The Effects of ASCO/CAP Guidelines on Her2/Neu Reporting: An Analysis of 662 Consecutive Breast Cancer Cases with Emphasis on IHC 2+ and 3+ Cases
PB Illei, C Griffin, H Nassar. The Johns Hopkins Medical Institutions, Baltimore, MD
Background: New guidelines were recently published by ASCO/CAP for evaluating Her2 protein expression and gene amplification in invasive breast carcinoma. By FISH, a Her2/Neu:CEP17 ratio greater than 2.2 is considered a positive result.By immunohistochemistry (IHC), a positive result (3+) is given when there is a complete intense membranous Her-2 labeling in at least 30% of the tumor cells. Prior guidelines (FDA approved) required at least 10% of tumor labeling by IHC to call the tumor Her-2 positive (3+) . The higher percentage of tumor staining by IHC (30% instead of 10%) was recommended based on the experience of the panelists rather than published data.
Design: We have reviewed the Her-2 results of 662 consecutive breast carcinoma cases processed at our institution. The results on all cases were reported according to the ASCO/CAP guidelines. We rescored the cases using the original FDA approved guidelines. We compared the results of the old and the new guidelines with an emphasis on the 2+ and 3+ cases by IHC. FISH results were available on all IHC 2+, the majority of 3+ and a subset of 1+ and 0 cases.
Results: The cases with a score of 0 or 1+ were the same using both guidelines (112 and 295 respectively). Of those, FISH was done on twelve Her2/neu 0+ cases (all FISH negative) and on 44 Her-2/neu 1+ cases (5 borderline, 39 FISH negative). For the IHC 2+ and 3+ cases, the results are summarized in table-1. Fourteen cases that scored as 3+ using the old guidelines were scored as 2+ according to the new guidelines. Of these 14 cases, six were FISH positive, seven were FISH negative and one was borderline.
Table-1: Her-2 IHC scoring using the old and new guidelines
|IHC score||N||FISH +||FISH borderline||FISH -|
Conclusions: Our data shows that 18% of the cases scored as 3+ by IHC using the old guidelines are scored as 2+ using the new ASCO/CAP guidelines. Half of these cases are Her-2 negative by FISH. Therfore the use of a higher cut-off (30% as compared to 10%) for defining the positive 3+ cases by IHC seems to be justified.
Tuesday, March 10, 2009 11:00 AM
Platform Session: Section B, Tuesday Morning