Change in Pattern of HER2 Fluorescent in Situ Hybridization (FISH) Results in Breast Cancers Submitted for FISH Testing: Experience of a Reference Laboratory Using US Food and Drug Administration Criteria and American Society of Clinical Oncology and College of American Pathologists Guidelines

2016 ◽  
Vol 34 (29) ◽  
pp. 3502-3510 ◽  
Author(s):  
Mithun Vinod Shah ◽  
Anne E. Wiktor ◽  
Reid G. Meyer ◽  
Kathleen S. Tenner ◽  
Karla V. Ballman ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Drug Administration ◽  
Mayo Clinic ◽  
Fluorescent In Situ Hybridization ◽  
Food And Drug Administration ◽  
Chromosome 17 ◽  
Reference Laboratory ◽  
Her2 Positive ◽  
Her2 Testing

Purpose In 1998, the US Food and Drug Administration (FDA) approved human epidermal growth factor receptor 2 (HER2) testing guidelines to determine eligibility for HER2-directed therapy (HDT) in breast cancer. ASCO and the College of American Pathologists published immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) HER2 testing guidelines in 2007 (AC2007) and updated these guidelines in 2013 (AC2013). We compared the HER2 FISH amplification frequency using these three guidelines. Methods Patient samples that were sent to the Mayo Clinic cytogenetics laboratory for FISH testing (n = 2,851; from November 2013 to October 2014) were analyzed. Frequency of HER2 FISH amplification was examined and impact of AC2013 assessed. Results IHC results were available for 1,922 patient samples (67.4%), 137 of which were from Mayo Clinic. Distribution was 2.4% IHC 0, 7.9% IHC 1+, 84.8% IHC 2+, and 2.5% IHC 3+. Among IHC 2+ patients, HER2 FISH positivity was 11.8% (FDA), 9.4% (AC2007), and 24.1% (AC2013). Overall, 11.8% (n = 339) were positive with a FISH ratio ≥ 2.0, 1.3% (n = 35) with a FISH ratio ≥ 2.0 despite a HER2 signal < 4.0, and 3.0% (n = 86) with HER2 signal ≥ 6.0 despite FISH ratio < 2.0. Among 405 patients (14.2%) who were initially considered FISH-equivocal (ratio < 2.0 with HER2 signal ≥ 4.0, but < 6.0; AC2013), use of an alternative chromosome 17 probe reassigned 212 (7.4% overall) patients to FISH-positive and 36 (1.3% overall) patients to FISH-negative, whereas 157 (5.5% overall) patients remained equivocal. Final HER2 positivity with AC2013 (23.6%) was increased (P < .001) compared with FDA (13.1%) and AC2007 (11%) guidelines. Conclusion In a reference laboratory cohort that was highly enriched for IHC 2+ patient samples, AC2013 guidelines led to a larger number of FISH-equivocal patients. Approximately one half of these FISH-equivocal patients (7.4% overall) became HER2-positive upon alternative FISH probe testing. However, these patients would not have participated in the pivotal HDT trials. Clinical utility data on HDT benefit in these patients and other special subsets are needed.

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.

Detection of an i(17q) chromosome by fluorescent in situ hybridization with a chromosome 17 alpha satellite DNA probe

1992 ◽  
Vol 62 (2) ◽  
pp. 140-143 ◽  
Author(s):  
Hitoshi Nakagawa ◽  
Johji Inazawa ◽  
Shinichi Misawa ◽  
Shinji Tanaka ◽  
Teruyuki Takashima ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Satellite Dna ◽  
Fluorescent In Situ Hybridization ◽  
Dna Probe ◽  
Chromosome 17 ◽  
Alpha Satellite ◽  
Alpha Satellite Dna

Predicting Anthracycline Benefit: TOP2A and CEP17—Not Only but Also

2015 ◽  
Vol 33 (15) ◽  
pp. 1680-1687 ◽  
Author(s):  
John M.S. Bartlett ◽  
Christopher C. McConkey ◽  
Alison F. Munro ◽  
Christine Desmedt ◽  
Janet A. Dunn ◽  
...  
Keyword(s):  
Overall Survival ◽  
In Situ Hybridization ◽  
Fluorescent In Situ Hybridization ◽  
Meta Analysis ◽  
Predictive Biomarkers ◽  
Pooled Analysis ◽  
Hazard Ratio ◽  
Chromosome 17 ◽  
Individual Patient Level

