Montse Verdú1,2, Marta González1, Ruth Roman1, Natalia Rodón1, Carme Pubill2, Begoña Martínez1,2, Myriam Gorriz2, Beatriz Garcia-Pelaez1, Miquel Calvo4 and Xavier Puig1,2,3.
1BIOPAT. Biopatologia Molecular, SL, Grup Assistència; 2Histopat Laboratoris; 3Hospital de Barcelona SCIAS, Grup Assistència and 4Statistics Department, Universitat de Barcelona. Barcelona, Spain.
Background: The introduction of the ASCO/CAP guidelines in 2007 followed the need to unify methodologies used in HER2 evaluation and to guarantee the predictive test value in the different laboratories. The aim of this study is to review our experience in the assessment of the HER2 status and evaluate the impact of the application of the guidelines in our results.
Design: A cohort of 1386 primary invasive breast cancer formalin-fixed, paraffin-embedded samples, from 2000 to 2010, were prospectively analyzed by immunohistochemistry (IHC) performed by ABC immunoperoxidase staining, using a mouse monoclonal antibody (CB11) and fluorescent “in situ” hybridization (FISH) with chromosome 17 centromeric probe. The IHC results were evaluated following the HercepTest scoring and the FISH results following the manufacture’s recommendations till the implantation of the ASCO/CAP guidelines in 2007.
Results: We observed a decrease in the percentage of positive (14,2 vs 6,7%) and negative (62,4 vs 36,5%) cases by IHC. Nevertheless, using FISH as a gold standard there was an evident improvement in the accuracy of this technique (90,9 vs 97,8%) with an increase in its specificity (91,6 vs 97,8%), sensitivity (87,9 vs 97,7%), positive (71,3 vs 89,6%) and negative (97,0 vs 99,6%) predictive values. The number of equivocal cases also increased considerably (17,2 vs 56,1%). The newly defined FISH equivocal category represents a 5,6% of cases and causes a decrease in the number of positive cases (21,4 vs 16%). Both IHC and FISH results were shown to be significantly dependent on the evaluation method by a loglineal model.
Conclusions: In our experience, the recommendations of ASCO/CAP guidelines significantly increase the number of equivocal results; nevertheless improve the exactitude of the IHC method. Their application decreases the number of positive cases by FISH, and therefore, the indications of specific treatment. The dependency found between IHC and FISH results and the evaluation method should be taken into consideration when assessing the HER2 status.