Diffusive Ki67 and vimentin are associated with worse recurrence-free survival of upper tract urothelial carcinoma: A retrospective cohort study from bench to bedside

Abstract

Objectives: This study aimed to determine the prognostic values of Ki67 and vimentin in upper tract urothelial carcinoma (UTUC) after extirpative surgery.

Methods and materials: Between 2014 and 2019, patients diagnosed with UTUC and receiving radical nephroureterectomy were included retrospectively. Nuclear MIB-1 clones and cytoplasmic VIM 3B4 clones were used to assess Ki67 and vimentin levels, respectively. A unified reading protocol was applied, and the expression level was read by a single pathologist. Receiver operating characteristic curves were utilized to determine the best threshold for Ki67 and vimentin regarding recurrence, and this level was set as the diffusive level. The outcome of recurrence-free survival (RFS) was analyzed via a Cox regression model with univariable and multivariable approaches. Survival outcomes were analyzed via Kaplan-Meier (KM) curves.

Results: A total of 247 patients were included, and the mean follow-up was 29.90 ± 6.80 months. Diffusive thresholds were 17.5% for both Ki67 and vimentin. Under multivariable Cox regression, diffusive Ki67 (hazard ratio: 4.20 [2.39-7.37], P < 0.001) and diffusive vimentin (hazard ratio: 5.34 [3.10-9.22], P < 0.001) were significant prognostic indicators of worse RFS. Diffusive Ki67 was accompanied by diffusive vimentin (chi square with Yates' correction, P = 0.015), and vice versa. In the KM curve, there was no difference between diffusive Ki67/nondiffusive vimentin and nondiffusive Ki67/diffusive vimentin (log-rank test, P = 0.073). Significant differences (log-rank test, P < 0.001) were seen in different combinations of diffusive Ki67/vimentin (Mean RFS: 19.76 [18.56-20.96] months), only one diffusive in Ki67 or vimentin (Mean RFS: 22.94 [21.88-24.00] months), and nondiffusive Ki67/vimentin (Mean RFS: 32.96 [32.43-33.50] months).

Conclusions: Diffusive Ki67 and vimentin were related to each other, and they exerted equivalent and synergic effects on predicting worse RFS in UTUC.

Keywords: Carcinoma, transitional cell/pathology; Disease-free survival; Epithelial-mesenchymal transition; Ki-67 antigen/analysis; Neoplasm invasiveness.