WHO 1973 grade 3 and infiltrative growth pattern proved, aberrant E-cadherin expression tends to be of predictive value for progression in a series of stage T1 high-grade bladder cancer after organ-sparing approach

Otto, Wolfgang; Breyer, Johannes; Herdegen, Sonja; Eder, Fabian; Bertz, Simone; May, Matthias; Mayr, Roman; Lausenmeyer, Eva Maria; Denzinger, Stefan; Burger, Maximilian; Hartmann, Arndt

doi:10.1007/s11255-016-1491-9

Cited by 16 publications

(10 citation statements)

References 29 publications

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“…However, the role of E-cadherin in the prognosis of BC remains controversial. Many studies have shown that reduced E-cadherin expression is associated with poor prognosis for BC patients [ 12 – 16 ], but some studies have suggested that there is no relationship between E-cadherin expression and prognosis in BC patients [ 17 – 20 ]. Moreover, numerous studies published in this field are small in size.…”

Section: Introductionmentioning

confidence: 99%

Reduced E-cadherin expression is correlated with poor prognosis in patients with bladder cancer: a systematic review and meta-analysis

et al. 2017

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The prognostic significance of E-cadherin expression in bladder cancer (BC) has been elevated for years, but published results remain controversial and inconsistent. We thus performed a systematic review and meta-analysis to determine the association between E-cadherin expression and BC prognosis. We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases to identify eligible studies published until March 2017. On the basis of our inclusion and exclusion criteria, a total of 2,089 patients from 19 studies were eligible for final analysis. Our results showed that reduced E-cadherin expression in BC was associated with poor overall survival (hazard ratio [HR] = 2.73, 95% CI: 1.74–4.27, p < 0.001), poor progression-free survival (HR = 6.39, 95% CI: 3.48–11.73, p < 0.001), and poor recurrence-free survival (HR = 2.48, 95% CI: 1.68–3.64, p < 0.001). Moreover, reduced E-cadherin expression was significantly correlated with pathological T stage (T2-4 vs. Ta-1: risk ratio [RR] = 2.14, 95% CI: 1.70–2.71), metastasis (yes vs. no: RR = 1.68, 95% CI: 1.17–2.40), grade (3 vs. 1/2: RR = 1.58, 95% CI: 1.29–1.93), and carcinoma in situ (yes vs. no: RR = 1.68, 95% CI: 1.09–2.58). This meta-analysis suggested that reduced E-cadherin expression was associated with poor prognosis and advanced clinicopathological characteristics and can serve as a useful biomarker for the clinical management of BC.

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Section: Introductionmentioning

confidence: 99%

Reduced E-cadherin expression is correlated with poor prognosis in patients with bladder cancer: a systematic review and meta-analysis

et al. 2017

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“…Positive control slides were also stained in the same run (normal urothelium was used as positive control for E-cadherin and intraductal carcinoma of breast tissues was used as positive control for HER2/neu). E-cadherin was evaluated as follows [18]: Uniformly positive (+): More than 90% of tumor cells are stained (membranous), heterogeneous (±): More than 10 and <90% of the tumor cells are positive (membranous and cytoplasmic), and negative: <10% of the tumor cells were positive.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Correlation of Muscle Invasion in Bladder Cancer with Cell Adhesion Properties and Oncoprotein Overexpression Using E-Cadherin and HER2/neu Immunohistochemical Markers.

