Researchers led by Martha Wood from Mount Sinai Hospital in Toronto discuss genetic heterogeneity of HER2 status in Modern Pathology. The researchers examined 2,522 breast cancer tumors that were tested for HER2 amplification using fluorescence in situ hybridization. By definition, HER2 amplified tumors have a ratio of HER2 to a chromosome 17 probe that is greater than 2.2. Of those 2,522 cases the researchers studied, 26 percent were genetically heterogeneous. Most of those heterogeneous cases had a non-amplified ratio, 64.5 percent, while 4 percent were amplified. "In conclusion, definitions of 'genetic heterogeneity' in HER2 FISH testing that depend only on the percentage/proportion of amplified cells are not informative of heterogeneity within a tumor population," Wood and her colleagues write. "Rather, the percentage of amplified cells varies with the HER2/CEP17 ratio in a predictable statistical manner. Current definitions of 'genetic heterogeneity' should be reassessed."
Also in Modern Pathology, French researchers evaluate different approaches to determine HER2 status from breast core-needle biopsies. The researchers examined the concordance of HER2 status calls made by immunohistochemistry and silver or chromogenic in situ hybridization on core-needle biopsies with HER2 status determined by fluorescence in situ hybridization on surgical samples, and drew upon 196 cases from 20 histopathological laboratories. "Immunohistochemistry status assessed on cores biopsy is highly concordant with FISH in cores and surgical specimens," the researchers write. "Furthermore, CISH and/or SISH even represents a safe alternative method to determine HER2 status on these cores biopsies to confirm any ambiguous immunohistochemistry results (2+) or to perform HER2 status screening, if ISH is used as first-line screening method." In its paper, the team notes that Roche provided financial support for this work and also managed the study and statistical analysis.