scholarly journals Assessment of HER2 Expression in Canine Urothelial Carcinoma of the Urinary Bladder

2019 ◽  
Vol 56 (3) ◽  
pp. 369-376 ◽  
Author(s):  
Masaya Tsuboi ◽  
Kosei Sakai ◽  
Shingo Maeda ◽  
James K. Chambers ◽  
Tomohiro Yonezawa ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Urothelial Carcinoma ◽  
Evaluation Method ◽  
Growth Factor Receptor ◽  
Her2 Expression ◽  
Clinical Factors ◽  
Normal Bladder ◽  
Cell Proliferation And Differentiation ◽  
Polypoid Cystitis ◽  
Her2 Positivity

Canine urothelial carcinoma (UC) has a poor prognosis and high metastatic rate. Human epidermal growth factor receptor 2 (HER2), a receptor tyrosine kinase involved in cell proliferation and differentiation regulation, has been attracting interest as a therapeutic target molecule for human breast cancer. This study investigated expression of the canine homolog of HER2 (ERBB2) in canine UC, and its association with clinical factors. Since it has been controversial whether commercial anti-human HER2 antibody (Dako A0485) correctly recognizes the canine homolog of HER2, an application of the antibody using a canine UC cell line was validated first. By Western blot, a single band at the appropriate size for canine HER2 (185 kDa) was recognized. Immunohistochemistry for HER2 was performed on 23 samples of UC, 8 samples of polypoid cystitis, and 8 samples of normal urinary bladder, and the results were scored as either 0, 1+, 2+, or 3+ with reference to the evaluation method for human UC. Intense membranous HER2 immunoreactivity was frequently observed in neoplastic cells, especially in grade 2 UC. Minor HER2 expression was found in the epithelial cells of polypoid cystitis and normal bladder. The incidence of HER2 positivity (scores of 2+ or 3+) was 14 of 23 (60.9%) in UC, 3 of 8 (37.5%) in polypoid cystitis, and 0 of 8 (0%) in normal bladder. There was no significant correlation between HER2 positivity and clinical factors. While increased HER2 expression was observed in a subset of urothelial carcinomas, further mechanistic studies are needed to determine its role in the pathogenesis and targeted therapy of this cancer.

scholarly journals ErbB2 Copy Number Aberration in Canine Urothelial Carcinoma Detected by a Digital Polymerase Chain Reaction Assay

2019 ◽  
Vol 57 (1) ◽  
pp. 56-65 ◽  
Author(s):  
Kosei Sakai ◽  
Shingo Maeda ◽  
Kohei Saeki ◽  
Ryohei Yoshitake ◽  
Yuko Goto-Koshino ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Urothelial Carcinoma ◽  
Copy Number ◽  
Digital Pcr ◽  
Copy Number Aberration ◽  
Chromosome 8 ◽  
Pcr Assay ◽  
Formalin Fixed Paraffin Embedded ◽  
Polypoid Cystitis ◽  
Normal Controls

Urothelial carcinoma (UC) is the most common tumor affecting the urinary bladder of dogs. Protein overexpression of ErbB2 (the canine homolog of HER2) has been observed in dogs with UC. However, no study regarding ErbB2 copy number aberration (CNA) is reported in dogs with UC. In this study, a digital PCR assay for detecting CNA of canine ErbB2 was developed. DNA samples were isolated from 83 formalin-fixed, paraffin-embedded urinary bladder tissues (36 UC, 8 polypoid cystitis, and 39 normal) and 94 urinary sediments (54 UC, 30 nonneoplastic, and 10 normal). The copy number of canine chromosome 8 ( CFA8) was used as a control. In the urinary bladder tissues, ErbB2 CNA was detected in 12 of 36 (33%) UC, 2 of 8 (25%) polypoid cystitis, and 0 of 39 (0%) normal controls. In the urinary sediments, ErbB2 CNA was also detected in 19 of 54 (35%) UC; however, no ErbB2 CNA was detected in nonneoplastic diseases or normal controls. The sensitivity and specificity of ErbB2 CNA in urinary sediment for the detection of UC were 35% and 100%, respectively. There was a positive correlation between the copy number ratios of ErbB2 to CFA8 in the urinary bladder tissues and urinary sediments. Our findings indicate that the digital PCR assay of urinary sediments may be a useful, noninvasive method for detecting ErbB2 CNA in dogs with UC.

scholarly journals SALL4 Expression in Urothelial Carcinoma of Urinary Bladder; a Tissue Microarray Analysis

2020 ◽  
pp. 1-3
Author(s):  
Jaudah Al-Maghrabi ◽  
◽  
Haneen Al-Maghrabi ◽  
Ahmad Ghanim ◽  
Ayman Ghanim ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Germ Cell ◽  
Urothelial Carcinoma ◽  
Regional Lymph Node ◽  
Germ Cell Tumors ◽  
Unknown Origin ◽  
High Grade ◽  
Urothelial Carcinomas ◽  
Normal Bladder ◽  
Bladder Urothelial Carcinoma

