Prognostic role of decreased E-cadherin expression in patients with upper tract urothelial carcinoma: a multi-institutional study

Abstract

Purpose To assess the role of E-cadherin as prognostic biomarker in upper tract urothelial carcinoma (UTUC) in a large multi-institutional cohort of patients.Methods Immunohistochemistry technique was used to evaluate E-cadherin expression in 678 patients with unilateral, sporadic UTUC treated with RNU. E-cadherin expression was considered decreased if 10 % or more cells had decreased expression (<90 %).ResultsDecreased E-cadherin expression was observed in 353 patients (52.1 %) and was associated with advanced pathological stage (P < 0.001), higher grade (P < 0.001), lymph node metastasis (P = 0.006), lymphovascular invasion (P < 0.001), concomitant carcinoma in situ (P < 0.001), multifocality (P = 0.004), tumor necrosis (P = 0.020) and sessile architecture (P < 0.001). Within a median follow-up of 30 months (interquartile range 15–57), 171 patients (25.4 %) experienced disease recurrence and 150 (21.9 %) died from UTUC. In univariable analyses, decreased E-cadherin expression was significantly associated with worse recurrence-free survival (P < 0.001) and cancer-specific survival CSS (P = 0.006); however, in multivariable analyses, it was not (P = 0.74 and 0.84, respectively). The lack of independent prognostic value of E-cadherin remained true in all subgroup analyses.ConclusionIn UTUC patients treated with RNU, decreased E-cadherin expression is associated with features of biologically and clinically aggressive disease and worse outcome in univariable, but not multivariable, analyses. If E-cadherin’s association with factors of advanced disease is confirmed on UTUC biopsy specimens, it could be used to help in the clinical decision-making regarding kidney-sparing approaches and/or neo-adjuvant chemotherapy.

Impact of tumor architecture on disease recurrence and cancer-specific mortality of upper tract urothelial carcinoma treated with radical nephroureterectomy

“…Through extensive research, a total of 18 articles, including 17 published articles and our retrospective study, were included in the meta-analysis. 7,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] It is pointed out that although some of articles 6,10,16 selected in their meta-analysis came Patients with sessile tumor architecture exhibited a significantly lower RFS (p = 0.001, log-rank test) and CSS (p = 0.009, log-rank test) rate than patients with papillary tumor architecture. from multi-institutional collaborative database organized by Shariat, they were characterized by different origin of dataset or recruitment period, so included them as different studies in our analysis.…”

“…They were published from 2009 10 to 2016. 15 The sample size ranged from 101 to 2477 13 patients, and the mean/median follow-up durations varied from 27 11 to 47.5 7 months. Figure 4(a) shows the pooled results from the random effects model combining the HRs for disease recurrence after surgery.…”

“…12,14 The prognostic value of potentially important features, such as tumor architecture, remains to be proven. 12,14,15 Several studies have reported that macroscopic sessile tumor architecture is independently associated with adverse outcomes after RNU for UTUC in large multiinstitutional retrospective studies. 7,13,16 Since proof attesting its current role in UTUC is relatively poor and few studies on macroscopic tumor architecture in UTUC of Chinese mainland patients are available, it is of utmost importance to combine these data to reach a reasonable conclusion.…”

Tissue-based molecular markers in upper tract urothelial carcinoma and their prognostic implications

“…In contrast, most subsequent studies of larger cohorts have failed to demonstrate an independent association between E-cadherin expression and disease recurrence ( 58 , 59 ). Favaretto et al assessed the clinical significance of lower E-cadherin levels in an international cohort of 678 UTUC patients who were treated with RNU ( 60 ), observing that downregulation of E-cadherin in tumor cells correlated with adverse clinicopathological features. They also confirmed that lower E-cadherin expression was linked to a greater probability of disease recurrence and cancer-specific mortality in UTUC.…”

LncRNA HOTAIR regulates the expression of E-cadherin to affect nasopharyngeal carcinoma progression by recruiting histone methylase EZH2 to mediate H3K27 trimethylation

“…About the enhancer of zeste homolog 2 (EZH2), which is a contributor to cell cycle regulation and tumorigenesis, is enhanced in NPC; and ectopic EZH2 overexpression is able to induce invasion of NPC cells, and E-cadherin is reduced [9]. Concerning to E-cadherin, it is concluded that decreased expression of E-cadherin has been established as a feature of epithelial-mesenchymal transition in epithelial malignancies [10]. The trimethylation of lysine 27 on histone H3 (H3K27me3), a transcriptional inhibitory histone modification involving tumorigenesis is methylated by EZH2 [11].…”