HER2 status in primary tumors and metastatic regional lymph nodes in patients with esophageal adenocarcinoma (EAC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4071-4071
Author(s):  
Harry H. Yoon ◽  
Qian Shi ◽  
William R. Sukov ◽  
Christopher A. Sattler ◽  
Rakhee Vaidya ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Lymph Nodes ◽  
Her2 Status ◽  
Her2 Amplification ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Regional Lymph Nodes ◽  
Primary Tumors ◽  
Routine Procedures

4071 Background: Selection of patients for HER2-targeted therapy is based on HER2 analysis in primary EACs. Since EACs metastasize via regional lymph nodes, concordance of HER2 gene amplification results between primary tumors and their metastatic lymph nodes (MLN) is a clinically important issue. Methods: Resected EACs (N = 103) having at least three distinct regional MLNs (total 508 MLNs; median 4 [range 3-11]) were sectioned using routine procedures and tested for HER2 amplification by fluorescence in situ hybridization (FISH). Primary tumors were also evaluated for HER2 protein expression by immunohistochemistry (IHC) and by FISH. Amplification was defined as HER2/CEP17 ≥ 2. IHC was scored as 0, 1+, 2+, or 3+. Primaries whose HER2 status was positive by both FISH and IHC (ie, amplified and IHC3+), or negative by both (ie, nonamplified and IHC0-1+), were selected. HER2 status was compared between primaries and their MLNs (kappa). Results: Concordant HER2 results between primaries and their MLNs were found in 92% (95/103) of EACs (Table; κ = .76 [95% CI .60 - .92]). However, among patients with HER2-positive primaries, 19% (4/21) had HER2-nonamplified MLNs; among these cases, either all MLNs were HER2-nonamplified (n = 2), or both HER2-nonamplified and –amplified MLNs were present (n = 2). Among HER2-negative primary EACs, 5% (4/82) of cases had MLNs that were all HER2-amplified (n = 3) or both HER2-nonamplified and -amplified (n = 1). Conclusions: A patient subset whose primary EACs were HER2-positive (by both FISH and IHC) were unexpectedly found to lack HER2 amplification in corresponding MLNs. Conversely, a subgroup with HER2-negative primaries had HER2-amplified MLNs, and would have been deemed ineligible for HER2-targeted therapy. These preliminary data suggest that evaluating MLNs in resected EACs has the potential to better identify patients who benefit from HER2-targeted therapy. [Table: see text]

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.

Mutations of HER2 gene in HER2-positive metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13118-13118 ◽  
Author(s):  
T. Prempree ◽  
C. Wongpaksa
Keyword(s):  
Breast Cancer ◽  
Gene Mutations ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Trastuzumab Resistance ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Primary Tumors ◽  
Trastuzumab Therapy ◽  
One Year

13118 Background: HER2 status of Breast Cancer has been assessed by IHC and FISH and used for therapeutic decision with a high degree of success. However, there were numbers of HER2-positive MBC who finally failed the Trastuzumab treatment after initial good response. Mechanisms of intrinsic and acquired Trastuzumab resistance are not yet known. Our Objective is to identify factor or factors responsible for Trastuzumab resistance. Methods: DNA extraction and Sequencing of HER2 gene were performed on primary tumors of HER2-positive 14 MBC patients undergoing Trastuzumab therapy. Re-biopsy were done on new metstatic sites of those cases discovered to have Trastuzumab resistance. Results: Of 14 MBC cases whose tumors showing positive IHC and FISH, there were no mutation found in their HER2 gene, exons 18,19, 20 and 21. However, 3 of 14 cases of MBC undergoing continuous Trastuzumab therapy with excellent response for more than one year, developed the resistance. All three cases had new metstatic sites biopsied, and showed D880N and E837Y mutations in the exon 21 of their HER2 genes. All three cases showed no response to trastuzumab therapy. Conclusions: 1) HER2-positive MBC tumors did not have any HER2 gene mutations in them. 2) Mutations arised in their HER2 gene, exon 21 may be responsible for the intrinsic and acquired Trastuzumab resistance. Additional work in this area is needed to further substantiate our findings. No significant financial relationships to disclose.

