HER2-Positive Breast Carcinomas with Co-amplification or Gain of Chromosome 17 Centromere Locus: Report of Three Cases and an Impact on HER2 Testing

2011 ◽  
Vol 45 (6) ◽  
pp. 665
Author(s):  
Hyeong Chan Shin ◽  
Young Kyung Bae ◽  
Aeri Kim ◽  
Seok Ju Park
Keyword(s):  
Chromosome 17 ◽  
Breast Carcinomas ◽  
Her2 Positive ◽  
Her2 Testing

scholarly journals Outcome of HER2 Testing by FISH applying ASCO/CAP 2007 and 2013 guideline in IHC equivocal group of breast cancer: Experience at tertiary cancer care centre

2017 ◽  
Vol 06 (02) ◽  
pp. 045-046
Author(s):  
Manoj Kumar Panigrahi ◽  
Dushyant Kumar ◽  
Anurag Mehta ◽  
Kandarpa Kumar Saikia
Keyword(s):  
Breast Cancer ◽  
Final Analysis ◽  
Chromosome 17 ◽  
Research Centre ◽  
Her2 Status ◽  
Her2 Positive ◽  
Her2 Testing ◽  
Polysomy 17 ◽  
Cancer Experience ◽  
The Impact

Abstract Background and Objectives: HER2 testing guideline of ASCO/CAP for interpretation and reporting has recently been revised. The study is aimed to measure the impact of 2013 CAP guideline on equivocal HER2 test outcome (immunohistochemistry [IHC] 2+) when tested by fluorescent in situ hybridization (FISH). The study also aims at finding the frequency of polysomy and monosomy of chromosome 17. Materials and Methods: Specimens were collected in Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India. IHC was performed in every case, and FISH was performed in IHC2+ cases. Results: In final analysis includes 557 subjects on the basis of CAP guideline 2007 and CAP guideline 2013. One hundred ninety-two subjects (34.4%) were HER2 amplified according to CAP scoring 2007, and 246 subjects (44%) according to 2013 CAP scoring. Conclusions: FISH results were evaluated (IHC2 + interpreted according to CAP 2007 guideline) with both 2007 and 2013 ASCO/CAP scoring criteria, we identified significantly more HER2 positive cases as compared to cases evaluated using the 2007 criteria (P < 0.05). We also found that in breast carcinoma, HER2 status in the presence of polysomy 17 may vary with the scoring criteria used. Evaluation of FISH result using 2013 ASCO/CAP criteria means that more patients with breast cancer may be appropriate for targeted treatment with trastuzumab, potentially improving their outcome.

scholarly journals Double-Equivocal HER2 Invasive Breast Carcinomas: Institutional Experience and Review of Literature

2018 ◽  
Vol 142 (12) ◽  
pp. 1511-1516 ◽  
Author(s):  
Brannan B. Griffin ◽  
Jennifer L. Pincus ◽  
Kalliopi P. Siziopikou ◽  
Luis Z. Blanco
Keyword(s):  
Chromosome 17 ◽  
Her2 Status ◽  
Breast Carcinomas ◽  
Her2 Positive ◽  
Close Proximity ◽  
Reference Probe ◽  
Institutional Experience ◽  
Reflex Testing ◽  
Invasive Breast Carcinomas ◽  
American Society

Context.— HER2 status is a prognostic factor and therapeutic target in invasive breast carcinomas. Reflex testing using an alternate method is recommended on equivocal cases via immunohistochemistry or fluorescence in situ hybridization (FISH). Therapeutic dilemmas arise when both tests are equivocal. The standard chromosome 17 centromere reference probe (CEP17) is in close proximity to the HER2 locus and may be coamplified, leading to equivocal results. Alternate chromosome 17 reference probes may aid in establishing the true HER2 status. Objective.— To describe our institutional experience using D17S122 probe for reflex FISH testing on double-equivocal invasive breast carcinomas and review the literature on alternate reference probes. Data Sources.— Twenty-two patients with double-equivocal invasive breast carcinomas, defined as HER2 immunohistochemistry score 2+ and FISH equivocal per the 2013 guidelines, were reviewed. Reflex FISH was performed with alternate probe D17S122 and the HER2 status classified for 11 cases by using a revised HER2:D17S122 ratio. Seven of 11 cases (63.6%) were ultimately classified as HER2 positive, while 4 cases (36.4%) remained equivocal. The 7 positive cases showed a HER2:D17S122 greater than 2.0. Conclusions.— Alternate probe D17S122 reclassified more than half of our cases as HER2 positive. Alternate probes may establish true HER2 status and direct proper management, as evidenced by our experience and the literature. Additional investigation is needed to determine which alternate probe(s) is(are) best for reflex testing. Finally, the American Society of Clinical Oncology/College of American Pathologists guidelines may need to be updated to reflect more specific recommendations for the utilization of appropriate probes in double-equivocal HER2 cases.

