HER-2/neu amplification and overexpression in fine needle aspirates from primary breast cancer

C. Bozzetti, Ph.D.,a R. Nizzoli, Ph.D.,a A. Guazzi, Ph.D.,a M. Flora, Ph.D.,b C. Bassano, Ph.D.,b P. Crafa, M.D.,c N. Naldi, Ph.D.,a S. Cascinu, M.D.,a

a Medical Oncology and c Pathology, University Hospital, Parma, Italy; b Department of Pathology, Santa Maria Nuova Hospital, Reggio Emilia, Italy

Aim: There has been an increasing interest in the use of HER-2/neu gene amplification or protein overexpression in breast cancer patients, both for predicting prognosis and planning treatment with chemotherapy, hormone therapy and antibodies against HER-2/neu domain (Herceptin). The possibility of determining HER-2/neu status not only on histologic samples but also on cytologic specimens may help in the treatment decision. Our aim was to evaluate the reliability of HER-2/neu determination by fluorescence in situ hybridization (FISH) on fine needle aspirates (FNAs) from primary breast cancer patients by comparison with the results obtained by FISH and immunohistochemistry (IHC) on the corresponding histologic sections. Methods HER-2/neu amplification was determined by FISH on 66 breast cancer FNAs. Twenty-three and 36 corresponding formalin-fixed, paraffin-embedded sections were assayed by FISH and by IHC respectively, in order to detect HER-2/neu amplification and HER2/neu protein expression. Results Twenty seven percent (18/66) of breast cancer FNAs resulted amplified by FISH. Paired results by FISH cytology and FISH histology were available in 22 cases. Concordance was 91% (20/22). Paired results by FISH cytology and IHC were available in 36 cases. Concordance was 92% (33/36). Eighteen out of the 66 breast cancer FNAs were also submitted to flow cytometric DNA analysis. All diploid cases resulted unamplified by FISH. Six out of the eight aneuploid cases were amplified and 2 were polysomic. Conclusions Our data suggest that FISH may be a reliable procedure for HER-2/neu assessment on cytologic specimens. This may be of particular relevance for patients candidate to preoperative chemotherapy. Moreover, FISH on FNAs from metastatic sites may allow for the determination of HER-2/neu status and the subsequent decision about the use or not of Herceptin.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Gene Expression, Part 2.