Supernumerary ring chromosome 17 identified by fluorescent in situ hybridization

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.

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

Journal of Oncology ◽

10.1155/2010/382582 ◽

2010 ◽

Vol 2010 ◽

pp. 1-8 ◽

Cited By ~ 1

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.

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The Relationship between Numerical Aberrations of Chromosome 17 and Nuclear DNA Content in Colorectal Carcinoma Detected by Fluorescent In Situ Hybridization (FISH) and Cytofluorometry Using Auto-scanning Stage.

ACTA HISTOCHEMICA ET CYTOCHEMICA ◽

10.1267/ahc.30.665 ◽

1997 ◽

Vol 30 (5/6) ◽

pp. 665-673

Author(s):

Kanji Kawai ◽

Shinshichi Hamada ◽

Hisakazu Yamagishi ◽

Hirosumi Itoi ◽

Toshiya Ochiai ◽

...

Keyword(s):

In Situ Hybridization ◽

Colorectal Carcinoma ◽

Dna Content ◽

Fluorescent In Situ Hybridization ◽

Nuclear Dna ◽

Nuclear Dna Content ◽

Chromosome 17 ◽

Numerical Aberrations ◽

The Relationship

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Identification of a small supernumerary ring chromosome 8 by fluorescent in situ hybridization in a child with developmental delay and minor anomalies

American Journal of Medical Genetics ◽

10.1002/ajmg.1320500103 ◽

1994 ◽

Vol 50 (1) ◽

pp. 12-14 ◽

Cited By ~ 17

Author(s):

A. R. Melnyk ◽

G. Dewald

Keyword(s):

In Situ Hybridization ◽

Developmental Delay ◽

Fluorescent In Situ Hybridization ◽

Ring Chromosome ◽

Chromosome 8 ◽

Minor Anomalies

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P1-12-17: Fluorescent In Situ Hybridization Evaluation of HER2 Status in Tumors with Chromosome 17 Polysomy.

10.1158/0008-5472.sabcs11-p1-12-17 ◽

2011 ◽

Author(s):

E Pietri ◽

L Medri ◽

A Farolfi ◽

S Sarti ◽

R Maltoni ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescent In Situ Hybridization ◽

Chromosome 17 ◽

Her2 Status

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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

Journal of Clinical Oncology ◽

10.1200/jco.2015.61.8983 ◽

2016 ◽

Vol 34 (29) ◽

pp. 3502-3510 ◽

Cited By ~ 53

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.

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