Cold ischemia time and formalin fixation time in endometrial cancer: Should breast cancer guidelines for preanalytical variables be applied to hysterectomy specimens?

Objectives: The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) recommend cold ischemia time (cIT) be <60 min, and formalin fixation time (FFT) 6-72 h, to optimize immunohistochemistry (IHC) based on breast cancer data. We assessed whether cIT and FFT impact IHC in endometrial cancer (EC), and determined which factors affect cIT and FFT.

Methods: Surgical EC cases from 2019 to 2023 were reviewed. cIT was calculated by subtracting time of tissue devascularization intra-operatively from time the specimen was placed in formalin. Demographics, clinicopathologic and peri-operative factors, and IHC for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and mismatch repair (MMR) proteins were compared between patients with cIT <60 min versus ≥60 min (prolonged), and compliant FFT (6-72 h) versus non-compliant FFT (<6 or > 72 h). Categorical variables were compared using χ² tests.

Results: 941 patients were included in the analysis. Median cIT was 33 min. Prolonged cIT occurred in 95 (10 %) cases. African American/Black race (p < 0.001), advanced stage (p < 0.001), mini-laparotomy (p < 0.001), performance of surgical procedures beyond standard EC staging (p < 0.001), longer surgical length (p < 0.001), and increased uterine weight (p < 0.001) were independently associated with prolonged cIT. There were no significant differences in ER, PR, HER2, or MMR protein expression based on cIT or FFT.

Conclusion: Prolonged cIT was not associated with differences in biomarker expression via IHC at time of surgical staging for EC. Despite variability in cIT, which is largely due to non-modifiable factors, tumor molecular features remain consistent and can reliably be utilized for prognostic and therapeutic decision-making.