Clinical Pathology

Prognostic Significance of p34cdc2 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 homology with the epidermal growth factor receptor. HER-2/neu gene amplification and protein overexpression have been associated with poor prognosis in breast cancer. Formalin-fixed paraffin-embedded primary invasive breast cancer tissues from 135 women were tested for HER-2/neu gene amplification by automated fluorescence in situ hybridization (FISH) using a sequence probe. The tumors also were evaluated by immunohistochemistry for proliferation markers Ki 67 (MIB1) and p34cdc2 cyclin-dependent kinase. Patients were followed up for a mean of 61 months. There were 70 node-negative and 65 node-positive cases. Ki 67 and p34cdc2 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 time of diagnosis predicted disease-related death in combined node-negative and node-positive breast cancer. HER-2/neu gene amplification, tumor stage, lymph node metastasis, tumor grade, and distant metastasis at the time of diagnosis independently predicted disease outcome. HER-2/neu amplification detected by FISH also predicted disease-related death independent of lymph node status, tumor grade, and distant metastasis in breast cancer patients who received adjuvant therapy.

Author notes

Funded in part by 2 Pathology Applications Grants from Oncor, Gaithersburg. MD, and Ventana Medical Systems, Tucson, AZ. At the time this study was performed. Dr Jeffrey S. Ross, MD, was Medical Director of Oncor. Dr Ross is currently Medical Director of Ventana Medical Systems.

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