HER2 status testing by immunohistochemical and fFluorescence in situ hybridization in China

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22233-e22233
Author(s):  
W. Tao ◽  
J. Zefei ◽  
Z. Xuan ◽  
L. Xiaobing ◽  
Z. Shaohua ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Her2 Status ◽  
Central Laboratory ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Clinical Prognosis ◽  
Her2 Testing ◽  
Regional Laboratory

e22233 Background: HER2 gene overexpression is associated with aggressive breast cancer and poor clinical prognosis. Humanized anti-HER2 monoclonal antibody trastuzumab, which is targeted HER2 protein has showed to improve overall survival in patients with HER2-positive breast cancer in both the metastatic and adjuvant settings. There are some differences in HER2 positive rate among difference reports in China. This study tested HER2 status by immunohistochemistry(IHC) and fluorescence in situ hybridization (FISH) and compared HER2 testing at central and regional laboratories in China. Methods: Assessment of HER2 status was performed by FISH using the HercepTeast kit at central laboratory and by IHC using commercial available anti-HER2 probe in formalin-fixed and paraffin-embedded tissue section of 280 breast cancer samples. IHC HER2 testing was performed on 149 samples in the central laboratory. IHC HER2 testing was performed on 80 samples at both central laboratory and regional laboratory. Results: 280 samples were tested 373 times testing by IHC and FISH. The results were showed in table 1 . 80 samples was tested by IHC at central and regional laboratory and testing results of 36.4% samples were accordant (K=0.038). 94.1% IHC3+ at central laboratory were HER2 FISH positive and 83.3% IHC 3+ at regional laboratory were HER2 FISH positive. 86.7% IHC 2+ at central laboratory were HER2 FISH positive and 62.7% IHC 2+ at regional laboratory were HER2 FISH positive. 17 samples were observed HER2 FISH positive in the 27 IHC 0/1+ tested at regional laboratoty. So good correlation was obsearved between FISH HER2 status and IHC results from central laboratory but not from regional laboratory. Conclusions: This study emphasized the important of accurate HER2 testing. HER2 FISH test should be performed for the IHC 2+ samples. Even HER2 FISH test maybe performed for IHC 0/1 sample according to clinical characteristics in China in order to make the patients have targeted therapy chance. [Table: see text] No significant financial relationships to disclose.

Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4010-4010 ◽  
Author(s):  
Michael Alexander Gordon ◽  
Holly Gundacker ◽  
Jacqueline Benedetti ◽  
John S. Macdonald ◽  
Joaquina Celebre Baranda ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Radiation Therapy ◽  
In Situ Hybridization ◽  
Gene Amplification ◽  
Phase Iii ◽  
Her2 Status ◽  
Her2 Amplification ◽  
Her2 Gene ◽  
Her2 Gene Amplification

4010 Background: Trastuzumab has been approved for treatment of patients with HER2-positive metastatic gastric carcinoma; however, relatively little is known about the role of HER2 in the natural history of this disease. Methods: Patients enrolled in the INT-0116/SWOG9008 phase III gastric cancer clinical trial (n=559) were retrospectively evaluated for HER2 gene amplification by fluorescence in situ hybridization (FISH)(n=258), overexpression by immunohistochemistry (IHC)(n=148) and HER2 amplification by silver-enhanced in situ hybridization (n=77) based on availability of tissue specimens. The purpose of the original clinical trial was to evaluate the benefit of post-operative 5-fluorouracil/leucovorin plus radiation therapy compared to surgery alone. Results: HER2 gene amplification rate by FISH was 10.9% in tumor tissue from 258 patients evaluated. HER2 status determined by FISH was 92% concordant with SISH. HER2 overexpression rate by IHC was 12.2% among 148 patients evaluated, with 90% agreement between FISH and IHC. There was a significant interaction between HER2 status by FISH and treatment with respect to both OS (p=0.034) and DFS (p=0.020). Among patients with HER2 non-amplified cancers, treated patients had a median OS of 44 months compared to 24 months for patients in the surgery only arm (34 and 17 months respectively for DFS, p=0.003). Among 28 patients with HER2 amplified cancers, the medians for OS were 16 months in the treated arm, and 22 months in the surgery arm (p=0.55) (13 and 11 months respectively for DFS, p=0.87). We were unable to detect a statistically significant treatment benefit in this small subset of patients with HER2 amplification. HER2 amplification status was not an independent prognostic marker of OS among patients who received no postoperative chemotherapy or radiation therapy (p=0.76). Conclusions: Patients lacking HER2 amplification responded significantly to treatment as indicated by both OS and DFS.

