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.