HER2Δ16 expression in HER2-positive breast cancer.

Abstract

31 Background: HER2Δ16 isoform was detected in breast cancer and showed similar increased transforming activity to somatic mutation or deletion activated rat HER2 oncogene with 89% of HER2-positive breast cancer with this mutation developing local lymph node positive disease progression. This is the first study characterizing and determining the prevalence of HER2Δ16 isoform in patients from a NAPBC-accredited cancer center. Methods: 95 HER2-positive breast cancer tissue samples from 2002 to 2008 were obtained from Akron General Medical Center. Total RNA from cancer cells were isolated and RT-PCR was performed using primers to amplify the wild-type HER2 and HER2Δ16 isoform. DNA products from RT-PCR were then loaded in agarose gel electrophoresis with the HER2Δ16 isoform band being shorter compared to the wild type HER2. Results: Preliminary results from our ongoing study showed 39% (12 of 31) of our HER2 samples has HER2Δ16 isoform. Out of the 12 HER2Δ16 isoform samples, 17% are Stage I, 50% are Stage II, 25% are Stage III, and 8% are Stage IV breast cancer at diagnosis. Patient age ranges from 34 to 87, with 50% of the HER2Δ16 isoform patients having lymph–node positive disease at the time of diagnosis. This is in contrast to patients with HER2 wild type for which 26% (5 of 19) are diagnosed with Stage I disease and 42% have lymph node positive disease at the time of diagnosis. Conclusions: Transgenic mice that overexpressed rat HER2 oncogene with small extracellular domain deletion promoted transforming activity of this protein. HER2Δ16 isoform is detected in 39% of HER2 positive breast cancer based on our preliminary results with 50% having lymph node–positive breast cancer on initial diagnosis. Immunohistochemistry and FISH could not distinguish the wild type HER2 from the HER2Δ16 isoform. Further study is recommended for possible prognosticating utility of HER2Δ16 isoform in breast cancer.