Our experience with HER2 screening of the bioptic breast cancer samples using the method fluorescence in situ hybridization in the year 2014 - application of the updated ASCO/CAP guideline recommendations

Background: The criteria of human epidermal growth factor receptor (HER2) testing and analysing in breast cancer using in situ hybridization were updated by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) in 2013. This new testing criteria define HER2 positive status when there is HER2/CEP17 ratio >2.0 or average HER2 copy number ≥6.0 signals/cell – in these cases the patients unequivocally meet the criteria of HER2 positivity and are suitable for the anti-HER2 targeted therapy. But there is also a group of patients with HER2/CEP17 ratio <2.0 and average HER2 copy number ranging between 4.0–6.0 signals/cell at the same time. This group represents equivocal category, because in these cases it is hard to determine true polysomy 17 from the coamplification of the two adjacent regions – centromeric region of chromosome 17 and gene HER2 (17q12). According to the new guideline recommendations it is necessary to perform reflex testing using a different control DNA probe for chromosome 17.

Material and Methods: 582 samples of paraffin embedded breast cancer tissue were analysed in our laboratory during the period from January 2014 to January 2015. Kreatech^® ON ERBB2, HER2/neu (17q12/SE17) and Cytocell^® Smith-Magenis Chromosome Region (SMCR) and Miller-Dieker (MDS) probes were used for the fluorescence in situ hybridization.

Results: 414 (71.1%) samples were negative with the HER2/CEP17 ratio <2.0 and with the average HER2 copy number <4.0 signals/cell at the same time. In 147 (25.3%) samples was the HER2/CEP17 ratio ≥2.0. These patients unequivocally met the criteria of HER2 positivity. Also 14 (2.4%) samples with the average HER2 copy number ≥6.0 signals/cell met this criteria according to the new guideline recommendations. In 7 (1.2%) samples was the average HER2 copy number of signals/cell ranging between 4.0–6.0 and so in the accordance with the Update Committee recommendations we performed reflex testing using different control probe – FISH probe for regions 17p11.2 (SMCR) and 17p13.3 (MDS). In 6 (1%) of these samples was a polysomy 17 confirmed and so these samples didn't meet the criteria of HER2 positivity. In one sample (0.2%) was the HER2/SMCR ratio 2.4 and it met the criteria of HER2 positivity.

Conclusions: The application of new ASCO/CAP guideline recommendations improves the options of anti-HER2 targeted therapy also for patients, who couldn't benefit from the treatment in the preceding years (in our group of patients it refers to 2.6% patients).

No conflict of interest.