Her2 amplification distinguishes a subset of non-muscle-invasive bladder cancers with a high risk of progression

2012 ◽  
Vol 66 (2) ◽  
pp. 113-119 ◽  
Author(s):  
Paul Chih-Hsueh Chen ◽  
Hui-Jung Yu ◽  
Yen-Hwa Chang ◽  
Chin-Chen Pan
Keyword(s):  
In Situ Hybridisation ◽  
Her2 Status ◽  
Low Grade ◽  
Fluorescence In Situ Hybridisation ◽  
High Grade ◽  
Her2 Amplification ◽  
Her2 Gene ◽  
Tissue Arrays ◽  
Urothelial Carcinomas ◽  
Muscle Invasive

BackgroundSeveral studies have employed immunohistochemistry to detect Her2/neu overexpression in urothelial carcinomas, yielding a tremendous range of positive expression rates. Few studies have examined Her2 status in non-muscle invasive bladder cancer (NMIBC) using fluorescence in situ hybridisation (FISH).AimTo evaluate Her2 amplification in NMIBC (Ta/T1), to correlate the findings with recurrence and progression, and compare the Her2 status between primary and progressive tumours.MethodsFISH and immunohistochemistry for Her2/neu were performed on tissue arrays consisting of 36 papillary urothelial neoplasms of low malignant potential (PUNLMPs), 190 low grade urothelial carcinomas (LG-UCs) and 178 high grade urothelial carcinomas (HG-UCs). 32 cases with specimens of both primary and progressive tumours (from Ta/T1 to T2–4) were included for comparative analyses.Results16 HG-UCs (9.0%) showed Her2 gene amplification while none of the PUNLMPs and LG-UCs showed this aberration. There was 100% concordance in the status of Her2 amplification between primary and progressive lesions. Immunohistochemistry and FISH results were in closest agreement when overexpression was defined as 50% of tumour cells showing immunoreactivity. The cumulative incidences of recurrence and progression in Her2-amplified HG-UC were significantly higher than in those without amplification.ConclusionsA subset of high-grade NMIBCs contain Her2 amplification and are associated with markedly aggressive behaviour. Her2 diagnostics are valuable for distinguishing patients who require diligent surveillance and would potentially benefit from anti-Her2 therapies.

scholarly journals ESR1 Amplification is Rare in Breast Cancer and is Associated with High Grade and High Proliferation: A Multiplex Ligation-Dependent Probe Amplification Study

2010 ◽  
Vol 33 (1) ◽  
pp. 13-18 ◽  
Author(s):  
Cathy B. Moelans ◽  
Hanneke N. Monsuur ◽  
Johannes H. de Pinth ◽  
Remco D. Radersma ◽  
Roel A. de Weger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
In Situ Hybridisation ◽  
Therapy Response ◽  
Low Grade ◽  
Fluorescence In Situ Hybridisation ◽  
High Grade ◽  
Breast Cancer Patients ◽  
Frequent Event ◽  
Dependent Probe

Background: Expression of estrogen receptor alpha (ERα) is predictive for endocrine therapy response and an important prognostic factor in breast cancer. Overexpression of ERα can be caused by estrogen receptor 1 (ESR1) gene amplification and was originally reported to be a frequent event associated with a significantly longer survival for ER-positive women treated with adjuvant tamoxifen monotherapy, which was however questioned by subsequent studies.Methods: This study aimed to reanalyze the frequency of ESR1 amplification by multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridisation (FISH), and to assess clinicopathologic correlations. MLPA was performed in a group of 135 breast cancer patients, and gains/amplifications were subjected to FISH.Results: True ESR1 amplification by MLPA was rare (2%) and only 6% more patients showed a modest gain of ESR1. All MLPA-detected ESR1 amplifications and nearly all ESR1 gains were also FISH amplified and gained, but not all FISH amplifications/gains were MLPA amplified/gained, leading to an overall concordance of only 60% between both techniques. All 3 MLPA and FISH ESR1 amplified cases had high ERα expression, but there was no obvious correlation between ESR1 gain and ER status by IHC. ESR1 gains/amplifications were not associated with HER2 gain/amplification, but seemed to be associated with older age. Surprisingly, ESR1 gain/amplification was not associated with low grade as reported previously, but correlated with high grade and high proliferation. Furthermore, ESR1 gain/amplification by MLPA was not associated with nodal status or tumor size (pT status).Conclusion: ESR1 amplification as detected by MLPA is rare in breast cancer, and seems to be associated with high ERα expression, high age, high grade and high proliferation. This study confirms previous studies that showed differences in the ESR1 amplification frequencies detected by different techniques.

scholarly journals Detection of HER2 Amplification in Breast Carcinomas: Comparison of Multiplex Ligation-Dependent Probe Amplification (MLPA) and Fluorescence In Situ Hybridization (FISH) combined with Automated Spot Counting

