The level of HER-2/neu gene amplification may correlate with some relevant histopathological features of early stage breast cancer. D. Bettio¹, G. Gullo², G. Masci², A. Venci¹, L. Di Tommaso³, A. Santoro². 1) Cytogenetic Laboratory, Humanitas Clinical Inst, Milan, Italy; 2) Oncology Dept.,Humanitas Clinical Inst, Milan, Italy; 3) Anatomic Pathology Laboratory,Humanitas Clinical Inst, Milan, Italy.
   BACKGROUND HER-2/neu gene amplification and/or protein overexpression predict poor outcome in invasive breast cancer and have become crucial determinants in therapeutic decisions. FISH by means of the PathVysion kit was used to investigate HER-2 gene amplification in order to identify different categories of patients with different levels of amplification and correlate this value with histopathological features rather than IHC evaluation of the protein overexpression and looking for a prognostic role of these parameters. METHODS Our study was performed on 28 early stage breast cancer female patients treated with curative surgery randomly taken from the archives of Pathology. Patient characteristics were: median age: 55 (range: 36-73); invasive ductal carcinoma: 24 (86%), invasive lobular: 3 (11%); mixed (ductal and lobular) type: 1 (3%). RESULTS Seventeen patients showed HER-2 amplification with HER-2/CEP17 ratio ranging from 2.1-8.5, whereas 11 FISH negative patients represented the control group. Patients positive by FISH were divided into two groups according to the HER-2/CEP17 ratio: low-level HER-2 amplification (HER-2/CEP17 ratio 2.1-3.9) and high-level HER2 amplification (ratio 4-8). Relevant histopathologic features of tumors in the three groups, no amplification/low-amplification/high-amplification, respectively, were as follows: high histologic grade (G3): 36/33/63% (p 0.07 Mantel-Haentzel test); vascular invasion present: 45/44/75%, high proliferative MIB-1 index (MIB-1 protein 20%): 27/44/63%. No significant difference was observed for ER and/or progesterone-receptor status. On follow-up ranging from 6 to 40 months the worst clinical outcome was among the group with amplification and chromosome 17 polisomy. CONCLUSIONS This is the first observation of a possible correlation between the level of HER-2 amplification and some relevant histopathological features of breast cancer.