[275] Human Epidermal Growth Factor Receptor 2 (HER2) Status Determination Using Single Color Versus Dual Color Fluorescence In-Situ Hybridization(FISH) Assay: Impact of Monosomy and Polysomy 17

LA Niemeier, D Dabbs, U Surti, K Cieply, J Yu, R Bhargava. University of Pittsburgh, Pittsburgh, PA

Background: The CAP/ASCO guideline is an important document for interpretation of HER2 FISH results. A FISH result of more than 6 HER2 gene copies per nucleus (using single color FISH or S-FISH) or HER2 to chromosome 17 ratio of more than 2.2 (using dual color FISH or D-FISH) are considered positive for HER2 gene amplification. An equivocal result is 4-6 copies of HER2 per cell (S-FISH) or ratio of 1.8 to 2.2 (D-FISH). However, CAP/ASCO guidelines fails to address the discordance that can occur based on the type of probe used (S-FISH versus D-FISH) especially when monosomy or polysomy for chromosome 17 is present.
Design: The current study was performed to determine the impact of monosomy and polysomy 17 in the context of S-FISH and D-FISH. Monosomy 17 was defined as one signal for chromosome enumeration probe 17 (CEP17) in >50% of the examined cells. Polysomy 17 was defined as an average of 3 or more signals for CEP17. The monosomy cases were obtained from our partner institution that performed D-FISH on 53 consultation cases. The 20 polysomy cases were obtained from our previously studied dataset (Mod Pathol. 2009;22 (Supplement 1): Abstract 179). All polysomy cases showed 2+ expression by immunohistochemistry. Although the FISH was performed using dual color probe, the data was analyzed based on HER2 gene signal/cell (S-FISH) versus HER2:CEP17 ratio (D-FISH).

Monosomy Cases (n=53)
SFISH- Not AmplifiedSFISH- EquivocalSFISH- Amplified
DFISH- Not Amplified3000
DFISH- Equivocal000
DFISH- Amplified8*3*12
*Discrepant cases (discrepancy rate is 21%)

Polysomy Cases (n=20)
SFISH- Not AmplifiedSFISH-EquivocalSFISH-Amplified
DFISH- Not Amplified710*3*
DFISH- Equivocal000
DFISH- Amplified000
*Discrepant cases (discrepancy rate is 65%)

Conclusions: Invasive breast cancer cases that have monosomy of chromosome 17, D-FISH overestimates HER2 amplification (21%). In contrast, the cases that demonstrate polysomy 17, S-FISH overestimates HER2 gene amplification (65%). Despite some interpretation challenges associated with D-FISH, we still recommend using dual color probe for HER2 FISH. The CAP/ASCO criteria are suboptimal in interpreting these difficult cases. Until a consensus is reached in interpreting these cases, a pragmatic approach should be undertaken to avoid overestimation of HER2 gene amplification.
Category: Breast

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 29, Monday Morning


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