Gene amplification and protein expression of EGFR and HER2 by chromogenic in situ hybridisation and immunohistochemistry in atypical adenomatous hyperplasia and adenocarcinoma of the lung

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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Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer

Oncology Reports ◽

10.3892/or.15.1.65 ◽

2006 ◽

Cited By ~ 19

Author(s):

Tomonori Yano ◽

Toshihiko Doi ◽

Atsushi Ohtsu ◽

Narikazu Boku ◽

Kaoru Hashizume ◽

...

Keyword(s):

Gastric Cancer ◽

In Situ Hybridization ◽

Protein Expression ◽

Fluorescence In Situ Hybridization ◽

Gene Amplification ◽

Her2 Gene ◽

Her2 Protein ◽

Her2 Gene Amplification

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Identification of MET genomic amplification, protein expression and alternative splice isoforms in neuroblastomas

Journal of Clinical Pathology ◽

10.1136/jclinpath-2012-201375 ◽

2013 ◽

Vol 66 (11) ◽

pp. 985-991 ◽

Cited By ~ 10

Author(s):

Benedict Yan ◽

Malcolm Lim ◽

Lihan Zhou ◽

Chik Hong Kuick ◽

May Ying Leong ◽

...

Keyword(s):

Protein Expression ◽

Kinase Inhibitor ◽

In Situ Hybridisation ◽

Genomic Amplification ◽

Splice Isoforms ◽

Anaplastic Lymphoma ◽

Met Amplification ◽

Alternatively Spliced ◽

Expression Status

BackgroundCrizotinib, a dual anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition (MET) tyrosine kinase inhibitor, is currently being evaluated for the treatment of neuroblastoma. Its effects are thought to be mediated mainly via its activity against ALK. Although MET genomic/protein expression status might conceivably affect crizotinib efficacy, this issue has hitherto not received attention in neuroblastomas.Aims/MethodsMET genomic and protein expression status was characterised by silver in situ hybridisation and immunohistochemistry (IHC) respectively, in a cohort of 54 neuroblastoma samples. MET splice isoforms were characterised in 15 of these samples by quantitative PCR.ResultsOne case (1/54; prevalence 1.85%) displayed MET genomic amplification, while another case (1/54; prevalence 1.85%) displayed strong membranous MET protein expression (IHC score 3+). Alternative exon 10-deleted and exon 14-deleted MET splice isoforms were identified.ConclusionsMET amplification and protein expression, although low in prevalence, are present in neuroblastomas. This has implications when crizotinib is employed as a therapeutic agent in neuroblastomas. Additionally, the existence of alternatively spliced MET isoforms may have clinical and biological implications in neuroblastomas.

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Solitary pulmonary capillary hemangioma presents as ground glass opacity on computed tomography indicating adenocarcinoma in situ/atypical adenomatous hyperplasia: A case report

Biomedical Reports ◽

10.3892/br.2017.997 ◽

2017 ◽

Author(s):

Yanmei Zhu ◽

Ning Qu ◽

Lili Sun ◽

Xiao Meng ◽

Xiaoyan Li ◽

...

Keyword(s):

Computed Tomography ◽

Case Report ◽

Ground Glass Opacity ◽

Capillary Hemangioma ◽

Ground Glass ◽

Adenocarcinoma In Situ ◽

Atypical Adenomatous Hyperplasia ◽

Adenomatous Hyperplasia ◽

Pulmonary Capillary

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DNA Methylation Changes in Atypical Adenomatous Hyperplasia, Adenocarcinoma In Situ, and Lung Adenocarcinoma

PLoS ONE ◽

10.1371/journal.pone.0021443 ◽

2011 ◽

Vol 6 (6) ◽

pp. e21443 ◽

Cited By ~ 70

Author(s):

Suhaida A. Selamat ◽

Janice S. Galler ◽

Amit D. Joshi ◽

M. Nicky Fyfe ◽

Mihaela Campan ◽

...

Keyword(s):

Dna Methylation ◽

Lung Adenocarcinoma ◽

Adenocarcinoma In Situ ◽

Atypical Adenomatous Hyperplasia ◽

Adenomatous Hyperplasia

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Gene copy number of epidermal growth factor receptor (EGFR) by fluorescent in situ hybridization (FISH) in head and neck squamous cell carcinomas (HNSCC) is closely correlated with EGFR protein levels assessed by automated quantitative protein analysis (AQUA)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.6023 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 6023-6023

Author(s):

P. Weinberger ◽

A. Psyrri ◽

P. Kountourakis ◽

T. Rampias ◽

C. Sasaki ◽

...

Keyword(s):

In Situ Hybridization ◽

Protein Expression ◽

Protein Content ◽

Gene Amplification ◽

Copy Number ◽

Gene Copy Number ◽

Gene Copy ◽

Egfr Gene ◽

Protein Levels

6023 Background: EGFR overexpression correlates with recurrence and with treatment resistance in HNSCC. The mechanisms of EGFR protein overexpression are poorly understood. Nonetheless, previous investigators have not demonstrated a correlation between EGFR gene copy number and protein content, using conventional immunohistochemistry (IHC). The aim of this study was to evaluate the relationship of EGFR gene copy number and protein expression utilizing fluorescence in situ hybridization (FISH) and AQUA, a novel, immunohistochemical method of automated quantitative in situ proteomic analysis which permits subcellular localization. Methods: A tissue microarray composed of 137 HNSCC treated with (chemo)radiation was constructed and analyzed for EGFR copy number by FISH (Vysis/Abbot) and EGFR protein expression (DAKO antibody) using AQUA analysis of EGFR staining scored on a scale of 0–255 and by conventional IHC. Agreement was assessed using kappa. Results: Sixteen (15%) of one-hundred six tumors with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH+). AQUA demonstrated a range of 3.6–102.2; protein levels assessed by AQUA in the FISH amplified cases were significantly higher (p =0.008) than in the FISH non- amplified ones. Using the EGFR 75th percentile as a cut-off, AQUA and FISH showed significant agreement (percentage of overall agreement 82%, kappa=0.458, p=0.003). To the contrary there was no concordance between FISH and conventional IHC results in this series. Conclusions: The discrepancy between EGFR gene amplification rate and protein expression by IHC reported previously may be due to the limitations and nonquantitative nature of conventional IHC. EGFR protein content correlates with gene copy number if protein content is quantitated and automatically analyzed, as with AQUA. No significant financial relationships to disclose.

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