HER-2/Neu Overexpression and Amplification in Esophageal Adenocarcinoma and High Grade Dysplasia
Y Hu, D Hicks, T Godfrey, J Peters, D Tan, X Qiu, Z Zhou. University of Rochester Medical Center, Rochester, NY; MD Anderson Cancer Center, Houston, NY
Background: Her-2 oncogene is localized to chromosome 17q and recently is reported to have an amplification in esophageal adenocarcinoma (EAC). Clinical trials using trastuzumab for EAC are performed in several institutes. However, the prevalence and clinical criteria of overexpression and amplification in EAC and its precursor lesions are controversial.
Design: Samples from 116 cases of EAC, 15 high grade dysplasia (HGD), 18 low grade dysplasia (LGD), 34 Barrett's esophagus (BE) without dysplasia, 283 columnar cell change (CCM), and 89 squamous mucosa (SM) within formalin-fixed paraffin-embedded tissue microarray blocks were examined. The tissue microarray was stained by routine practical techniques in our laboratory for breast carcinoma with mouse monoclonal anti-Her-2 antibody (Dako) and CISH (Dako) with adequate positive and negative controls. The percentages (0-100%) and intensities (1-3+) of positive membrane Her-2 staining cells were determined. The ratio between HER2/neu and 17 chromosome copy numbers was counted. The cutoff of the positive overexpression and amplification is ≥ 2.
Results: With the IHC studies, EAC (11, 9.48%) and HGD (1, 6.67%) showed positive membrane Her-2 staining (2-3+). No LGD, BE, CCM and normal SE showed positive overexpression. With the CISH studies, EAC (21, 18.10%) and HGD (1, 6.67%) showed positive amplification (≥2). No LGD, BE, CCM and normal SE (0, 0%) showed positive amplification. All Her-2 overexpression cases (2-3+) with IHC study showed the amplification with CISH study. Five Her2 expression cases (1+) with IHC study also showed the amplification with the CISH study. However, five cases with Her-2 amplification with CISH study show no expression with IHC studies. EAC showed statistically significantly higher overexpression and amplification compared to the LGD, BE, CCM, and normal SM groups.
Conclusions: This study confirms that Her2 is overexpressed and amplified in EAC and HGD with routine practice techniques in our IHC and molecular laboratory. It is negative in LGD, BE, CCM and normal SM. However, the CISH method showed higher sensitivity than the IHC to detect Her-2 change. Clinically, CISH test is recommended for all patients with 1+ Her2 IHC staining. Her2 amplification only in EAC and HGD suggests that the cases with Her2 overexpression or amplification would be a good treatment target for a clinical trial.
Tuesday, March 23, 2010 8:15 AM
Platform Session: Section E, Tuesday Morning