HER2 Heterogeneity by FISH in Breast Cancers and Matched Lymph Node Metastases: A Pilot Study
Carlos J Suarez, Suzanne M Dintzis, Rodney A Schmidt, Kimberly H Allison. University of Washington, Seattle
Background: In 2009, recommendations for reporting minor populations (5-50%) of cells with HER2 amplification by fluorescence in situ hybridization (FISH) were published (“HER2 heterogeneous cases”). However, there is little data available about the significance of these minor HER2 positive populations. We examined the percentage of HER2 amplified cells by FISH in primary breast cancers and their lymph node metastases.
Design: As a pilot study, FISH for HER2 was performed on 32 cases: 16 primary breast cancers and their matched untreated lymph node metastases. The percent cells with HER2 gene amplification by both HER2:CEP17 ratio and absolute HER2 signals/cell in the primaries was compared to the percent in the LN metastasis.
Results: By the CAP recommended criteria using HER2:CEP17 ratios, 25% (4/16) of primaries and 13% (2/16) of LN metastases had HER2 heterogeneity. By the absolute HER2 signals/cell criteria, 19% (3/16) of cases had heterogeneity in the primary and 0% (0/16) in the matched LN metastases. One case had 0% amplified cells, and no heterogeneity in the primary, but demonstrated HER2 amplification in > 80% of cells in the LN metastasis.
|Heterogeneity by HER2:CEP17 Ratio Criteria||Heterogeneity by absolute HER2 signals/cell criteria|
|Primary||LN Metastasis||Primary||LN Metastasis|
|Overall (N=16)||25% (4)||13% (2)||19% (3)||0% (0)|
|Heterogeneous cases:||% cells with ratio > 2.2||% cells with > 6 HER2 signals/cell|