Impact of Chromosome 17 Polysomy and Equivocal Immunostaining Results on the HER2 Status Determined by Chromogenic In Situ Hybridization: A Study of Two Institutions Using the New ASCO/CAP Scoring Criteria
Y Gong, W Sweet, YJ Duh, L Greenfield, S Trivedi, WF Symmans, J Isola, N Sneige. The University of Texas M. D. Anderson Cancer Center, Houston, TX; Invitrogen Corporation, Camarillo, CA; StatServ Consulting, Inc., Chino Hills, CA; Institute of Medical Technology, University of Tampere, Tampere, Finland
Background: The new ASCO/CAP guidelines mandated that a new HER2 assay should show 95% concordance with another validated assay for positive and negative results before the test is offered. Because CISH defines HER2 status usually based on an absolute HER2 gene copy number, without chromosome 17 corrections, the reliability of CISH on the cases with chromosome 17 polysomy and equivocal IHC is of interest.
Design: Paraffin tissues of 286 breast carcinomas were tested for HER2 status by FISH (Vysis) and IHC (HercepTest) at MD Anderson (site A) and University of Tampere (site B). Cases showing chromosome 17 polysomy or equivocal IHC score were selected to examine the concordance between CISH and FISH at each site and the reproducibility of CISH between two sites. Results were interpreted by pathologists at each site using the new ASCO/CAP scoring criteria.
Results: Polysomy of chromosome 17 was found in 51 cases at site A and 22 cases at site B. The total number of tumors showing polysomy 17 at either or both sites was 66. Using the three-category criterion (amplified, equivocal and non-amplified), the concordance between the two methods was 91.7% at site A and 95.5% at site B, and the intersite agreement on CISH was 90.3%. Using the two-category criterion (i.e., excluding equivocal cases), the concordance between the two methods was 100% at both sites, and the intersite agreement on CISH was 100%. With HercepTest, 36 cases showed equivocal score at site A and 43 cases at site B, 49 cases had equivocal score at either or both sites. Using the three-category criterion, the concordance between the two methods was 85.3% at site A and 87.8% at site B, and the intersite agreement on CISH was 86.7%. Using the two-category criterion, the concordance between the two methods was 96.7% at site A and 97.3% at site B, and the intersite agreement on CISH was 97.4%.
Conclusions: The concordance between CISH and FISH on cases with chromosome 17 polysomy and with equivocal IHC score achieves the high concordance mandated by the ASCO/CAP guidelines, with very high reproducibility of CISH between two sites.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 63, Wednesday Afternoon