scholarly journals HER2-Positive Neuroendocrine Breast Cancer: Case Report and Review of Literature

Breast Care ◽  
2016 ◽  
Vol 11 (6) ◽  
pp. 424-426 ◽  
Author(s):  
Arpine Gevorgyan ◽  
Giacomo Bregni ◽  
Giulia Galli ◽  
Elisa Zanardi ◽  
Filippo de Braud ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Case Report ◽  
Targeted Therapy ◽  
Neuroendocrine Carcinoma ◽  
Immunohistochemical Analysis ◽  
Breast Cancer Case ◽  
Cancer Case ◽  
Review Of Literature ◽  
Her2 Amplification ◽  
Her2 Positive

Background: Neuroendocrine carcinoma is an uncommon histology for breast cancer. Case Report: Our patient underwent right quadrantectomy for a neuroendocrine carcinoma in 1984 and had a bone relapse 30 years later. After thorough pathological and immunohistochemical analysis the diagnosis was confirmed and HER2 amplification was observed. Here we discuss the management, rationale and results of HER2-targeted therapy in advanced neuroendocrine breast carcinoma.

scholarly journals Her2-Targeted Therapy Induces Autophagy in Esophageal Adenocarcinoma Cells

2018 ◽  
Vol 19 (10) ◽  
pp. 3069 ◽  
Author(s):  
Félice Janser ◽  
Olivia Adams ◽  
Vanessa Bütler ◽  
Anna Schläfli ◽  
Bastian Dislich ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Esophageal Adenocarcinoma ◽  
Acquired Resistance ◽  
Therapy Resistance ◽  
Her2 Status ◽  
Autophagic Flux ◽  
Cancer Type ◽  
Cancer Resistance ◽  
Her2 Positive ◽  
Autophagy Inhibition

Esophageal adenocarcinoma (EAC) is a highly lethal cancer type with an overall poor survival rate. Twenty to thirty percent of EAC overexpress the human epidermal growth factor receptor 2 (Her2), a transmembrane receptor tyrosine kinase promoting cell growth and proliferation. Patients with Her2 overexpressing breast and gastroesophageal cancer may benefit from Her2 inhibitors. Therapy resistance, however, is well documented. Since autophagy, a lysosome-dependent catabolic process, is implicated in cancer resistance mechanisms, we tested whether autophagy modulation influences Her2 inhibitor sensitivity in EAC. Her2-positive OE19 EAC cells showed an induction in autophagic flux upon treatment with the small molecule Her2 inhibitor Lapatinib. Newly generated Lapatinib-resistant OE19 (OE19 LR) cells showed increased basal autophagic flux compared to parental OE19 (OE19 P) cells. Based on these results, we tested if combining Lapatinib with autophagy inhibitors might be beneficial. OE19 P showed significantly reduced cell viability upon double treatment, while OE19 LR were already sensitive to autophagy inhibition alone. Additionally, Her2 status and autophagy marker expression (LC3B and p62) were investigated in a treatment-naïve EAC patient cohort (n = 112) using immunohistochemistry. Here, no significant correlation between Her2 status and expression of LC3B and p62 was found. Our data show that resistance to Her2-directed therapy is associated with a higher basal autophagy level, which is not per se associated with Her2 status. Therefore, we propose that autophagy may contribute to acquired resistance to Her2-targeted therapy in EAC, and that combining Her2 and autophagy inhibition might be beneficial for EAC patients.