Sal-like protein 4 (SALL4) is a cellular pluripotent embryonic nuclear factor that has been a useful immunohistochemistry marker for germ-cell tumors. Our understanding of SALL4 expression in other human body malignancies remains limited. The diagnostic value of SALL4 expression as an independent diagnostic marker for patients with bladder urothelial carcinoma remains unclear. The aim of this study is to investigate the relation of SALL4 immunostaining in urinary bladder urothelial carcinoma and normal bladder urothelial tissue with clinicopathological diagnostic parameters. Material and methods: Three hundred and seventy cases of bladder urothelial carcinomas and 22 non-neoplastic bladder urothelial tissues were obtained from the Department of Pathology at King Abdulaziz University Jeddah, Saudi Arabia. Tissue microarrays were constructed. Tissue sections were stained using anti-human SALL4 monoclonal antibody. The immunostaining results were recorded and analyzed. Results: SALL4 exhibited weak nuclear expression in only 6 out of 370 cases of bladder urothelial carcinomas (1.6%). All the SALL4-positive cases were high-grade tumors. Normal urothelial tissues were all completely negative. SALL4 immunostaining revealed no association with gender, age, tumor invasiveness, stage, lymphovascular invasion, regional lymph node metastasis, or distant metastasis. Conclusion: SALL4 is rarely expressed in bladder urothelial carcinoma and is typically limited to high-grade tumors. However, this immunoexpression must be kept in mind when applying SALL4 antibody for differentiating urothelial carcinomas from germ-cell tumors and when assessing metastatic poorly differentiated tumors of unknown origin.

HER2 Expression in Gastric Cancer and Gastroesophageal Junction Cancer

2020 ◽  
Vol 22 (2) ◽  
pp. 79-82
Author(s):  
Md Azizur Rahman ◽  
Abdullah Md Abu Ayub Ansari ◽  
Kazi Mazharul Islam ◽  
Md Aminur Rahman ◽  
ABM Abdul Matin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Social Impact ◽  
Gastroesophageal Junction ◽  
Treatment Protocol ◽  
Armed Forces ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Cancer Data ◽  
Her2 Positivity

Background: Carcinoma of the stomach is a major cause of cancer mortality worldwide. Due to social impact of gastric carcinoma (GC), there is a need to stratify patients into appropriate screening, surveillance and treatment programs. Although histopathology remains the most reliable and less expensive method, numerous efforts have been made to identify and validate novel biomarkers to accomplish the goals. In recent years, several molecules have been identified and tested for their clinical relevace in GC management. Among the biomarkers with the exception of HER2, none of the biomarkers is currently used in clinical practice, and some of them were described in single studies. Materials and Methods: This prospective type of observational study was performed in the Department of Surgery, Dhaka Medical College Hospital, Dhaka, 6 months from approval of protocol. Total 45 consecutive patients aged 18 years and above without consideration of gender were selected purposefully. Every patient was evaluated by clinical examination, appropriate investigations and after a confirm diagnosis of the tissue from the cancer. All patients have undergone operative intervention and Gastrectomy specimens were subtotal (including cardiac and pylorus), subtotal (including the pylorus), total radical gastrectomy and oesophago-gastrectomy sample. All specimens obtained were immersed in 10% formalin. Samples of whom were sent to the department of pathology, DMCH for histopathology examination. Portion of representative tissue/block was sent to AFIP (Armed Forces Institute of Pathology, Dhaka) for immunohistochemistry to find out the HER2 expression in gastric cancer and gastro-oesophageal cancer. Data was collected in a pre-designed questionnaire by face to face interview. Result and observation: In this study when 45 cases were categorized according to WHO grading system it was observed that majority (30) patients were found in grade II, among them 3(10%) were HER2 positive. But with grade III tumour the HER2 positivity were found more i,e; 37.5% (3/8). Grade- I tumor show HER2 neu expression 28.57% (2/7) and according to location most of the cases with HER2 positive expression was located in the gastro-esophageal junction which is 27.27% (3/11) than gastric carcinoma which is 14.70% (5/34). Conclusion: Most of the patients of gastric and gastrooesophageal junction adenocarcinoma are diagnosed at a very late stage, so they require special attention in treatment protocol, including chemotherapy and immunotherapy for increasing their survivability. The study showed with poorly differentiated (high grade) tumour, the HER2 positivity were found more. Journal of Surgical Sciences (2018) Vol. 22 (2) : 79-82

Fibroblast Growth Factor Receptor Inhibitor–Associated Multifocal Serous Retinal Detachments: A Case Report

2021 ◽  
pp. 247412642110136
Author(s):  
Diana H. Kim ◽  
Tian Xia ◽  
Peter Bracha ◽  
Brian L. VanderBeek
Keyword(s):  
Case Report ◽  
Growth Factor ◽  
Urothelial Carcinoma ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Metastatic Urothelial Carcinoma ◽  
Optical Coherence Tomography Imaging ◽  
Receptor Inhibitor

