Abstract P2-10-27: No Discordant Receptor Status Results among 50 Paired Breast and Axillary Metastasis Core Biopsies when Pre-analytic Variation is Controlled.
Authors: Miller DV , Rosenthall RE , Avent JM , Carter CC , Hansen J , Hammond MEH 
Published: August 2014

Background: Discrepancy in Her2, estrogen receptor (ER), and progesterone receptor (PR) status among primary breast tumors and their axillary lymph node metastases has been reported in the range of 6–18%, leading to uncertainty as to the optimal sample for testing. It has been hypothesized this reflects heterogeneity within a given patient's tumor, however the pre-analytic conditions (particularly time to fixation and fixation duration) for samples in these studies were either nonuniform for the sample pairs or else unspecified. Altered tissue antigenicity rather than true biologic alterations in receptor expression may account for some the discrepancy reported in the literature. This study of paired primary and metastatic tumors processed in a uniform fashion attempts to address this issue.

Design: Core biopsy samples from 50 primary 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, and analyzed using digital image analysis comprise the study cohort. Patient demographics and tumor characteristics (from subsequent excision specimens or clinical imaging) were obtained from medical records.

Results: Complete agreement in Her2, ER, and PR scores was seen among all paired samples. 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. 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, the mean tumor grade was 2.46 (38% were grade 3 and triple negative). 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 PR (Allred) scores were 0 = 24, 2 = 3, 3 = 4, 4 = 8, 5 = 2, 6 = 6, 7 = 1. For PR negative tumors the mean tumor grade was 2.75. For PR positive tumors the mean tumor grade was 2.40, including all 3 grade 1 tumors. Only minor discrepancies in Allred scores occurred between the paired samples; 4 with a difference of 1 (3–4, 4–5, 4–5, 6–7); and three with a difference of two (3–5, 4–6, 4–6). The mean age did not differ significantly by any receptor status.

Conclusion: Under matched processing conditions, these 50 paired primary breast tumors and their corresponding lymph node metastases show congruent Her2 and ER staining results. This number of cases should have detected discrepancies in the range of 6–18%. Minor differences in staining intensity and %positive cells were noted, but none resulted in a positive vs negative mismatch. These data suggest the possibility that these minor differences, magnified through the influence of disparate fixation conditions, could account for the higher discrepancy rates reported in the literature.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-27.