Purpose Evidence supporting the clinical utility of predictive biomarkers of anthracycline activity is weak, with a recent meta-analysis failing to provide strong evidence for either HER2 or TOP2A. Having previously shown that duplication of chromosome 17 pericentromeric alpha satellite as measured with a centromere enumeration probe (CEP17) predicted sensitivity to anthracyclines, we report here an individual patient–level pooled analysis of data from five trials comparing anthracycline-based chemotherapy with CMF (cyclophosphamide, methotrexate, and fluorouracil) as adjuvant chemotherapy for early breast cancer. Patients and Methods Fluorescent in situ hybridization for CEP17, HER2, and TOP2A was performed in three laboratories on samples from 3,846 of 4,864 eligible patients from five trials evaluating anthracycline-containing chemotherapy versus CMF. Methodologic differences did not affect HER2-to-CEP17 ratios but necessitated different definitions for CEP17 duplication: > 1.86 observed copies per cell for BR9601, NEAT, Belgian, and DBCG89D trials and > 2.25 for the MA.5 trial. Results Fluorescent in situ hybridization data were available in 89.3% (HER2), 83.9% (CEP17), and 80.6% (TOP2A) of 3,846 patient cases with available tissue. Both CEP17and TOP2A treatment-by-marker interactions remained significant in adjusted analyses for recurrence-free and overall survival, whereas HER2 did not. A combined CEP17 and TOP2A–adjusted model predicted anthracycline benefit across all five trials for both recurrence-free (hazard ratio, 0.64; 95% CI, 0.51 to 0.82; P = .001) and overall survival (hazard ratio, 0.66; 95% CI, 0.51 to 0.85; P = .005). Conclusion This prospectively planned individual-patient pooled analysis of patient cases from five adjuvant trials confirms that patients whose tumors harbor either CEP17 duplication or TOP2A aberrations, but not HER2 amplification, benefit from adjuvant anthracycline chemotherapy.

scholarly journals Low Level ofHer-2Locus Amplification by Fluorescent In Situ Hybridization Does Not Correlate with Her-2 Protein Overexpression by Immunohistochemistry in Barrett's Esophagus

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Agnieszka M. Rygiel ◽  
Francesca Milano ◽  
Fiebo J. ten Kate ◽  
Jacques J. G. H. M. Bergman ◽  
Kausillia K. Krishnadath
Keyword(s):  
In Situ Hybridization ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Fluorescent In Situ Hybridization ◽  
Chromosome 17 ◽  
Protein Overexpression ◽  
Therapeutic Implications ◽  
Low Level ◽  
Her 2

An accurate evaluation of theHer-2status has important prognostic and therapeutic implications in many carcinomas. The aim of the study was to correlateHer-2locus (17q11.2) amplification and chromosome 17 gains as assessed by fluorescent in situ hybridization (FISH) with Her-2 protein overexpression by immunohistochemistry (IHC) in patients with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). We analyzed 34 patients withHer-2amplification and/or chromosome 17gains using FISH on brush cytology specimens. Seven patients (21%) showed highHer-2locus amplification (Her-2: Cep17≥5 : 1), 5 (15%) showed lowHer-2locus amplification (Her-2: Cep17≥2<5 : 1), and 22 (65%) displayed gains of chromosome 17 only. Further, we confirmedHer-2amplification on corresponding biopsies that were taken at the same occasion as the cytologybrushings. Then, we compared the FISH results with IHC data obtained from the corresponding biopsies and showed that low level of Her-2 amplification does not correlate with Her-2 protein overexpression (score+3/+2;P=1), in contrast to the high amplification level (P=.001). Thus, in our population of BE and EAC patients, low level ofHer-2amplification does not result in detectable level of Her-2 protein as assessed by IHC.

The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma

Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2562-2567 ◽  
Author(s):  
Rafael Fonseca ◽  
Carina S. Debes-Marun ◽  
Elisa B. Picken ◽  
Gordon W. Dewald ◽  
Sandra C. Bryant ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
Heavy Chain ◽  
Dna Content ◽  
Mayo Clinic ◽  
Fluorescent In Situ Hybridization ◽  
Eastern Cooperative Oncology Group ◽  
Oncology Group

Abstract Aneuploid is ubiquitous in multiple myeloma (MM), and 4 cytogenetic subcategories are recognized: hypodiploid (associated with a shorter survival), pseudodiploid, hyperdiploid, and near-tetraploid MM. The hypodiploid, pseudodiploid, and near-tetraploid karyotypes can be referred to as the nonhyperdiploid MM. Immunoglobulin heavy-chain (IgH) translocations are seen in 60% of patients. We studied the relation between aneuploidy and IgH translocations in MM. Eighty patients with MM and abnormal metaphases were studied by means of interphase fluorescent in situ hybridization (FISH) to detect IgH translocations. We also studied a second cohort of 199 patients (Eastern Cooperative Oncology Group [ECOG]) for IgH translocations, chromosome 13 monosomy/deletions (Δ13), and ploidy by DNA content. Mayo Clinic patients with abnormal karyotypes and FISH-detected IgH translocation were more likely to be nonhyperdiploid (89% versus 39%, P &lt; .0001). Remarkably, 88% of tested patients with hypodiploidy (16 of 18) and 90% of tested patients with tetraploidy (9 of 10) had an IgH translocation. ECOG patients with IgH translocations were more likely to have nonhyperdiploid MM by DNA content (68% versus 21%, P &lt; .001). This association was seen predominantly in patients with recurrent chromosome partners to the IgH translocation (11q13, 4p16, and 16q23). The classification of MM into hyperdiploidy and nonhyperdiploidy is dictated largely by the recurrent (primary) IgH translocations in the latter. (Blood. 2003;102:2562-2567)

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