Identification of Significant Prognostic Tissue Markers Associated with Survival in Upper Urinary Tract Urothelial Carcinoma Patients Treated with Radical Nephroureterectomy: A Retrospective Immunohistochemical Analysis Using Tissue Microarray

Abstract

The purpose of this study was to identify prognostic tissue markers for several survival outcomes after radical nephroureterectomy among patients with upper urinary tract urothelial carcinoma using tissue microarray and immunohistochemistry. Materials and Methods Retrospectively, data of 162 non-metastatic patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy between 2004 and 2016 were reviewed to determine intravesical recurrence-free survival (IVRFS), disease-free survival (DFS), and overall survival (OS). The expression of 27 tissue markers on a tissue microarray of radical nephroureterectomy samples and prognostic values of clinicopathological parameters were evaluated using immunohistochemistry and Cox proportional hazard models after adjusting for significant prognostic clinicopathological variables. The expression of all tissue markers was categorized into a binary group with continuous H-scores (0-300). Results Median follow-up was 53.4 months (range, 3.6 to 176.5 months); and, 58 (35.8%), 48 (29.6%), and 19 (11.7%) bladder recurrence, disease progression, and all cause death, respectively, were identified. After adjusting for significant clinicopathological factors including intravesical instillation for bladder recurrence-free survival, pathologic T category and intravesical instillation for disease progression-free survival , and pathologic T category for OS (p < 0.05), IVRFS was associated with epithelial cadherin (hazard ratio [HR], 0.49), epidermal growth factor receptor/erythroblastosis oncogene B (c-erb) (HR, 2.59), and retinoblastoma protein loss (HR, 1.85); DFS was associated with cyclin D1 (HR, 2.16) and highmolecular-weight cytokeratin (HR, 0.42); OS was associated with E-cadherin (HR, 0.34) and programmed cell death 1 ligand (HR, 13.42) (p < 0.05). Conclusion Several significant tissue markers were associated with survival outcomes in upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy.

The Prevalence and Prognostic Role of PD-L1 in Upper Tract Urothelial Carcinoma Patients Underwent Radical Nephroureterectomy: A Systematic Review and Meta-Analysis

“…All the studies adopted immunohistochemistry (IHC) to analyze the level of PD-L1 in tumor tissues. Notably, the intensity of PD-L1 in IHC was only mentioned in four studies (14,(23)(24)(25), while none of them reported neither the mean/median intensity nor its linear correlation with the outcomes. The NOS grades indicated that all studies had high qualities (Supplementary Table 2).…”

“…We excluded records for the following reasons: article types or not relevant topics (n = 188), studies had few study samples (≤50) or follow-up duration less than 12 months (n = 4), not in English (n = 9), or insufficient survival data (n = 15). Finally, we included eight retrospective cohort studies (1,406 individuals) (13)(14)(15)(16)(17)(23)(24)(25) in the study (shown in Figure 1).…”

“…In recent years, studies have increased dramatically in investigating the association between PD-L1 and survival outcomes in radically resected UTUC patients and the conclusion is still controversial. Some evidence indicated that higher PD-L1 was related to poor survival for UTUC ( 13 , 14 ), while some reported opposing findings ( 15 – 17 ). Therefore, we formulated clinical questions following the PICOS strategy and firstly assessed whether PD-L1 expression (high or low) was related to survival outcomes or the clinicopathological features in UTUC patients after RNU with no restriction to the study designs through a meta-analysis.…”

A multi‐institutional retrospective study of open versus laparoscopic nephroureterectomy focused on the intravesical recurrence

“…[27][28][29] In addition, several molecular proteins have not only been investigated for their potential as prognostic factors but are also associated with IVR in patients with UTUC, showing the relevance of molecular biology findings in clinical practice. 30 Huang et al 31 suggested that the high expression of amplified in breast cancer 1, a human oncogene, is involved in a number of biological processes, such as cell proliferation, cell migration, and cell differentiation. In addition, eukaryotic initiation factor 5A2, which is also classified as an oncogene and an independent molecular marker for shorter survival time in patients with bladder cancer treated with radical cystectomy, is a risk factor for IVR.…”

“…Recently, postoperative single‐dose intravesical chemotherapy after nephroureterectomy has been recommended, as it significantly reduces the likelihood of IVR 27–29 . In addition, several molecular proteins have not only been investigated for their potential as prognostic factors but are also associated with IVR in patients with UTUC, showing the relevance of molecular biology findings in clinical practice 30 . Huang et al 31 .…”