The clinical significance of HER2 protein amplification/expression in urinary bladder lesion

Hammam, Olfat; Nour, Hani H.; Mosaad, Maha; Akl, Maha; Khalil, Heba; Ganzory, Hossam al; Hindawi, Ali El

doi:10.1016/j.aju.2015.01.004

Cited by 12 publications

(10 citation statements)

References 23 publications

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“…The expression in the positive cases was diffuse (70-100% of tumor cells). These results agree with Hammam et al, 2015, study [26], which showed equivocal Her2 expression (score 2, which is considered negative in their study) in 23% of NMIBC cases and positive (score 3) expression in 43% and 46% of T1 and T2-3 tumors, respectively, with statistical significance. Kolla et al, 2008 [19], showed positive expression in more than 70% of the MIBC cases and suggested that HER2 expression might provide an additional significant prognostic information for patients with bladder cancer.…”

Section: Discussionsupporting

confidence: 92%

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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Section: Discussionsupporting

confidence: 92%

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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“…Increased amplification of Her2/neu was more common in higher histological grades than lower ones in several cancers including breast, bladder and osteosarcoma [ 33 – 35 ]. Similar correlations between Her2/neu status with high-grade and advanced stages (III/IV) were also reported in bladder cancer supporting more aggressive and proliferative diseases with these patients [ 36 ].…”

Section: Discussionsupporting

confidence: 77%

“…Despite some discrepancies regarding the level of concordance between IHC and FISH methods [ 37 – 39 ], so often both techniques consolidate each other and generate similar results [ 27 , 40 , 41 ]. Despite that IHC is more cost-effective and recommended by some studies [ 42 ], it has been reported that assessing Her2/neu gene amplification using in situ hybridization technique is a more reliable and accurate method to evaluate Her2/neu status in breast cancer patients [ 36 , 43 ]. Here we report that Her2/neu is amplified in 25 % of the analyzed cohort which is in line with IHC data.…”

Section: Discussionmentioning

confidence: 99%

“…However, patients with non-amplified Her2/neu gene were associated with prolonged DSS suggesting Her2/neu as an independent prognosticator of overall survival in bladder cancer ( p = 0.02). This association was previously examined in many cancer types [ 12 , 36 , 47 , 48 ]. The enhancement of cancer cell proliferation, motility, invasion and metastasis are possible factors that support such poor prognostic impact of Her2/neu on the overall survival in bladder cancer patients [ 49 – 51 ].…”

Section: Discussionmentioning

confidence: 99%

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Prognostic value of HER2 status in bladder transitional cell carcinoma revealed by both IHC and BDISH techniques

et al. 2016

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BackgroundHer2/neu is an oncogene that plays an important role in the pathogenesis of many cancer types. In bladder carcinoma (BC), the clinical significance of Her2/neu status remains under-investigated and poorly linked to the patients’ clinic-pathological features and survival status. Thus, the current study was conducted to assess Her2/neu status in a cohort of patients’ in Saudi Arabia, and to explore its prognostic value in BC.MethodsA total of 160 consent patients of transitional cell carcinoma (TCC) of bladder were arranged on a tissue microarray (TMA) and stained by immunohistochemistry (IHC) and bright-field dual in situ hybridization (BDISH) methods. The intensity of Her2/neu protein receptor immunostaining was evaluated, correlated to Her2/neu gene amplification status in TCC and assessed for potential clinical value by correlation measures.ResultsIHC data demonstrated that Her2/neu protein is expressed in 60 % (2+ and 3+) of our TCC patient’s cohort from Saudi Arabia. Her2/neu gene amplification is detected in 25 % by BDISH. There was a strong association between Her2/neu protein levels and lymph node invasion (p = 0.04), tumor stage (p = 0.002), vascular invasion and borderline significance with distant metastasis (p = 0.07). Amplification of Her2/neu gene was associated with tumor grade (p = 0.03) and poor disease-specific survival (p = 0.02), in that, patients with non-amplified Her2/neu gene live longer. Interestingly, there was a reasonable concordance rate (71 %) between IHC and BDISH data in the analyzed cohort.ConclusionThe study showed that 25 % of our patients’ cohort has Her2/neu over-expression. This Her2/neu (over-expression/amplification) status was concordant using either IHC or BDISH and significantly associated with disease aggressiveness and poor outcome. These findings suggested a potential impact of anti-Her2 targeted therapy in the treatment of bladder cancer with amplified/overexpressed HER2 that needs further investigation.

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“…In a study comparing fourteen prognostic biomarkers for SCC, a panel of five markers, including COX-2, FGF-2, p53, Bax, and epidermal growth factor receptor (EGFR), was determined to best represent outcomes after RC [29] . Human epidermal growth factor receptor 2 (HER-2) oncoprotein expression was also recently identified to be higher in SCC tumours, suggesting that HER-2-positive tumours could benefit from targeted agents [30] . As variations in specific biomarker expression may be associated with differences in outcomes and/or patient responsiveness to therapies, these biomarkers may be utilised to guide the optimal treatment approach.…”

Section: Recent Findingsmentioning

confidence: 99%

Squamous cell carcinoma of the urinary bladder: Systematic review of clinical characteristics and therapeutic approaches

Martin

Carballido

Ahmed

et al. 2016

Arab Journal of Urology

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ObjectiveTo highlight the current understanding of the epidemiology, clinicopathological characteristics, and management of squamous cell carcinoma (SCC) of the bladder, as it accounts for 2–5% of bladder tumours, with a focus on non-bilharzial-associated SCC (NB-SCC). The standard treatment for bladder SCC remains radical cystectomy (RC). We present an updated clinical profile of bladder SCC and a review of NB-SCC therapeutic approaches, including RC, neoadjuvant and adjuvant treatments, radiotherapy, chemotherapy, and immunotherapy.MethodsUsing search terms relating to SCC, urinary bladder, and treatment modalities, we performed a search of the PubMed and Embase databases to identify NB-SCC treatment approaches and outcomes. Peer-reviewed English language reports from 1975 to present assessing SCC management were included. Two authors independently screened and extracted the data.ResultsOf the 806 articles screened, 10 met the pre-defined inclusion criteria. RC was performed in seven of the 10 studies. Although radiotherapy alone yielded poor outcomes, preoperative radiotherapy and RC were associated with improved survival. There is little evidence supporting the use of chemotherapy in NB-SCC, and its efficacy in relation to RC is not known.ConclusionBased on current literature, there is insufficient evidence to provide a treatment recommendation for NB-SCC. Whilst RC is the standard of care, the role of preoperative radiotherapy should be revisited and compared to RC alone. Additional studies incorporating multimodal approaches, contemporary radiation techniques, and systemic therapies are warranted. Immunotherapy as a treatment for bladder SCC has yet to be investigated.

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The clinical significance of HER2 protein amplification/expression in urinary bladder lesion

Cited by 12 publications

References 23 publications

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

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

Prognostic value of HER2 status in bladder transitional cell carcinoma revealed by both IHC and BDISH techniques

Squamous cell carcinoma of the urinary bladder: Systematic review of clinical characteristics and therapeutic approaches

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