Impact of Warm Ischemia Time on HER2 Expression in Breast Cancer Surgical Specimens

Tissue sample quality control has become increasingly crucial as these samples are integral to basic research and clinical practice, particularly in immunohistochemistry and gene panel testing. Standard PREanalytical Code (SPREC) was developed to standardize pre-analytical processes, including warm ischemia time (WIT), cold ischemia time (CIT), and fixation time (FT), which can influence the surgical specimen quality. This study investigated the impact of WIT, CIT, and FT on estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) expression in breast cancer (BC) surgical specimens.

We enrolled 277 patients with first-time BC who underwent surgery at Kanagawa Cancer Center between May 2018 and April 2019. WIT, CIT, and FT were recorded using SPREC ver. 3.0, and their effects on ER, PgR, and HER2 expression were analyzed using immunohistochemistry. Surgical specimens were compared with preoperative needle biopsy samples from the same tumors to control for WIT, CIT, and FT variability.

The median WIT, CIT, and FT were 23 min, 37 min, and 43 h, respectively. Compliance with the American Society of Clinical Oncology/College of American Pathologists guidelines was 91.7% for CIT and 94.9% for FT. ER and PgR expression in surgical specimens decreased with prolonged CIT and FT, but differences were non-significant. However, HER2 expression increased significantly when WIT exceeded 30 min.

WIT could significantly influence HER2 expression in BC surgical specimens, highlighting the need for meticulous WIT control during BC surgery to ensure accurate HER2 assessment, which is critical for guiding therapeutic decisions.