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.

scholarly journals Abnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vladimir V. Strelnikov ◽  
Ekaterina B. Kuznetsova ◽  
Alexander S. Tanas ◽  
Viktoria V. Rudenko ◽  
Alexey I. Kalinkin ◽  
...  
Keyword(s):  
Cpg Island ◽  
Strong Association ◽  
Cell Activity ◽  
Promoter Hypermethylation ◽  
Normal Breast ◽  
Breast Carcinomas ◽  
Her2 Positive ◽  
A Genome ◽  
Extracellular Matrix Components ◽  
Integrin Α4

AbstractCell transmembrane receptors and extracellular matrix components play a pivotal role in regulating cell activity and providing for the concerted integration of cells in the tissue structures. We have assessed DNA methylation in the promoter regions of eight integrin genes, two nidogen genes, and the dystroglycan gene in normal breast tissues and breast carcinomas (BC). The protein products of these genes interact with the basement membrane proteins LAMA1, LAMA2, and LAMB1; abnormal hypermethylation of the LAMA1, LAMA2, and LAMB1 promoters in BC has been described in our previous publications. In the present study, the frequencies of abnormal promoter hypermethylation in BC were 13% for ITGA1, 31% for ITGA4, 4% for ITGA7, 39% for ITGA9, 38% for NID1, and 41% for NID2. ITGA2, ITGA3, ITGA6, ITGB1, and DAG1 promoters were nonmethylated in normal and BC samples. ITGA4, ITGA9, and NID1 promoter hypermethylation was associated with the HER2 positive tumors, and promoter hypermethylation of ITGA1, ITGA9, NID1 and NID2 was associated with a genome-wide CpG island hypermethylated BC subtype. Given that ITGA4 is not expressed in normal breast, one might suggest that its abnormal promoter hypermethylation in cancer is non-functional and is thus merely a passenger epimutation. Yet, this assumption is not supported by our finding that it is not associated with a hypermethylated BC subtype. ITGA4 acquires expression in a subset of breast carcinomas, and methylation of its promoter may be preventive against expression in some tumors. Strong association of abnormal ITGA4 hypermethylation with the HER2 positive tumors (p = 0.0025) suggests that simultaneous presence of both HER2 and integrin α4 receptors is not beneficial for tumor cells. This may imply HER2 and integrin α4 signaling pathways interactions that are yet to be discovered.

Assessment of HER2 gene status in breast carcinomas with polysomy of chromosome 17

Cancer ◽  
2010 ◽  
Vol 117 (1) ◽  
pp. 48-53 ◽  
Author(s):  
Semir Vranic ◽  
Bryan Teruya ◽  
Susan Repertinger ◽  
Pamela Ulmer ◽  
Jill Hagenkord ◽  
...  
Keyword(s):  
Chromosome 17 ◽  
Breast Carcinomas ◽  
Her2 Gene ◽  
Gene Status

scholarly journals Evaluating the risk–benefit ratio of adjuvant trastuzumab-based therapy for T1a,bN0M0 HER2-positive breast carcinomas

2011 ◽  
Vol 22 (11) ◽  
pp. 2530 ◽  
Author(s):  
M.J. Rodrigues ◽  
L. Albiges-Sauvin ◽  
J. Wassermann ◽  
P.H. Cottu
Keyword(s):  
Breast Carcinomas ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Benefit Ratio

scholarly journals Identification of HER2-positive breast carcinomas as a particular subset with peculiar clinical behaviours

2001 ◽  
Vol 3 (S1) ◽  
Author(s):  
P Casalini ◽  
S Ménard ◽  
A Balsari ◽  
E Tagliabue ◽  
M Campiglio ◽  
...  
Keyword(s):  
Breast Carcinomas ◽  
Her2 Positive

p63 expression is associated with high histological grade, aberrant p53 expression and TP53 mutation in HER2-positive breast carcinoma

2020 ◽  
pp. jclinpath-2020-206643
Author(s):  
Shuangping Guo ◽  
Yingmei Wang ◽  
Joseph Rohr ◽  
Li Shang ◽  
Jing Ma
Keyword(s):  
Breast Carcinoma ◽  
Neoadjuvant Therapy ◽  
Histological Grade ◽  
Clinicopathological Features ◽  
Breast Carcinomas ◽  
Her2 Positive ◽  
P53 Expression ◽  
High Histological Grade ◽  
Younger Age ◽  
Significant Difference

Aimp63, a member of the p53 family, is a myoepithelial cell marker usually expressed in metaplastic breast carcinoma and its expression suggests a myoepithelial phenotype. However, its expression and association with clinicopathological features of human epidermal growth factor receptor 2 (HER 2)-positive breast carcinoma is poorly investigated.Materials and methodsSixty-seven patients with oestrogen receptor-negative and progesterone receptor-negative, HER2-positive breast carcinoma who received anti-HER2-based neoadjuvant±adjuvant therapy was retrospectively analysed.ResultsTwenty cases were p63-positive and 47 cases were p63-negative. The clinicopathological features and tumour responses after neoadjuvant therapy and outcomes were analysed. Among HER2-positive tumours, expression of p63 was significantly associated with younger age (42.5 vs 55.9; p=0.010). Expression of p63 was also significantly associated with histological grade 3 (11/20 (55%) vs 11/47 (23.4%); p=0.012) and negatively associated with grade 2 (9/20 (45%) vs 36/47 (76.6%); p=0.012). Intriguingly, p63-positive breast carcinomas showed significant aberrant p53 expression by immunohistochemistry (16/18 (88.9%) vs 29/47 (61.7%); p=0.03) and of TP53 mutation by Sanger sequencing (15/16 (93.8%) vs 12/22 (54.5%); p=0.009). No significant difference in tumour response after anti-HER2 neoadjuvant therapy nor in survival were found between p63-positive and p63-negative breast carcinomas.ConclusionExpression of p63 in HER2-positive breast carcinoma is significantly associated with younger age, poor differentiation, high histological grade and aberrant expression of p53 and of TP53 mutation. HER2-positive breast carcinoma with a myoepithelial immunophenotype shows distinctive clinicopathological features representing a distinct subtype of HER2-positive breast carcinoma. Further, these findings suggest an interaction between p63 and mutant p53 in the tumorigenesis of HER2-positive breast carcinomas.

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