HER2 and TOP2A Gene Amplification and Protein Expression in Upper Tract Urothelial Carcinomas

2017 ◽  
Vol 24 (3) ◽  
pp. 575-581 ◽  
Author(s):  
Klaus Aumayr ◽  
Tobias Klatte ◽  
Barbara Neudert ◽  
Peter Birner ◽  
Shahrokh Shariat ◽  
...  
2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Bohyun Kim ◽  
Gilhyang Kim ◽  
Boram Song ◽  
Cheol Lee ◽  
Jeong Hwan Park ◽  
...  

Aim. HER2 overexpression has been reported in a minority of urothelial carcinomas, but little is known about HER2 protein expression and gene alterations in plasmacytoid urothelial carcinoma, a rare and aggressive variant. The aim of this study was to clarify the HER2 status in plasmacytoid urothelial carcinomas.Methods. Six cases of plasmacytoid urothelial carcinoma were included, in which we evaluated HER2 protein expression by immunohistochemistry (IHC) andHER2gene amplification by fluorescencein situhybridization (FISH).Results. The patients’ ages ranged from 57 to 83 years (mean age, 71 years). Five patients were male and one was female. The ratio of the plasmacytoid component ranged from 30% to 100% (mean, 77%). HER2 expression score was 3+ in 4 cases, 2+ in one case, and negative in one case. HER2 gene amplification was positive in 3 cases, of which 2 cases showed a 3+ HER2 IHC score but one case was negative for HER2 IHC. Another 2 cases showed equivocal HER2 FISH results, and one remaining case was negative for HER2 FISH.Conclusion. Our observation that plasmacytoid urothelial carcinomas frequently demonstrated HER2 protein overexpression provides supporting evidence that HER2 may be a potential therapeutic target for plasmacytoid urothelial carcinoma.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiaoping Su ◽  
Xiaofan Lu ◽  
Sehrish Khan Bazai ◽  
Eva Compérat ◽  
Roger Mouawad ◽  
...  

Abstract Background Crosstalk between genetic, epigenetic, and immune alterations in upper tract urothelial carcinomas and their role in shaping muscle invasiveness and patient outcome are poorly understood. Results We perform an integrative genome- and methylome-wide profiling of diverse non-muscle-invasive and muscle-invasive upper tract urothelial carcinomas. In addition to mutations of FGFR3 and KDM6A, we identify ZFP36L1 as a novel, significantly mutated tumor suppressor gene. Overall, mutations of ZFP36 family genes (ZFP36, ZFP36L1, and ZFP36L2) are identified in 26.7% of cases, which display a high mutational load. Unsupervised DNA methylation subtype classification identifies two epi-clusters associated with distinct muscle-invasive status and patient outcome, namely, EpiC-low and EpiC-high. While the former is hypomethylated, immune-depleted, and enriched for FGFR3-mutated, the latter is hypermethylated, immune-infiltrated, and tightly associated with somatic mutations of SWI/SNF genes. Conclusions Our study delineates for the first time the key role for convergence between genetic and epigenetic alterations in shaping clinicopathological and immune upper tract urothelial carcinoma features.


2018 ◽  
Vol 60 (6) ◽  
pp. 496-503
Author(s):  
A.A. Painel Seguel ◽  
M.J. Martínez Pérez ◽  
T. Ripollés González ◽  
D.P. Gómez ◽  
J. Vizuete del Río ◽  
...  

2004 ◽  
Vol 84 (3) ◽  
pp. 215-223 ◽  
Author(s):  
Christian Rudlowski ◽  
Nicolaus Friedrichs ◽  
Andree Faridi ◽  
Lazlo Füzesi ◽  
Roland Moll ◽  
...  

2017 ◽  
Vol 11 (1) ◽  
pp. 51-57
Author(s):  
Abhishek Reekhaye ◽  
Seshadri Sriprasad ◽  
Sanjeev Madaan

Upper tract urothelial carcinoma (UTUC) is relatively rare and accounts for approximately 5% of all urothelial carcinomas. The estimated annual incidence of UTUC in Western countries is about two new cases per 100,000 inhabitants. The management of patients with upper tract urothelial carcinomas has changed significantly over the last decade with improved diagnostic techniques and treatment options. The gold-standard treatment used to be open radical nephroureterectomy with removal of the ipsilateral bladder cuff. The use of minimally invasive techniques for the diagnosis and management of upper urinary tract urothelial carcinoma is however expanding and has led to a paradigm shift in treatment strategies of upper tract urothelial carcinomas. In this article, we review the current diagnostic modalities and various endoscopic techniques being currently used in the management of this relatively rare tumour.


2019 ◽  
Vol 8 (6) ◽  
pp. 2971-2978 ◽  
Author(s):  
Wenbin Xue ◽  
Ping Tan ◽  
Hang Xu ◽  
Lu Yang ◽  
Qiang Wei

2018 ◽  
Vol 56 (2) ◽  
pp. 230-238 ◽  
Author(s):  
Luisa Vera Muscatello ◽  
Enrico Di Oto ◽  
Giuseppe Sarli ◽  
Valentina Monti ◽  
Maria Pia Foschini ◽  
...  

Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor overexpressed in a subset of breast cancer due to HER2 gene amplification. HER2 protein is expressed in feline mammary carcinomas, but little is known about its cytogenetic alterations. The aim of this study was to evaluate HER2 gene amplification status and its correlation with HER2 protein expression in feline mammary carcinomas. Feline mammary carcinomas were retrospectively selected and immunohistochemically (IHC) evaluated for HER2 protein expression. All the HER2 IHC-positive (3+) and equivocal (2+) cases and a subset of negative cases (0/1+) were selected for fluorescence in situ hybridization (FISH). Dual-core tissue microarrays were prepared for FISH. IHC and FISH were evaluated according to the 2013 American Society of Clinical Oncology/College of American Pathologists guidelines. The study included 107 feline mammary carcinomas from 88 queens. HER2 protein expression was positive (3+) in 7 cases (6.5%), equivocal (2+) in 48 cases (45%), and negative (0/1+) in 52 cases (48.5%). HER2 status was indeterminate in 8 feline mammary carcinomas (12%), amplified in 3 (4%), equivocal in 4 (6%), and nonamplified in 53 (78%). HER2 gene amplification and protein expression were significantly positively correlated ( R = 0.283; P < .0001). HER2 gene is amplified in a subset of feline mammary carcinomas despite the HER2 positive or equivocal protein expression, but it remains to be determined if the HER2 amplification is a gene alteration that drives mammary tumor carcinogenesis or only a bystander passenger mutation.


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