TÁC ĐỘNG CỦA THỜI GIAN THIẾU MÁU LẠNH ĐẾN BIỂU HIỆN CỦA DẤU ẤN HER2 TRONG UNG THƯ VÚ

Abstract

Background: HER2 (ERBB2) is a receptor tyrosine kinase expressed on the tumor cell membrane and is the therapeutic target of multiple anti-HER2 agents. As a membrane antigen, HER2 immunoreactivity is highly susceptible to pre-analytical variables, particularly cold ischemia time (CIT). Prolonged CIT can induce membrane injury, protein degradation and epitope masking, leading to loss of membranous continuity, attenuation of staining intensity, and inaccurate IHC readouts, with direct implications for treatment selection. Objectives: To assess the impact of CIT on HER2 expression in breast carcinoma by immunohistochemistry (IHC). Subjects and Methods: Exploratory study with purposive sampling. Tumor tissue was grossed into ~3-mm slices and placed into 10% neutral buffered formalin (10% NBF; ~4% formaldehyde, phosphate buffer, pH 7.0) at six CIT points: <1 h, 2 h, 3 h, 4 h, 6 h, and 8 h. Specimens were then fixed for 8–32 h, processed routinely, sectioned at 3–4 µm, stained for HER2 IHC, and scored per ASCO/CAP criteria (0/1+/2+/3+). Endpoints included staining intensity, percentage of HER2-positive tumor cells, and the proportion of tumor cells with discontinuous/indistinct membranous staining (“membrane disruption”). Results: In HER2 (3+) cases, no decline in staining intensity was observed between the earliest and latest CIT points. In HER2 (2+) cases, some shifted to HER2 (1+) with prolonged CIT; no case demonstrated complete loss of expression. The percent positivity and rate of membrane disruption fluctuated slightly but without a consistent linear trend across the <1–8 h CIT window. Conclusions: Under these study conditions, HER2 (3+) immunoreactivity appears relatively stable despite CIT extension, whereas borderline HER2 (2+) cases are more vulnerable to attenuation of membranous staining, risking under-calling (with potential implications for HER2-low categorization and therapy). Strict adherence to ASCO/CAP pre-analytical recommendations – CIT ≤  1 hour, gross slice thickness 2–3 mm, and standardized fixation – is essential to preserve membrane epitopes and ensure reliable HER2 IHC interpretation.