Controlling Preanalytic Variables Eliminates Her2 and Estrogen Receptor Status Discordance among 50 Paired Breast and Axillary Node Core Biopsies
Chase Carter, James M Avent, Regina E Rosenthal, M Elizabeth H Hammond, Dylan V Miller. Intermountain Medical Center/LDS Hospital, Salt Lake City, UT
Background: Discrepancy in Her2 and estrogen receptor (ER) status among primary breast tumors and their axillary lymph node metastases has been reported in the range of 6-18%, leading to confusion as to the optimal sample for testing. In these reports, however, the preanalytic conditions (particularly time to fixation and fixation duration) for the samples were either nonuniform or unspecified. Whether the discrepancies are due to innate biologic factors (such as intratumoral heterogeneity) versus assay performance due to differing preanalytic conditions is therefore unclear.
Design: Core biopsy samples from 50 primary breast invasive ductal carcinomas and their corresponding ipsilateral axillary lymph node metastases obtained at the same procedure, using the same core biopsy sampling device, fixed under the same conditions, stained on the same staining runs (Dako HercepTest and ER clone 1D5), and analyzed using digital image analysis constitute the study cohort. Patient demographics and tumor characteristics (from subsequent excision specimens or clinical imaging) were obtained from electronic medical records.
Results: The mean age of the 50 women was 51.72 (27-86). Mean time to fixation was 2.55 minutes and the mean duration of fixation was 12.87 hours (6.4 -29.7). The Her2 scores were 0 = 2, 1+ = 13, 2+ = 12, 3+ = 23. Complete agreement in Her2 scores was seen among all paired samples. For 3+ cases, the mean tumor size was 3.47 cm, 44% were ER negative and the mean tumor grade was 2.61 (of 3). For 0/1+ cases, the mean tumor size was 3.86 cm, 38% were grade 3 and triple negative, and the mean tumor grade was 2.46 with three grade 1 tumors (seen only in this group). The ER (Allred) scores were 0 = 17, 3 = 1, 4 = 1, 5 = 3, 6 = 9, 7 = 7, 8 = 12. For ER negative tumors the mean tumor grade was 2.76. For ER positive tumors the mean tumor grade was 2.39 including all 3 grade 1 tumors. Only minor discrepancies in Allred scores occurred between the paired samples; 5 with a difference of 1 (6-7, 7-8, 8-7, 7-6, 8-7, and one with a difference of 2 (8-6). The mean age did not differ significantly by ER or Her2 status.
Conclusions: Under matched processing conditions, these 50 paired primary breast tumors and their lymph node metastases show congruent Her2 and ER staining results. Minor differences in staining intensity and percent positive cells were noted. It is possible these minor differences, if magnified through the influence of disparate fixation conditions, could account for the higher discrepancy rates reported in the literature.
Monday, March 19, 2012 1:00 PM
Poster Session II # 69, Monday Afternoon