹配的转移瘤中有上调表达。79 对匹配的原发性肿瘤和转移标本中 FGFR3 表达水平的一致性很高(OR 8.45,p <0.001)。在 15 例和 12 例患者中,仅在转移灶和仅在原发性肿瘤中表达上调。总生存期和无复发生存期与 FGFR3 表达无关。
匹配的原发性和转移性膀胱癌标本中的 FGFR3 表达显示出良好但并非绝对一致。因此,在大多数患者中,原发性肿瘤 FGFR3 状态可以指导 FGFR 靶向治疗的选择。