The effect of cold ischemic time on the immunohistochemical evaluation of estrogen receptor, progesterone receptor, and HER2 expression in invasive breast carcinoma.
Author(s): Yildiz-Aktas IZ, Dabbs DJ, Bhargava R
Publication: Mod Pathol, 2012, Vol. 25, Page 1098-105
PubMed ID: 22460807 PubMed Review Paper? No
Purpose of Paper
The purpose of this paper was to determine the effects of room temperature or refrigerated cold ischemia on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) staining of core biopsy and resected breast tumor specimens.
Conclusion of Paper
Reduced ER, PR and HER-2 staining was observed in surgically resected specimens exposed to refrigerated or room temperature cold ischemia compared to the core biopsy specimens. Mild reductions in ER, PR and HER-2 staining were first observed after 2 h, 0.5 h, and 3 h, respectively, when stored at room temperature prior to fixation and after 4 h for all three proteins when refrigerated prior to fixation. Importantly, refrigerated or room temperature cold ischemia altered ER and PR positivity for some specimens and resulted in decreased HER-2 score.
Studies
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Study Purpose
The purpose of this study was to determine the effects of room temperature or refrigerated cold ischemia on ER, PR and HER-2 staining of breast tumor specimens. 25 surgical resected breast carcinoma specimens were stored for 0.5-48 h at room temperature or 4°C before formalin fixation for 8-48 h and paraffin embedding. Importantly, the authors do not control for differences in fixation duration. Staining was compared to that in previously stained core biopsies which were subjected to minimal cold ischemia time.
Summary of Findings:
Reduced ER, PR and HER-2 staining was observed in 32%, 24% and 24% of surgically resected specimens, respectively, that were exposed to refrigerated cold ischemia compared to the core biopsy specimens. When surgical specimens were stored at room temperature prior to fixation, ER, PR and HER-2 staining were reduced in 48%, 43% and 48% of specimens, respectively, compared to the biopsy specimens. Importantly, mild reductions in ER, PR and HER-2 staining were first observed at 2 h, 0.5 h, and 3 h, respectively, when stored at room temperature and at 4 h for all three proteins when refrigerated. The mean histologic (H)-scores for ER and PR were not affected by refrigerated cold ischemia, but ER and PR H-scores were significantly reduced in specimens stored for 3 h and 24 h, respectively, at room temperature. Importantly, refrigerated cold ischemia of 4 h resulted in a one-step reduction in HER-2 staining for one specimen, and refrigerated cold ischemia of 24 h resulted in loss of ER positivity for 1 specimen and PR positivity for 1 specimen, and cold ischemia of 48 h resulted in loss of ER positivity for 1 additional specimen and PR positivity for 2 additional specimens. Similarly, room temperature storage altered ER positivity in one specimen at 24 h, altered PR positivity in one case each at 4, 24 and 48 h and resulted in 1-2 step reductions in HER-2 score in 6 specimens (2 at 3 h, 1 at 4 h, 1 at 24 h, and 2 at 48 h).
Biospecimens
Preservative Types
- Formalin
Diagnoses:
- Neoplastic - Carcinoma
Platform:
Analyte Technology Platform Protein Immunohistochemistry Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Biospecimen Acquisition Cold ischemia time 0 h
0.5 h
1 h
2 h
3h
4 h
24 h
48 h
Immunohistochemistry Specific Targeted peptide/protein ER
PR
HER-2
Storage Storage temperature Room temperature
4°C
Biospecimen Acquisition Method of tissue acquisition Biopsy
Surgical resection