Profiling the Molecular Characteristics and Transitions Through Upper Tract Tumor Origin, Bladder Recurrence, and Muscle Invasive Bladder Progression in Upper Tract Urothelial Carcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16809
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Keio University
• Principal Investigator: Shigeta Keisuke 慶應義塾大学, 医学部(信濃町), 訪問研究員 (10649875)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 上部尿路上皮癌 / 膀胱内再発 / CK5/6 / CK2０ / FGFR3 / P53

Outline of Final Research Achievements

Postoperative bladder recurrence in renal pelvic and ureteral cancer, sometimes progressing to MIBC, poses challenges. This study tracks molecular characteristics of primary cancer and bladder recurrences. Among 214 patients post-nephroureterectomy, 92 had intravesical recurrence. CK20 and FGFR3 were predictive markers for recurrence. FGFR3 positivity was higher (60.9%) in recurrence cases. MIBC progression was associated with elevated p53 mutant protein expression. Renal pelvic and ureteral cancers tend to recur intravesically, especially luminal-papillary types with CK20 and FGFR3 positivity. Recurrent bladder cancer inherits molecular features from the primary tumor, with additional p53 mutant protein expression linked to muscle invasion.

Free Research Field

上部尿路上皮癌

Academic Significance and Societal Importance of the Research Achievements

これまで腎盂尿管癌患者の膀胱内再発リスク因子において、臨床病理学的因子の報告は多数行われてきたが、分子サブタイプを加えた再発リスク因子に関する知見は皆無であった。
本研究から、CK20やFGFR3などの分子マーカーが膀胱内再発の予測因子となることが示されたこと、更にはp53変異蛋白の存在がMIBCへの進展と関連していたことから、分子サブタイプ別病理学的評価は、再発進展リスクの高い患者に対する治療方針の決定に重要な意義をい持つと考えている。また、将来的には腎盂尿管癌や膀胱内再発後患者における革新的創薬研究に寄与すると考える。