Hormone Receptor and HER2/Neu Immunohistochemistry in Multifocal/Multicentric Breast Carcinoma
Shannon Covey, Dana D Baker, Siobhan M O'Connor. UNC School of Medicine, Chapel Hill, NC; Duke University, Durham, NC
Background: The prognostic and predictive value of ER/PR/HER2 status in breast cancer is well established. In addition, response to hormone-directed therapy correlates with degree of ER reactivity. A moderate number of breast cancers are multifocal/multicentric (MF/MC) and there is limited data to direct whether more than one focus should be immunostained. The largest and most recent study (65 ductal carcinoma cases) suggests that receptor status may be adequately assessed by analysis of one focus, particularly if foci are histologically similar and low grade. Our goal was to evaluate a larger number of MF/MC cases and to determine if specific histologic features correlate with IHC discrepancies and may be used to guide the decision to stain more than one focus.
Design: MF/MC invasive breast cancer cases from 1/2000 to 5/2011 were identified in CoPath. Reports and archived slides were reviewed to verify number of foci, MF vs MC, grade, and morphology. ER/PR IHC was scored by intensity and percent of cells staining at each intensity. Modified H score was calculated by multiplying intensity x percent tumor cells labeled, range 0 to 300. Qualitatively, tumors were considered ER/PR+ if ≥1% nuclei stained. HER2 IHC was scored using ASCO/CAP guidelines. If IHC was not performed at UNC, different clones were used, or staining not well preserved, tissue blocks were retrieved to perform IHC. Sections were immunostained using BenchMark XT IHC/ISH staining modules with ER (Ventana, SP1), PR (Ventana, 1E2), and HER2 (Ventana, 4B5) antibodies.
Results: A total of 104 cases (225 tumors) were evaluated. ER results were discordant in 4 cases. One of these 4 was multicentric, 3 multifocal. In two cases, foci were morphologically different - in one, foci were the same grade and in the other, different grades. In the remaining two cases, foci were morphologically similar and all high grade (9/9); foci were triple negative except for the weak ER positivity seen in one focus from each case. No positive/negative HER2 discordancies were identified. PR results were more variable.
Conclusions: In the majority of MF/MC breast cancer cases, it is sufficient to immunostain a single focus. In order to assure that a patient is offered appropriate therapeutic options, it may be advisable to stain more than one focus for ER if 1) the index focus is high grade and triple negative or 2) it is ER negative and other foci are morphologically different. MC vs MF and differences in grade (low or intermediate) among foci did not predict discordant IHC.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 48, Tuesday Afternoon