Variability in Her2neu Testing: Validation Study in Search of Economic Solution for India
Trupti Pai, Tanuja Shet, Asawari Patil, Sangeeta Desai. Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
Background: The two FDA approved antibodies Hercep from DAKO and Ventana Her2neu are expensive as screening method for Her2neu evaluation in breast cancer patients in institutes across India. As no EQAS exists there is a need to validate locally available inexpensive antibodies before their generic use.
Design: This is a retrospective study of 206 invasive breast carcinoma cases in which HER2 testing was done by using 6 different anti-HER2 antibodies on immunohistochemistry(IHC) and results were interpreted by three specialist breast pathologists and compared to FISH as a gold standard.
Results: Comparison of HER2 status by IHC using 6 different antibodies, US FDA approved HercepTest had the highest sensitivity, specificity, positive and negative predictive values with lowest false positive (11.7%) and false negative (1%) rates. Considering only Score 3+ as positive, concordance rates with FISH were Hercep (93.29%) >Pathway Ventana (90.6%) >Biocare (89.5%) >NCL CB11 (89.4%) >Biogenex (89.13%) >Dako A0485 (88.6%). With all six antibodies, absence of staining was highly predictive of non-amplified cases (NPV in the range of 92.2%-98.7%) and strong, complete membrane staining was highly predictive of amplified cases (PPV in the range of 84.9%-88.8%). Among the six antibodies, highest concordance of HercepTest was seen with Dako Cerb2 - A0485 (Kappa value 0.82) and lowest concordance was seen with Biocare Cerb2 antibody (Kappa value 0.76). There was almost perfect agreement between Hercep, Dako A0485, Biogenex antibodies and substantial agreement between antibodies Biocare, NCL CB11 and Pathway Ventana. Substantial agreement was noted among the three pathologists for IHC interpretation (kappa value: 0.6-0.79). Pathologists involved in both, routine IHC and FISH reporting of HER2 detection had maximum agreement especially with Pathway Ventana antibody. Apparent causes of inter-observer variations in IHC interpretation in the present study are cytoplasmic staining with membrane accentuation, mimicking the membrane positivity, edge artifact especially in biopsy samples, poor fixation and technical processing and heterogeneity of staining.
Conclusions: We conclude theranostic IHC viz. HER2 which has implication for targeted therapy in breast cancer needs to be performed with clinically validated kits along with stringent quality control. Thus there is no economical solution for Her2neu testing and none of cheaper antibodies compred as well as the FDA approved antibodies.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 37, Tuesday Afternoon