Fig. 4

Poorly calibrated HER2 assays may give false negative and false positive results leading to erroneous patient treatment. Serial sections of a tissue micro array with cores from three breast ductal adenocarcinomas, marked 1, 2 and 3, stained in three laboratories marked A, B and C. Core 1 (upper row): Carcinoma without HER2 gene amplification by FISH test and a 0/1+ immunostaining in labs A and B, while lab C obtains a 3+ staining. Lab C would not do a FISH test, and the patient would be offered an ineffective but costly and potentially hazardous HER2 targeted therapy. Core 2 (middle row): Carcinoma with a low but significant HER2 gene amplification obtained 2+ immunoreaction in lab A. Lab B obtained a 1+ staining which is false negative and the patient would not be offered HER2 targeted therapy in spite of the HER2 gene amplification. Lab C obtained a 3+ staining but in this case it would not influence the treatment. Core 3 (lower row): Carcinoma with high HER2 gene amplification and a 3+ immunoreaction obtained in lab A and C, while lab B obtained a 2+ staining. In a diagnostic setting this tumor would in lab 2 be reflexed to FISH test for final HER2 status, increasing costs and turnaround time. The assay in lab A (reference lab) was based on an FDA approved kit, while the assays in lab B and C were laboratory developed (Courtesy of Mogens Vyberg)