Different HER2 Protein Expression Profiles Aid in the Histologic Differential Diagnosis Between Urothelial Carcinoma In Situ (CIS) and Non-CIS Conditions (Dysplasia and Reactive Atypia) of the Urinary Bladder Mucosa

Gunia, Sven; Koch, Stefan; Hakenberg, Oliver W.; May, Matthias; Kakies, Christoph; Erbersdobler, Andreas

doi:10.1309/ajcpkuz69lxzgfea

Cited by 18 publications

(11 citation statements)

References 26 publications

(28 reference statements)

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“…The association between HER2 overexpression and grade is confirmed by its detection in bladder CIS with high sensitivity and specificity compared to benign/reactive urothelium to the extent that it can be considered a reliable diagnostic marker in this setting [80][81][82].…”

Section: Association Of Clinical and Pathological Parameters With Hermentioning

confidence: 85%

Human Epidermal Growth Factor Receptor 2 in Non-Muscle Invasive Bladder Cancer: Issues in Assessment Methods and Its Role as Prognostic/Predictive Marker and Putative Therapeutic Target: A Comprehensive Review

et al. 2018

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Although human epidermal growth factor receptor 2 (HER2) plays a prognostic and predictive role in breast and gastric cancer, its function in bladder cancer (BC) is still controversial. A comprehensive review of the literature has been carried out. An electronic search of databases from PubMed, Scopus, Google Scholar was implemented. The search terms were: “BC,” “bladder carcinoma,” “bladder neoplasm,” “human epidermal growth factor 2,” “HER2,” “HER-2,” “c-erbB-2,” “c-erbB2,” “erbB-2,” “erbB2,” “neu,” “marker,” “biomarker,” and “prognosis”. Results of the review consented to (a) summarize the available data on HER2 a predictor of recurrence and/or progression free survival on univariate and multivariate analysis, (b) explore the related issues in assessing HER2 status on these tumor samples, since they may severely impair its predictive function, and (c) report the state-of-the art of HER2 as a putative therapeutic target in BC and especially non-muscle invasive BC. HER2 stands out for being a prognostic factor as well as a therapeutic target in various cancers. Data from the literature concerning its use in BC provide conflicting results, probably due to the inherent complexity of BC biology. Efforts should be made to establish a suitable tumor-specific scoring system, and to assess single drugs’ efficacy in well-designed clinical trials.

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Section: Association Of Clinical and Pathological Parameters With Hermentioning

confidence: 85%

Human Epidermal Growth Factor Receptor 2 in Non-Muscle Invasive Bladder Cancer: Issues in Assessment Methods and Its Role as Prognostic/Predictive Marker and Putative Therapeutic Target: A Comprehensive Review

et al. 2018

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“…Tumor samples on TMAs in triplicate were analyzed for HER2 expression. For all cases, the assessment of HER2 was performed using the 2010 USCO/CAP HER2 guidelines as established for breast cancer , which has been previously employed to assess HER2 expression in bladder cancer . HER2 staining and its categorization based on localization and intensity is depicted in Figure A.…”