Esmail¹,

Abdellah²,

Abdel‐Salam³

2020

Open Access Maced J Med Sci

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BACKGROUND: Most of bladder cancers are proven to be of urothelial origin (transitional cell carcinomas). Above 75% of them are of non-muscle invasive bladder cancer (NMIBC) type at presentation and the remainder are MIBC. Recent studies suggest that both are most probably two different categories based on both the histopathological and molecular features. The comprehensive understanding of the biomarkers expression in both categories will help in understanding the molecular event underlying each of them and may provide possible chances for targeted therapeutic options. AIM: This study aims to study the differential expression of both E-cadherin and human epidermal growth factor receptor-2 (HER2) in the two categories of bladder cancer NMIBCs and MIBCs. MATERIALS AND METHODS: A total of 40 blocks were collected retrospectively from cases of cancer bladder, segregated as 20 cases NMIBCs and 20 cases MIBCs, subjected for E-cadherin and HER2 immunostaining. RESULTS: E-cadherin showed positive expression in 65% of cases of NMI group and in 10% of the MI group, with high statistical significance (p < 0.001). Regarding HER2, positive expression was seen in 25% of NMI cases and in 90% of MI cases, with statistical significance (p < 0.001). Comparison of the results of both markers and their correlation per case showed that 90% of tumors with muscle invasion were E-cadherin negative and HER2 positive. CONCLUSION: The significant association of loss of E-cadherin immunohistochemistry expression and positive HER2 overexpression in MIBC versus NMIBC figured out more differences between the two categories and added to the understanding of their biology. The possibility of validation of HER2-targeted therapy in MIBC cases is now strongly suggested.

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“…Other studies had shown associations between EMT marker expression in bladder cancer and survival [37–39]. Additionally, Otto et al [40] demonstrated that aberrant E‐cadherin expression was predictive of T1 progression. However, EMT is just one mechanism of tumour progression.…”

Section: Discussionmentioning

confidence: 99%

Greater utility of molecular subtype rather than epithelial‐to‐mesenchymal transition (EMT) markers for prognosis in high‐risk non‐muscle‐invasive (HGT1) bladder cancer

Ottley

Pell

Brazier

et al. 2020

The Journal of Pathology CR

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Approximately 75% of bladder cancers are non-muscle invasive (NMIBC). Of these, up to 53% of cases progress to life-threatening muscle-invasive bladder cancer (MIBC). Patients with high-grade stage T1 (HGT1) NMIBC frequently undergo radical cystectomy (RC), although this represents overtreatment for many. Identification of progressors versus non-progressors could spare unnecessary treatment. Recent studies have confirmed that urothelial carcinoma is composed of two main molecular subtypes, basal and luminal, with 12% of basal tumours exhibiting epithelial-to-mesenchymal transition (EMT). Levels of immune cell infiltration have been shown to be subtype-specific. Here, we performed immunohistochemistry (IHC) for 11 antibodies relating to molecular subtypes or EMT in 26 cases of HGT1 urothelial carcinoma cases with 6 matched samples subsequently obtained at cystectomy (n = 6; 1 muscle-invasive, 5 non-muscle-invasive; 3 = pTis, 1 = pT1, 1 = pTa) and at recurrence (n = 2, pT2). RNAScope was also conducted in a subset. Expression patterns in HGT1 specimens versus MIBC (pT2 +) were examined, and correlated with disease-specific survival (DSS). Levels of stromal tumour-infiltrating lymphocytes (sTILs) were assessed manually to determine whether lymphocyte infiltration was associated with DSS and whether differences existed between HGT1 and MIBC. Molecular subtype markers demonstrated increased prognostic potential compared to the EMT markers assessed. Increased expression of the luminal markers FOXA1 and SCUBE2, were found to be significantly associated with better DFS. No EMT markers were significantly associated with DFS. In areas of non-invasive papillary urothelial carcinoma, but not invasive carcinoma, sTIL levels were found to be significantly associated with DFS. While differences were observed between HGT1 cases that progressed versus those that did not, a larger cohort study is required for validation of these findings. Taken together, an emphasis on molecular subtype markers, rather than EMT markers, may be preferable when studying biomarkers of HGT1 urothelial carcinoma in the future.

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WHO 1973 grade 3 and infiltrative growth pattern proved, aberrant E-cadherin expression tends to be of predictive value for progression in a series of stage T1 high-grade bladder cancer after organ-sparing approach

Cited by 16 publications

References 29 publications

Reduced E-cadherin expression is correlated with poor prognosis in patients with bladder cancer: a systematic review and meta-analysis

Reduced E-cadherin expression is correlated with poor prognosis in patients with bladder cancer: a systematic review and meta-analysis

Correlation of Muscle Invasion in Bladder Cancer with Cell Adhesion Properties and Oncoprotein Overexpression Using E-Cadherin and HER2/neu Immunohistochemical Markers.

Greater utility of molecular subtype rather than epithelial‐to‐mesenchymal transition (EMT) markers for prognosis in high‐risk non‐muscle‐invasive (HGT1) bladder cancer

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