Immunohistochemical Expression of p53 and FGFR3 Predicts Response to Enfortumab Vedotin in Metastatic Urothelial Carcinoma

被引:0
作者
Nagata, Yujiro [1 ]
Minato, Akinori [1 ]
Aono, Hisami [1 ]
Kimuro, Rieko [1 ]
Higashijima, Katsuyoshi [1 ]
Tomisaki, Ikko [1 ]
Harada, Kenichi [1 ]
Miyamoto, Hiroshi [2 ,3 ]
Fujimoto, Naohiro [1 ,4 ]
机构
[1] Univ Occupat & Environm Hlth, Sch Med, Dept Urol, Kitakyushu 8078555, Japan
[2] Univ Rochester, Med Ctr, Dept Pathol, Rochester, NY 14642 USA
[3] Univ Rochester, Med Ctr, Lab Med & Urol, Rochester, NY 14642 USA
[4] Kurate Hosp, Dept Urol, Kurate 8071311, Japan
关键词
urothelial carcinoma; bladder cancer; upper urinary tract cancer; enfortumab vedotin; p53; FGFR3; MOLECULAR CLASSIFICATION; CELL-CARCINOMA; CANCER; BLADDER; MUTATIONS; GENE; OPPORTUNITIES; MULTICENTER; EFFICACY; CRITERIA;
D O I
10.3390/ijms251910348
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Locally advanced or metastatic urothelial carcinoma is a genomically and molecularly heterogeneous disease associated with various clinical outcomes. We aimed to evaluate the association between the status of p53/FGFR3 expression and the efficacy of enfortumab vedotin (EV) in metastatic urothelial carcinoma. We evaluated the association between p53 (abnormal vs. wild-type) or FGFR3 (high vs. low) expression determined by immunohistochemistry and response to EV in 28 patients with metastatic urothelial carcinoma. Overall, 60.7% showed abnormal p53, and 17.9% had high FGFR3 expression. The rates of objective response to EV were statistically higher in patients with abnormal p53 than in those with wild-type p53 (p = 0.038). Patients with pure urothelial carcinoma (n = 18) and low FGFR3 showed significantly better response to EV than those with high FGFR3. When the statuses of p53 and FGFR3 were combined, abnormal p53/low FGFR3 (vs. wild-type p53/high FGFR3) was strongly associated with favorable outcomes in both the entire cohort (p = 0.002) and in cases of pure urothelial carcinoma only (p = 0.023). Immunohistochemically abnormal p53 tumors were found to respond well to EV, while high FGFR3 tumors had a poorer response. Thus, p53 and FGFR3 are potential biomarkers for predicting response to EV treatment in patients with urothelial carcinoma.
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