2006 ◽  
Vol 28 (4) ◽  
pp. 151-159
Author(s):  
Elna Moerland ◽  
Rens L. H. P. M. van Hezik ◽  
Toine C. J. M. van der Aa ◽  
Mike W. P. M. van Beek ◽  
Adriaan J. C. van den Brule
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Gene Amplification ◽  
Her2 Status ◽  
Her2 Amplification ◽  
Breast Carcinomas ◽  
Her2 Gene ◽  
Her2 Gene Amplification ◽  
Dependent Probe

In this study the detection of HER2 gene amplification was evaluated using Fluorescence In Situ Hybridization (FISH; PathVysion) in comparison with Multiplex Ligation-dependent Probe Amplification (MLPA), a PCR based technique. These two methods were evaluated on a series of 46 formalin fixed paraffin embedded breast carcinomas, previously tested for protein overexpression by HercepTest (grouped into Hercep 1+, 2+ and 3+). HER2 gene amplification (ratio ≥ 2.0) by FISH was found in 9/10, 10/30 and 0/6 in IHC 3+, 2+ and 1+/0 cases, respectively. Digitalized automated spot counting performed with recently developed CW4000 CytoFISH software was 100% concordant with manual FISH scoring. Using MLPA 18/46 samples showed a clear HER2 amplification. Comparing MLPA and IHC showed the same results as for FISH and IHC. All but one FISH positive cases (18/19) were confirmed by MLPA for the presence of the gene amplification. The overall concordance of detection of Her2 gene amplification by FISH and MLPA was 98% (45/46). Furthermore, both the level of amplification and equivocal results correlated well between both methods. In conclusion, MLPA is a reliable and reproducible technique and can be used as an either alternative or additional test to determine HER2 status in breast carcinomas.

scholarly journals HER2 Amplification Status in Feline Mammary Carcinoma: A Tissue Microarray–Fluorescence In Situ Hydridization–Based Study

2018 ◽  
Vol 56 (2) ◽  
pp. 230-238 ◽  
Author(s):  
Luisa Vera Muscatello ◽  
Enrico Di Oto ◽  
Giuseppe Sarli ◽  
Valentina Monti ◽  
Maria Pia Foschini ◽  
...  
Keyword(s):  
Protein Expression ◽  
Gene Amplification ◽  
Her2 Status ◽  
Tyrosine Kinase Receptor ◽  
Her2 Amplification ◽  
Her2 Gene ◽  
Her2 Protein ◽  
Mammary Carcinomas ◽  
Her2 Gene Amplification

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.

scholarly journals Interobserver reproducibility of The Paris System for Reporting Urinary Cytology

CytoJournal ◽  
2017 ◽  
Vol 14 ◽  
pp. 17 ◽  
Author(s):  
Theresa Long ◽  
Lester J. Layfield ◽  
Magda Esebua ◽  
Shellaine R. Frazier ◽  
D. Tamar Giorgadze ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Urinary Cytology ◽  
Low Grade ◽  
High Grade ◽  
Urothelial Cells ◽  
Urothelial Carcinomas ◽  
Absolute Agreement ◽  
Potential Impact ◽  
Urine Specimens

Background: The Paris System for Reporting Urinary Cytology represents a significant improvement in classification of urinary specimens. The system acknowledges the difficulty in cytologically diagnosing low-grade urothelial carcinomas and has developed categories to deal with this issue. The system uses six categories: unsatisfactory, negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells, suspicious for high-grade urothelial carcinoma, high-grade urothelial carcinoma, other malignancies and a seventh subcategory (low-grade urothelial neoplasm). Methods: Three hundred and fifty-seven urine specimens were independently reviewed by four cytopathologists unaware of the previous diagnoses. Each cytopathologist rendered a diagnosis according to the Paris System categories. Agreement was assessed using absolute agreement and weighted chance-corrected agreement (kappa). Disagreements were classified as low impact and high impact based on the potential impact of a misclassification on clinical management. Results: The average absolute agreement was 65% with an average expected agreement of 44%. The average chance-corrected agreement (kappa) was 0.32. Nine hundred and ninety-nine of 1902 comparisons between rater pairs were in agreement, but 12% of comparisons differed by two or more categories for the category NHGUC. Approximately 15% of the disagreements were classified as high clinical impact. Conclusions: Our findings indicated that the scheme recommended by the Paris System shows adequate precision for the category NHGUC, but the other categories demonstrated unacceptable interobserver variability. This low level of diagnostic precision may negatively impact the applicability of the Paris System for widespread clinical application.

scholarly journals Urothelial Tumors of the Urinary Bladder in Young Patients: A Clinicopathologic Study of 59 Cases

2013 ◽  
Vol 137 (10) ◽  
pp. 1337-1341 ◽  
Author(s):  
Melissa L. Stanton ◽  
Li Xiao ◽  
Bogdan A. Czerniak ◽  
Charles C. Guo
Keyword(s):  
Urinary Bladder ◽  
Clinical Outcomes ◽  
Young Patients ◽  
Muscularis Propria ◽  
Low Grade ◽  
High Grade ◽  
Urothelial Carcinomas ◽  
Pathologic Features ◽  
Urothelial Tumors