Purpose: This report aims to describe a case of bilateral, multifocal neurosensory retinal detachments that developed during erdafitinib therapy for metastatic urothelial carcinoma. Methods: A case report with color fundus imaging and spectral-domain optical coherence tomography imaging is presented. Results: A 50-year-old man with metastatic urothelial carcinoma had an unremarkable baseline ophthalmic examination prior to starting erdafitinib. At 3-month follow up, an examination revealed bilateral, multifocal retinal detachments. Because the patient was asymptomatic and erdafitinib was the only drug to which his tumor had responded, he was kept on the medication with close ophthalmic monitoring. Conclusions: Erdafitinib, a fibroblast growth factor receptor inhibitor, can cause bilateral, multifocal retinal detachments. Continuation of erdafitinib may be considered in patients without significant visual impairment when the overall benefit of the medication appears to outweigh the risks.

scholarly journals Expression of Semaphorin 3A in Malignant and Normal Bladder Tissue: Immunohistochemistry Staining and Morphometric Evaluation

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 109
Author(s):  
Ilan Bejar ◽  
Jacob Rubinstein ◽  
Jacob Bejar ◽  
Edmond Sabo ◽  
Hilla K Sheffer ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Carcinoma In Situ ◽  
Urothelial Cancer ◽  
Basal Layer ◽  
Low Grade ◽  
High Grade ◽  
Bladder Tissue ◽  
Normal Bladder ◽  
Normal Bladder Tissue

Introduction: Our previous studies showed elevated levels of Semaphorin3a (Sema3A) in the urine of patients with urothelial cancer compared to healthy patients. The aim of this study was to analyze the extent of Sema3A expression in normal and malignant urothelial tissue using immune-staining microscopic and morphometric analysis. Materials and Methods: Fifty-seven paraffin-embedded bladder samples were retrieved from our pathology archive and analyzed: 14 samples of normal urothelium, 21 samples containing low-grade urothelial carcinoma, 13 samples of patients with high-grade urothelial carcinoma, 7 samples containing muscle invasive urothelial carcinoma, and 2 samples with pure urothelial carcinoma in situ. All samples were immunostained with anti Sema3A antibodies. The area of tissue stained with Sema3A and its intensity were analyzed using computerized morphometry and compared between the samples’ groups. Results: In normal bladder tissue, very light Sema3A staining was demonstrated on the mucosal basal layer and completely disappeared on the apical layer. In low-grade tumor samples, cells in the basal layer of the mucosa were also lightly stained with Sema3A, but Seama3A expression intensified upon moving apically, reaching its highest level on apical cells exfoliating to the urine. In high grade urothelial tumors, Seama3A staining was intense in the entire thickness of the mucosa. In samples containing carcinoma in situ, staining intensity was high and homogenous in all the neoplastic cells. Conclusions: Sema3A may be serve as a potential non-invasive marker of urothelial cancer.

scholarly journals The Prognostic Impact of HER2 Genetic and Protein Expression in Pancreatic Carcinoma—HER2 Protein and Gene in Pancreatic Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 653
Author(s):  
Song-Hee Han ◽  
Ki Hyun Ryu ◽  
Ah-Young Kwon
Keyword(s):  
Protein Expression ◽  
Genetic Heterogeneity ◽  
Growth Factor Receptor ◽  
Ductal Adenocarcinoma ◽  
Prognostic Impact ◽  
Her2 Expression ◽  
Her2 Protein ◽  
Epidermal Growth ◽  
Her2 Heterogeneity

Pancreatic ductal adenocarcinoma (PDAC) is a lethal and clinically heterogeneous disease with a limited benefit from human epidermal growth factor receptor 2 (HER2)-targeted therapy. Recently, some studies have addressed the antitumoral effect of novel anti-HER2 drugs in HER2 low-expressing tumors. However, there have been few studies on the significance of low HER2 expression and genetic heterogeneity in PDAC. Using immunohistochemistry and dual-color silver-enhanced in situ hybridization based on the Trastuzumab for a gastric cancer scoring scheme, we evaluated HER2 protein expression, gene amplification, and genetic heterogeneity in three groups (HER2-neg, HER2-low, HER2-pos) of 55 patients. Among the 55 cases, 41.8% (23/55) showed HER2 expression of any intensity. HER2 amplification independent of HER2 expression was 25.5% (14/55). Patients in both these groups had a shorter overall survival than did patients in the HER2-neg group. HER2 genetic heterogeneity was identified in 37 (70.9%) of the 55 cases, mainly in HER2-neg and HER2-low groups. HER2 genetic heterogeneity significantly correlated with worse survival in the HER2-low and HER2-neg groups of PDAC. These findings support the hypothesis that low-level HER2 expression and heterogeneity have significant clinical implications in PDAC. HER2 heterogeneity might indicate the best strategies of combination therapies to prevent the development of subdominant clones with resistance potential.

Sign in / Sign up

Export Citation Format

Share Document