Changing Frequency of Equivocal HER2/Neu Scores and Factors Predictive of Negative HER2/Neu Fluorescent In-Situ Hybridization in Invasive Carcinomas of the Breast
Fouad I Boulos, Cleo J Youssef Massad, Faysal A Fedda, Chantal G Farra, Ehab M Saad Aldin, Hassan Doumiati, Ayman N Tawil, Arafat Tfayli. American University of Beirut Medical Center, Beirut, Lebanon
Background: Since the introduction of HER2 FISH testing to the pathology laboratory at the American University of Beirut Medical Center, a notable increase in the percentage of HER2 immunohistochemistry (IHC) equivocal (2+) cases was recorded (24 to 46%). This was initially attributed to a greater tendency for pathologists to default to FISH testing in cases that were not extremes of positivity and negativity. A closer look at these cases was however deemed necessary, to ensure and maximize consistency as a first endpoint, and as a second endpoint, to identify predictors of FISH negativity in tumors with equivocal IHC. This is especially relevant in the Lebanese patient population which comprises a significant number of self-payers with limited financial resources.
Design: Beginning in January 2010, 73 cases with a score of HER2 2+, HER2 FISH testing and full available clinicopathologic information were reviewed. HER2 IHC score was reassessed by FB and FF. Variables including age, site, size, grade (proliferation rate, pleomorphism and tubule formation), lymphovascular invasion, lymph node involvement, estrogen and progesterone receptor, and HER2 staining in normal glands were recorded. Univariate and multivariate regression analysis was performed to identify statistically significant associations between different variables and HER2 FISH status.
Results: Of the 73 cases blindly reviewed, 13 were downgraded to 1+, and 4 were upgraded to 3+. This resulted in a drop from 47% to 33% in the overall percentage of HER2 2+ cases. There was no FISH HER2 amplification in the downgraded cases. Of the 4 cases that were upgraded, one was not FISH amplified. Analysis of the remaining 56 cases showed the following: 20% (11/56) were FISH amplified, all 14 cases that were grade 1 were FISH negative (p=0.014), only 1 of 14 cases with low proliferation was FISH amplified (p=0.012). This case was 3 mm in size. Finally, none of the 4 cases with strong diffuse positivity for ER and PR in all tumor cells was positive by FISH (p=0.028). Of note is that 10 cases with strong (equivalent to 2+) staining in normal glands were all negative by FISH (p=0.001).
Conclusions: In order to decrease the number of potentially unnecessary FISH tests, we suggest review of the HER2 IHC by at least two pathologists to increase scoring accuracy. Also, in cases where cost may be a problem, FISH testing may not be necessary in cases that are grade 1, have strong diffuse ER and PR staining, or show strong non-specific staining in normal breast epithelium.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 44, Wednesday Morning