Diagnosis:
Herceptest (Evaluation of HER-2/NEU Amplification in Breast Cancer)
• When immunostaining breast cancer with the HercepTest kit, invasive carcinoma is scored as “0” (no staining, or fewer than 10% of cells showing any membranous staining), “1+” (faint staining of more than 10% of cells, without staining of the entire membrane), “2+” (weak to moderate staining of the entire membrane circumference of greater than 10% of cells), and “3+”(strong staining of the entire membrane circumference of greater than 10% of cells).
• Factors that can affect this semiquantitative test include delayed fixation, underfixation or overfixation, leading to poor protein preservation.
• Excessive antigen retrieval can cause false-positive results, as can crush artifacts, and even small cracks in the section, as well as retraction artifacts around tumor cells.
• These technical factors lead to discordance with FISH results. Only about 30% to 50% of 2+ cases show gene amplification by FISH in various studies, with occasional 1+ cases being amplified and a small percentage of 3+ cases being nonamplified.
• Although the superior predictive value of FISH for trastuzumab responsiveness might have a biologic basis, technical factors are also significant.