Context.—Urothelial tumors are rare in young patients. Because of their rarity, the natural history of the disease in young patients remains poorly understood. Objective.—To understand the pathologic and clinical features of urothelial tumors of the urinary bladder in young patients. Design.—We identified 59 young patients with urothelial tumors of the urinary bladder treated at our institution and analyzed the tumors' pathologic features and the patients' clinical outcomes. Results.—All patients were 30 years or younger, with a mean age of 23.5 years (range, 4–30). Thirty-eight patients (64%) were male, and 21 (36%) were female. Most tumors were noninvasive, papillary urothelial tumors (49 of 59; 83%), including papillary urothelial neoplasms of low malignant potential (7 of 49; 14%), low-grade papillary urothelial carcinomas (38 of 49; 78%), and high-grade papillary urothelial carcinomas (4 of 49; 8%). Only a few (n = 10) of the urothelial tumors were invasive, invading the lamina propria (n = 5; 50%), muscularis propria (n = 4; 40%), or perivesical soft tissue (n = 1; 10%). Clinical follow-up information was available for 41 patients (69%), with a mean follow-up time of 77 months. Of 31 patients with noninvasive papillary urothelial tumors, only 1 patient (3%) later developed an invasive urothelial carcinoma and died of the disease, and 30 of these patients (97%) were alive at the end of follow-up, although 10 (32%) had local tumor recurrences. In the 10 patients with invasive urothelial carcinomas, 3 patients (30%) died of the disease and 5 others (50%) were alive with metastases (the other 2 [20%] were alive with no recurrence). Conclusion.—Urothelial tumors in young patients are mostly noninvasive, papillary carcinomas and have an excellent prognosis; however, a small subset of patients may present with high-grade invasive urothelial carcinomas that result in poor clinical outcomes.

HER2 status in 146 gastroesophageal carcinomas assessed by two rabbit monoclonal antibodies (SP3 and 4B5) and two in situ hybridisation methods (FISH and SISH)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15555-e15555
Author(s):  
J. E. Boers ◽  
H. Meeuwissen ◽  
N. Methorst
Keyword(s):  
Negative Predictive Value ◽  
Predictive Value ◽  
In Situ Hybridisation ◽  
Gastric Cardia ◽  
Phase Iii ◽  
Gastric Body ◽  
Her2 Status ◽  
Her2 Amplification ◽  
Distal Stomach ◽  
Her2 Positivity

e15555 Background: In the industrialized world, the incidence of adenocarcinomas of the distal esophagus/gastric cardia is increasing rapidly and though the incidence of carcinomas of the gastric body / antrum are decreasing they still represent a significant health problem. Several reports claim a significant HER2-positivity in gastro-esophageal adenocarcinomas. A large phase III trial in which HER2-positive gastric cancer patients are treated with trastuzumab is ongoing. New HER2 assessment methods are gaining popularity in breast cancer. Methods: HER2 status was examined in gastro-esophageal carcinomas, comparing SP3 (Labvision) and 4B5 (Ventana) immunohistochemistry (IHC), conventional dual probe HER2 FISH (DAKO), and SISH (Ventana) in a single Dutch institution. Results: IHC was carried out on biopsies of 146 patients with adenocarcinomas of the esophagus (n=44), gastric cardia (n=28), body (n=24) and antrum (n=50). IHC positivity, as defined by an immunoscore 2+ or 3+ using a modified scoring system, was present in 17 cases with the SP3 antibody, and in 24 cases with 4B5. FISH/SISH showed identical results in 40 cases carried out when any immunoreactivity in either antibody was detected. 100% of SP3-IHC-positive cases, and 92% of 4B5-IHC-positive were amplified. The negative predictive value of SP3 and 4B5 (immunoscores 0/1+) was 77% and 95%, respectively. Heterogenous HER2- positivity with partial staining/amplification was present in 73% of the adenocarcinomas, occasionally with only a tumor area of 10–20% showing positivity. HER2-amplification was present in 27% of esophageal and 18% in gastric cardia carcinomas (resulting in 24% amplification of tumors of the esophago-gastric region). In the distal stomach, 7% HER2-amplification was seen. Conclusions: HER2 amplification is present in a significant proportion of esophago-gastric region adenocarcinomas (24%) but at a much lower rate in the distal stomach (7%). Both antibodies can be used for initial screening for possible amplification though the 4B5 antibody has the highest negative predictive value. FISH and SISH yield identical results but the SISH assay offers rapid assessment. [Table: see text]

scholarly journals HER2 Protein Overexpression and Gene Amplification in Plasmacytoid Urothelial Carcinoma of the Urinary Bladder

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Bohyun Kim ◽  
Gilhyang Kim ◽  
Boram Song ◽  
Cheol Lee ◽  
Jeong Hwan Park ◽  
...  
Keyword(s):  
Protein Expression ◽  
Urothelial Carcinoma ◽  
Gene Amplification ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Supporting Evidence ◽  
Protein Overexpression ◽  
Her2 Gene ◽  
Her2 Protein ◽  
Urothelial Carcinomas

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.

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