HER2 Status Determined on Pre Operative Biopsies and in Operative Specimens: Concordance among Immunohistochemistry (IHC) Fluorescence In Situ Hybridization (FISH) and Chromogenic In Situ Hybridization (CISH) Techniques in the CRITHER Study
P Roger, B Lannes, A Balaton, C Hayem, F Campana, L Arnould, F Penault-Llorca, G MacGrogan. Hal Lapeyronie, Montpellier, France; Hal Hautepierre, Strasbourg, France; Centre Pathologie, Bivres, France; Roche, Neuilly sur Seine, France; Centre Leclerc, Dijon, France; Centre Perrin, Clermont-Ferrand, France; Inst. Bergoni, Bordeaux, France
Background: In breast cancer, HER2 status is assessed by IHC or FISH on operative tissue sample and In situ hybridization techniques are standard tools for determining equivocal IHC 2+ overexpression and deciding the correct treatment for HER2-positive breast cancer patients. Oncologists sometimes ask for assessment of HER2 status on per cutaneous core biopsy (CB).The objective of the CRITHER study was to investigate concordance between the results of CISH, FISH, and IHC techniques on pre-operative CB samples for HER2 status compared with status determined by FISH on surgical specimen from untreated non-metastatic breast cancer patients in France.
Design: Analysis was performed on samples from 260 patients recruited at 24 pathology centers for the period 2003 to 2006 inclusive. Recruitment was made on the basis of IHC obtained from operative tissue samples in order to obtain around 50% HER2-positive (3+), 30% HER2-negative (0/1+), and 20% HER2-equivocal (2+) cases. CISH and IHC were performed on the pre-operative CB and matched surgical specimen in the participating laboratories, and FISH on both specimens in each of 4 reference pathology centers. IHC staining was analyzed according to different scores.
Results: The rate of discordance between pre-operative CISH and operative FISH was 1.8% with 1.5% false-positives and 2.2% false-negatives (k=0.963; p<0.001); the corresponding rate for pre-operative IHC (excluding IHC 2+ cases) and operative FISH was 1.5% with 1.6% false-positives and 1.4% false-negatives (k=0.953; p<0.001). Comparison of pre-operative and operative samples showed expected low rates of discordance for CISH (0.85%; k=0.982; p<0.001) and FISH (0.45%; k=0.991; p<0.001), with no false positives. Results for the IHC scoring system analyses on concordance will be presented at the meeting.
Conclusions: Concordance for both CISH and FISH between pre-operative and operative results was excellent. There was a high rate of concordance for pre-operative CISH and IHC HER2 status determination on CB (excluding IHC 2+ cases) compared with operative FISH results in patients with previously untreated non-metastatic breast cancer.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 50, Tuesday Morning