The Effect of Cold Ischemia Time and/or Formalin Fixation on Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor-2 Results in Breast Carcinoma.
Author(s): Pekmezci M, Szpaderska A, Osipo C, Ersahin C
Publication: Patholog Res Int, 2012, Vol. 2012, Page 947041
PubMed ID: 22482085 PubMed Review Paper? No
Purpose of Paper
The purpose of this study was to determine if the method of specimen acquisition can influence estrogen receptor (ER) and progesterone receptor (PR) status, as determined by immunohistochemistry, in breast cancer specimens.
Conclusion of Paper
Discordance in hormone receptor status was observed between case-matched biopsies and surgically resected breast cancer specimens in 3% and 11% of cases for ER and PR, respectively. False-negative rates of surgically resected specimens were calculated as 10.9% for ER status and 14.1% for PR status (P<0.001), which the authors note is clinically relevant. Negative ER and PR statuses were confirmed for all cases in a second study. Mean Allred scores for ER were also significantly higher among biopsy than surgically resected specimens (6.1 vs. 5.9; P=0.004), while differences in PR staining were not significant. While specific times were not reported, the authors acknowledged that surgically resected specimens were subjected to longer cold ischemia times, which may have contributed to the observed differences between acquisition methods. Fixation time may also be a confounding factor, as it differed significantly between PR-positive and -negative groups of surgically resected specimens (P=0.022).
Studies
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Study Purpose
The purpose of this study was to determine if the method of specimen acquisition can alter diagnostic results of breast cancer biospecimens. ER and PR status were retrospectively examined among case-matched core needle biopsy and surgically resected specimens procured during lumpectomy or mastectomy for 190 patients. The time between biopsy and surgical resection was not provided. Mean fixation time was 8.7 h for biopsy and 22.2 h for resected specimens. Although cold ischemia time was not recorded, the authors note that biopsy specimens were subjected to less than 1 h of cold ischemia, while surgically resected specimens were subjected to more than 1 h of cold ischemia.
Summary of Findings:
Of the 149 specimens that were evaluated for ER status by immunohistochemistry, 5 specimens (3.4%) produced discordant ER findings between case-matched biopsy and surgically resected specimens; for all 5 cases the biopsy result was ER-positive while the surgically resected specimen was ER-negative. Of the 186 specimens that were evaluated for PR status by immunohistochemistry, 14 specimens (11.1%) produced discordant PR findings between case-matched biopsy and surgically resected specimens. In 5 cases (3.9%), the biopsy was PR-negative and the resected specimen was PR-positive, while the opposite was true in the remaining 9 cases (7.1%). The authors note that negative ER and PR statuses were confirmed for all cases in a second study. False-negative rates of surgically resected specimens were calculated as 10.9% for ER status and 14.1% for PR status (P<0.001), which the authors note as clinically relevant. Mean Allred scores for ER were also significantly higher among biopsy than surgically resected specimens (6.1 vs. 5.9; P=0.004), while differences in PR staining were not significant. When specimens were grouped by acquisition method and hormone receptor status, fixation times were statistically equivalent for ER- positive and -negative biopsies and surgical resections, and PR-positive and -negative biopsies. However, PR-positive surgical specimens were fixed for a longer duration than PR-negative surgical specimens (25.5 h vs. 21.7 h; P=0.022). No clinically significant discrepancies in HER-2 status were identified using FISH and immunohistochemistry among nineteen case-matched biopsy and surgically resected specimens.
Biospecimens
Preservative Types
- Formalin
Diagnoses:
- Neoplastic - Carcinoma
Platform:
Analyte Technology Platform Protein Immunohistochemistry DNA FISH Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Biospecimen Acquisition Cold ischemia time < 1 h
> 1 h
Biospecimen Preservation Time in fixative 6-34 h
Immunohistochemistry Specific Targeted peptide/protein ER
PR
HER-2
FISH Specific Targeted nucleic acid HER-2
Biospecimen Acquisition Method of tissue acquisition Biopsy
Surgical resection