Publication Year: 2000 Visited: 143

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Effective HER-2/neu Diagnosis in Breast Cancer by a Combination of Immunohistochemistry and FISH. Helmut Buehler, Nikola Bangemann, Katja Evers, Christian Becker, Gerhard Schaller, Univ Hosp Benjamin Franklin, Berlin, Germany; Harvard Medical Sch, Boston, MA.

The introduction of Herceptin, a humanized antibody against the HER2 receptor, marked the beginning of a new treatment concept in breast cancer. Since the effectiveness of Herceptin is restricted to HER2-positive tumors the reliable diagnosis of HER2 levels is a prerequisite for successful therapy. Among all diagnostic techniques immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) turned out to be practicable. Both methods have their advantages but also their pitfalls. IHC is cheap and easy to perform but influenced by the pretreatment of the tumor material. FISH is very reliable but a demanding and expensive technique. To reduce the disadvantages we compared the results of both methods and evolved a two step diagnosis for the indication of Herceptin treatment. Thus far 142 patients were examined with both methods. The overexpression of the HER2-protein was quantified with the HercepTest (DAKO), the amplification of the gene with the Inform-kit (Ventana). The results of both methods were consistent for an IHC score of 0, +1 and +3 but differed markedly at +2. In all 44 cases with IHC 0 and +1 no gene amplification could be detected. All 26 cases with +3 were amplified. Out of 72 cases with +2 we found 50 not amplified, 10 moderately amplified ( < 10 gene copies) and 12 highly amplified. From these results we deduced the following proceeding: all tumors are analyzed by IHC. Herceptin treatment is indicated for a score of +3. Then FISH is performed additionally for a score of +2. All patients with gene amplifications > 10 also receive Herceptin. Overall, 27% of the patients (38 out of 142) were positive in terms of the therapy. This diagnostic selection seems to be very effective: 63 out of 100 treated patients responded either with a steady state of the disease or with partial or complete remission.