‘Non-classical’ HER2 FISH results in breast cancer: a multi-institutional study

Morgan Ballard, Florencia Jalikis, Gregor Krings, Rodney A. Schmidt, Yunn Yi Chen, Mara H. Rendi, Suzanne M. Dintzis, Kristin C. Jensen, Robert B. West, Richard K. Sibley, Megan Troxell, Kimberly H. Allison

Research output: Contribution to journalArticle

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Abstract

The 2013 CAP/ASCO HER2 Testing Guidelines Update modified HER2 FISH categories such that some cases with ‘monosomy’, ‘co-amplification/polysomy’, low-level increased HER2 signals or clustered heterogeneity now are considered amplified or equivocal. This study examines the frequency and clinico-pathologic characteristics of breast cancers with equivocal or ‘non-classical’ HER2 FISH results. Breast cancers (2001–2014) with HER2 FISH results, HER2 immunohistochemistry, ER, grade, and age from three institutions (Stanford, UCSF, UWMC) were collected. HER2 FISH was interpreted using the updated recommendations. Amplified cases with non-classical results were grouped into the following categories: (1) ‘monosomy’ (ratio ≥2.0, mean HER2/cell<4.0); (2) ‘co-amplified’ (ratio<2.0, mean HER2/cell ≥6.0); (3) ‘low amplified’ (ratio ≥2.0, mean HER2/cell 4.0–5.9). Heterogeneous cases with clustered HER2-positive cells were also included. Of 8068 cases, 5.2% were equivocal and 4.6% had a ‘non-classical’ HER2 amplified result; 1.4% ‘monosomy', 0.8% ‘co-amplified', 2.1% ‘low amplified’, and 0.3% clustered heterogeneity. These cancers had a high frequency of ER positive (80.4%), Nottingham grade 3 (52.1%) results. The highest percentage of grade 3 cancers (66.7%) and positive HER2 immunohistochemistry (31.7%) was in the ‘co-amplified’ group. The ‘monosomy’ group had the highest percent grade 1 cancers (13.3%) and was most frequently HER2 immunohistochemistry negative (30.1%). Equivocal cases had very similar characteristics to the ‘low-amplified’ category. Cases with non-classical HER2 amplification or equivocal results are typically ER positive, higher grade cancers. ‘Co-amplified’ cases have the highest frequencies of aggressive characteristics and ‘monosomy’ cases the highest frequencies of lower risk features. With little clinical outcomes data currently available on these non-classical HER2 results, these results support the current classification scheme for HER2 FISH, with case-by-case correlation with additional clinical-pathologic factors when evaluating whether to offer HER2-targeted therapies in these non-classical cases.Modern Pathology advance online publication, 14 October 2016; doi:10.1038/modpathol.2016.175.

Original languageEnglish (US)
JournalModern Pathology
DOIs
StateAccepted/In press - Oct 14 2016

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Monosomy
Breast Neoplasms
Immunohistochemistry
Neoplasms
Publications
Guidelines
Pathology

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Ballard, M., Jalikis, F., Krings, G., Schmidt, R. A., Chen, Y. Y., Rendi, M. H., ... Allison, K. H. (Accepted/In press). ‘Non-classical’ HER2 FISH results in breast cancer: a multi-institutional study. Modern Pathology. https://doi.org/10.1038/modpathol.2016.175

‘Non-classical’ HER2 FISH results in breast cancer : a multi-institutional study. / Ballard, Morgan; Jalikis, Florencia; Krings, Gregor; Schmidt, Rodney A.; Chen, Yunn Yi; Rendi, Mara H.; Dintzis, Suzanne M.; Jensen, Kristin C.; West, Robert B.; Sibley, Richard K.; Troxell, Megan; Allison, Kimberly H.

In: Modern Pathology, 14.10.2016.

Research output: Contribution to journalArticle

Ballard, M, Jalikis, F, Krings, G, Schmidt, RA, Chen, YY, Rendi, MH, Dintzis, SM, Jensen, KC, West, RB, Sibley, RK, Troxell, M & Allison, KH 2016, '‘Non-classical’ HER2 FISH results in breast cancer: a multi-institutional study', Modern Pathology. https://doi.org/10.1038/modpathol.2016.175
Ballard, Morgan ; Jalikis, Florencia ; Krings, Gregor ; Schmidt, Rodney A. ; Chen, Yunn Yi ; Rendi, Mara H. ; Dintzis, Suzanne M. ; Jensen, Kristin C. ; West, Robert B. ; Sibley, Richard K. ; Troxell, Megan ; Allison, Kimberly H. / ‘Non-classical’ HER2 FISH results in breast cancer : a multi-institutional study. In: Modern Pathology. 2016.
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abstract = "The 2013 CAP/ASCO HER2 Testing Guidelines Update modified HER2 FISH categories such that some cases with ‘monosomy’, ‘co-amplification/polysomy’, low-level increased HER2 signals or clustered heterogeneity now are considered amplified or equivocal. This study examines the frequency and clinico-pathologic characteristics of breast cancers with equivocal or ‘non-classical’ HER2 FISH results. Breast cancers (2001–2014) with HER2 FISH results, HER2 immunohistochemistry, ER, grade, and age from three institutions (Stanford, UCSF, UWMC) were collected. HER2 FISH was interpreted using the updated recommendations. Amplified cases with non-classical results were grouped into the following categories: (1) ‘monosomy’ (ratio ≥2.0, mean HER2/cell<4.0); (2) ‘co-amplified’ (ratio<2.0, mean HER2/cell ≥6.0); (3) ‘low amplified’ (ratio ≥2.0, mean HER2/cell 4.0–5.9). Heterogeneous cases with clustered HER2-positive cells were also included. Of 8068 cases, 5.2{\%} were equivocal and 4.6{\%} had a ‘non-classical’ HER2 amplified result; 1.4{\%} ‘monosomy', 0.8{\%} ‘co-amplified', 2.1{\%} ‘low amplified’, and 0.3{\%} clustered heterogeneity. These cancers had a high frequency of ER positive (80.4{\%}), Nottingham grade 3 (52.1{\%}) results. The highest percentage of grade 3 cancers (66.7{\%}) and positive HER2 immunohistochemistry (31.7{\%}) was in the ‘co-amplified’ group. The ‘monosomy’ group had the highest percent grade 1 cancers (13.3{\%}) and was most frequently HER2 immunohistochemistry negative (30.1{\%}). Equivocal cases had very similar characteristics to the ‘low-amplified’ category. Cases with non-classical HER2 amplification or equivocal results are typically ER positive, higher grade cancers. ‘Co-amplified’ cases have the highest frequencies of aggressive characteristics and ‘monosomy’ cases the highest frequencies of lower risk features. With little clinical outcomes data currently available on these non-classical HER2 results, these results support the current classification scheme for HER2 FISH, with case-by-case correlation with additional clinical-pathologic factors when evaluating whether to offer HER2-targeted therapies in these non-classical cases.Modern Pathology advance online publication, 14 October 2016; doi:10.1038/modpathol.2016.175.",
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