Department of Pathology and Laboratory Medicine, Brown University Warren Alpert Medical School, Lifespan Academic Medical Center, and the Legorreta Cancer Center at Brown University, Providence, Rhode Island; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Department of Morphological Sciences, University of Cordoba Medical School, Cordoba, Spain.
Mod Pathol. 2023 Jul;36(7):100151. doi: 10.1016/j.modpat.2023.100151. Epub 2023 Mar 9.
The precursor nature of papillary urothelial hyperplasia of the urinary bladder is uncertain. In this study, we investigated the telomerase reverse transcriptase (TERT) promoter and fibroblast growth factor receptor 3 (FGFR3) mutations in 82 patients with papillary urothelial hyperplasia lesions. Thirty-eight patients presented with papillary urothelial hyperplasia and concurrent noninvasive papillary urothelial carcinoma, and 44 patients presented with de novo papillary urothelial hyperplasia. The prevalence of the TERT promoter and FGFR3 mutations is compared between de novo papillary urothelial hyperplasia and those with concurrent papillary urothelial carcinoma. Mutational concordance between papillary urothelial hyperplasia and concurrent carcinoma was also compared. The TERT promoter mutations were detected in 44% (36/82) of papillary urothelial hyperplasia, including 23 (23/38, 61%) papillary urothelial hyperplasia with urothelial carcinoma and 13 (13/44, 29%) de novo papillary urothelial hyperplasia. The overall concordance of TERT promoter mutation status between papillary urothelial hyperplasia and concurrent urothelial carcinoma was 76%. The overall FGFR3 mutation rate of papillary urothelial hyperplasia was 23% (19/82). FGFR3 mutations were detected in 11 patients with papillary urothelial hyperplasia and concurrent urothelial carcinoma (11/38, 29%) and 8 patients with de novo papillary urothelial hyperplasia (8/44, 18%). Identical FGFR3 mutation status was detected in both papillary urothelial hyperplasia and urothelial carcinoma components in all 11 patients with FGFR3 mutations. Our findings provide strong evidence of a genetic association between papillary urothelial hyperplasia and urothelial carcinoma. High frequency of TERT promoter and FGFR3 mutations suggests the precursor role of papillary urothelial hyperplasia in urothelial carcinogenesis.
膀胱乳头状尿路上皮增生的前体性质尚不确定。在这项研究中，我们调查了 82 例乳头状尿路上皮增生病变患者的端粒酶逆转录酶（TERT）启动子和成纤维细胞生长因子受体 3（FGFR3）突变。38 例患者表现为乳头状尿路上皮增生伴同时性非浸润性乳头状尿路上皮癌，44 例患者表现为初发性乳头状尿路上皮增生。比较了初发性乳头状尿路上皮增生与同时性乳头状尿路上皮癌之间 TERT 启动子和 FGFR3 突变的发生率。还比较了乳头状尿路上皮增生与同时性癌之间的突变一致性。在 82 例乳头状尿路上皮增生中，检测到 TERT 启动子突变 44%（36/82），其中 23 例（23/38，61%）伴尿路上皮癌的乳头状尿路上皮增生和 13 例（13/44，29%）初发性乳头状尿路上皮增生。乳头状尿路上皮增生与同时性尿路上皮癌之间 TERT 启动子突变状态的总一致性为 76%。乳头状尿路上皮增生的总 FGFR3 突变率为 23%（19/82）。在 11 例伴有乳头状尿路上皮癌的患者中检测到 FGFR3 突变（11/38，29%）和 8 例初发性乳头状尿路上皮增生患者（8/44，18%）。在所有 11 例 FGFR3 突变患者中，FGFR3 突变在乳头状尿路上皮增生和尿路上皮癌成分中均检测到相同的突变状态。我们的研究结果提供了强有力的证据，证明乳头状尿路上皮增生与尿路上皮癌之间存在遗传关联。TERT 启动子和 FGFR3 突变的高频率提示乳头状尿路上皮增生在尿路上皮癌发生中的前体作用。