Section: Methodsmentioning

confidence: 99%

HER2 as a target in invasive urothelial carcinoma

et al. 2015

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We evaluated primary tumors from two cohorts, Spain (N = 111) and Greece (N = 102), for patients who were treated with platinum-based chemotherapy. Patients were tested for HER2 status (IHC score of 3+ or FISH ratio of ≥2.2) by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), DNA copy number, mRNA expression, and mutation status in patients with metastatic urothelial carcinoma (UC), and its impact on survival. ERBB2 mutation was determined by hotspot sequencing. mRNA expression was assessed using NanoString counting. Association of overall survival (OS) and HER2 status was assessed by a Cox regression model. NIH-3T3 cells containing HER2 V777L were assessed for growth, invasion, and HER2 kinase activation. In all, 22% of Spanish and 4% of Greek cohorts had 3+ HER2 staining by IHC. FISH amplification was identified in 20% of Spanish and 4% of Greek cohorts. Kappa coefficient between FISH and IHC was 0.47. HER2 status was not associated with OS in univariate (Spanish P = 0.34; Greek P = 0.11) or multivariate (Spanish P = 0.49; Greek P = 0.12) analysis. HER2-positive tumors expressed higher levels of HER2 mRNA than HER2-negative tumors (P < 0.001). HER2 mutations (V777L and L755S) were identified in two (2%) patients. In vitro analysis of V777L results in transformation of NIH-3T3 cells, leading to increased growth, invasion on soft agar, and HER2 kinase constitutive activation. In summary, HER2 overexpression or amplification in the primary tumor did not predict OS in patients with metastatic UC. HER2 positivity rates can differ between different populations. Further trials in genomically screened patients are needed to assess HER2-targeted therapies in UC.

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“…Little is known about the expression of ERBB2 in Cis of the bladder. Gunia et al [18] could show a strong expression of HER2 in Cis, whereas the non-Cis tissue showed a weak to absent HER2 expression in immunohistochemical staining. Sjödahl et al [12] could not find an association between ERBB2 expression and the stage and grade of bladder cancer.…”

Section: Discussionmentioning

confidence: 92%

ERBB2 Expression as Potential Risk-Stratification for Early Cystectomy in Patients with pT1 Bladder Cancer and Concomitant Carcinoma in situ

Breyer

Otto²,

Wirtz³

et al. 2016

Urol Int

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Background/Aims/Objectives: It is difficult to identify patients with a non-muscle-invasive bladder cancer (NMIBC) at stage pT1 with concomitant carcinoma in situ (Cis) who will benefit from an early cystectomy. Methods: We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues of patients with NMIBC. Messenger ribonucleic acid (mRNA) expression of progesterone receptor (PGR), estrogen receptor (ESR1), ERBB2, and marker of proliferation Ki-67 (MKI67) was measured by single-step reverse transcription quantitative real-time polymerase chain reaction using RNA-specific TaqMan assays. Relative gene expression was determined by the normalization of 2 reference genes (CALM2, B2M) using the 40 ΔΔCT method and relative gene expression was correlated to the histopathological stage and oncological outcome. Results: Of 302 patients with pT1 NMIBC in the initial transurethral resection of the bladder, 65 had a concomitant Cis. Elevated ERBB2 expression (>40.1) significantly correlated with progress in patients with and without concomitant Cis (p = 0.020 and p = 0.049, respectively). For the subgroup of pT1 with concomitant Cis, elevated ERBB2 expression significantly discriminated between a high-risk group of 55% progression-free survival (PFS) and a low-risk group of 90% PFS after a 5-year follow-up (p = 0.020). Cox-regression analysis revealed ERBB2 expression as the only independent prognostic factor for PFS (p = 0.0037). Conclusions: High mRNA expression of ERBB2 can identify patients with pT1 NMIBC with concomitant Cis, who have a high risk of progression and might benefit from an early cystectomy.

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Different HER2 Protein Expression Profiles Aid in the Histologic Differential Diagnosis Between Urothelial Carcinoma In Situ (CIS) and Non-CIS Conditions (Dysplasia and Reactive Atypia) of the Urinary Bladder Mucosa

Cited by 18 publications

References 26 publications

Human Epidermal Growth Factor Receptor 2 in Non-Muscle Invasive Bladder Cancer: Issues in Assessment Methods and Its Role as Prognostic/Predictive Marker and Putative Therapeutic Target: A Comprehensive Review

Human Epidermal Growth Factor Receptor 2 in Non-Muscle Invasive Bladder Cancer: Issues in Assessment Methods and Its Role as Prognostic/Predictive Marker and Putative Therapeutic Target: A Comprehensive Review

HER2 as a target in invasive urothelial carcinoma

ERBB2 Expression as Potential Risk-Stratification for Early Cystectomy in Patients with pT1 Bladder Cancer and Concomitant Carcinoma in situ

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