Impact of Cold Ischemic Time on Estrogen Receptor, Progesterone Receptor, and HER2 Semi-Quantitative Immunohistochemical Scoring
Isil Z Yildiz-Aktas, David J Dabbs, Rohit Bhargava. University of Pittsburgh Medical Center
Background: There is a dearth of data regarding the acceptable limits of cold ischemic time (CIT) for breast tumors subjected to immunohistochemical(IHC) analysis for ER/PR/HER2. ASCO/CAP guidelines currently recommend a CIT of <1hour.
Design: Breast resection specimens were subjected to variable CIT periods (0.5, 1, 2, 3, 4, 24, and 48 hours) within the refrigerator and at room temperature. Hormone receptors were semi-quantitatively scored using H-score method. HER2 was scored using the ASCO/CAP guidelines. The results were compared to the core biopsy scores which have negligible CIT. Mild reduction in staining for hormone receptors was judged present if the H-score on the resection specimen was between one-half and three-fourth of the H-score at core biopsy. Significant reduction was judged present when the H-score on resection was less than one-half of the core biopsy H-score. Mild reduction in HER2 staining was judged present if there was one step discordance, and significant reduction was judged present if there was 2-step reduction in staining. A true reduction was judged present only when the reduction was consistently present for the increasing time interval. A focal reduction for a particular time sample was attributed to the heterogeneity of the tumor sample.
Results: The study included 26 cases, all of which had refrigerated samples. Non-refrigerated samples (samples at room temperature) were present on 24 cases. The reduction in staining for ER, PR, and HER2 is shown in table 1.
|Mild reduction||Minimum time to mild reduction||Significant reduction||Minimum time to significant reduction|
|Refrigerated Sample ER||8/26 (31%)||4 hours (3 of 8 cases)||6/26 (23%)||4 hours (1 of 6 cases)|
|Non-refrigerated Sample ER||9/24 (38%)||2 hours (1 of 9 cases)||8/24 (33%)||2 hours (1 of 8 cases)|
|Refrigerated Sample PR||6/26 (23%)||0.5 hour (2 of 6 cases)||4/26 (15%)||4 hours (1 of 4 cases)|
|Non-refrigerated Sample PR||8/24 (33%)||0.5 hour (1 of 8 cases)||6/24 (25%)||2 hours (1 of 6 cases)|
|Refrigerated Sample HER2||2/26 (8%)||4 hours (2 of 2 cases)||0/26 (0%)||No significant reduction|
|Non-refrigerated Sample HER2||10/24 (42%)||3 hours (3 of 10 cases)||2/24 (8%)||24 hours (2 of 2 cases)|