Prognostic significance of p34(cdc2) cyclin-dependent kinase and MIB1 overexpression, and HER-2/neu gene amplification detected by fluorescence in situ hybridization in breast cancer

The HER-2/neu oncogene, localized to chromosome 17q, shares substantial hom ology with the epidermal growth factor receptor: HER-2/neu gene amplificati on and protein overexpression have been associated with poor prognosis in b reast cancer Formalin-fixed paraffin-embedded primary invasive breast cance r tissues from 135 women were tested for HER-2/neu gene amplification by au tomated fluorescence in situ hybridization (FISH) using a sequence probe. T he tumors also were evaluated by immunohistochemistry for proliferation mar kers Ki 67 (MIBI) and p34(cdc2) cyclin-dependent kinase. Patients were foll owed up for a mean of 61 months. There were 70 node-negative and 65 node-po sitive cases. Ki 67 and p34(cdc2) proliferation marker overexpression, HER- 2/neu oncogene amplification, large tumor size, high tumor grade, advanced tumor stage, positive lymph node status, and distant metastasis at the rime of diagnosis predicted disease-related death in combined node-negative and node-positive breast cancer. HER-2/neu gene amplification, tumor stage, ly mph node metastasis, tumor grade, and distant metastasis at the time of dia gnosis independently predicted disease outcome. HER-2/neu amplification det ected by FISH also predicted disease-related death independent of lymph nod e status, tumor grade, and distant metastasis in breast cancer patients who received adjuvant therapy.