scholarly journals Different pathologic responses to neoadjuvant anti-PD-1 in primary squamous lung cancer and regional lymph nodes

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Yun Ling ◽  
Ning Li ◽  
Lin Li ◽  
Changyuan Guo ◽  
Jiacong Wei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lymph Nodes ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Regional Lymph Nodes ◽  
Primary Tumors ◽  
Neoadjuvant Immunotherapy ◽  
Squamous Lung Cancer ◽  
Nsclc Patients ◽  
Residual Viable Tumor

AbstractNeoadjuvant immunotherapy provides a unique opportunity for understanding therapeutic responses. We analyzed pathologic responses in surgical specimens obtained from 31 squamous non-small cell lung cancer (NSCLC) patients receiving neoadjuvant anti-PD-1 treatment. Fifteen (48.4%) patients achieved pathologic complete response (pCR) or major pathologic response (MPR). Among them, seven (46.7%) were assessed as radiological partial response and eight (53.3%) as stable disease. Among 20 patients with pathologically identified tumor beds in lymph nodes (LNs), 10 and six patients achieved pCR/MPR in primary tumors and paired LNs, respectively. pCR was achieved in 6/19 N1 nodes and 1/7 N2 nodes. Residual viable tumor (RVT) cells in 8/9 MPR specimens had 100% immune-activated phenotype, while a median of 80% of RVT cells in pathologic nonresponse specimens presented immune-excluded/desert phenotype. These findings demonstrated that assessment of pathologic responses in both primary tumor and LNs may be important as a surrogate for assessing neoadjuvant immunotherapeutic efficacy.

Comparison of HER2 Status by Fluorescence in Situ Hybridization and Immunohistochemistry to Predict Benefit From Dose Escalation of Adjuvant Doxorubicin-Based Therapy in Node-Positive Breast Cancer Patients

2005 ◽  
Vol 23 (19) ◽  
pp. 4287-4297 ◽  
Author(s):  
Lynn G. Dressler ◽  
Donald A. Berry ◽  
Gloria Broadwater ◽  
David Cowan ◽  
Kelly Cox ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Cancer Patients ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Node Positive ◽  
Positive Breast Cancer

Purpose HER2 is a clinically important tumor marker in breast cancer; however, there is controversy regarding which method reliably measures HER2 status. We compared three HER2 laboratory methods: immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR), to predict disease-free survival (DFS) and overall survival (OS) after adjuvant doxorubicin-based therapy in node-positive breast cancer patients. Methods This is a Cancer and Leukemia Group B (CALGB) study, using 524 tumor blocks collected from breast cancer patients registered to clinical trial CALGB 8541. IHC employed CB11 and AO-11-854 monoclonal antibodies; FISH used PathVysion HER2 DNA Probe kit; PCR utilized differential PCR (D-PCR) methodology. Results Cases HER2 positive by IHC, FISH and D-PCR were 24%, 17%, and 18%, respectively. FISH and IHC were clearly related (κ = 64.8%). All three methods demonstrated a similar relationship for DFS and OS. By any method, for patients with HER2-negative tumors, there was little or no effect of dose of adjuvant doxorubicin-based therapy. For patients with HER2-positive tumors, all three methods predicted a benefit from dose-intense (high-dose) compared with low- or moderate-dose adjuvant doxorubicin-based therapy. Conclusion FISH is a reliable method to predict clinical outcome following adjuvant doxorubicin-based therapy for stage II breast cancer patients. There is a moderate level of concordance among the three methods (IHC, FISH, PCR). None of the methods is clearly superior. Although IHC-positive/FISH-positive tumors yielded the greatest interaction with dose of therapy in predicting outcome, no combination of assays tested was statistically superior.

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