Backgrounds: Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is a critical predictive biomarker for immune checkpoint inhibitor (ICI) therapy in triple-negative breast cancer (TNBC). However, prolonged storage of formalin-fixed paraffin-embedded (FFPE) tissue may reduce antigenicity, potentially leading to false-negative results. False-negative results may lead to the inappropriate selection of ICI therapy. We investigated the effect of FFPE storage duration on PD-L1 immunoreactivity.Methods: We retrospectively analyzed 63 TNBC cases with PD-L1 testing using the 22C3 pharmDx assay at diagnosis and repeated IHC on the same FFPE blocks after varying storage durations (<1, 1–2, 2–3, ≥3 years). PD-L1 positivity was defined as Combined Positive Score (CPS) ≥ 10. Associations with clinicopathologic features, pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC), and survival were evaluated.Results: At diagnosis, 41 patients (65.1%) were PD-L1–positive. In the PD-L1–positive group, decreased staining was observed in 0%, 11%, 13%, and 50% of cases for <1, 1–2, 2–3, and ≥3 years of storage, respectively (p= 0.015). PD-L1 positivity correlated with higher Ki67 and nuclear grade. pCR was achieved in 33% of PD-L1–positive vs. 0% of PD-L1–negative NAC patients (p= 0.0527). Survival analysis showed a non-significant trend toward shorter recurrence-free and overall survival in PD-L1–positive patients.Conclusions: Prolonged FFPE storage, particularly beyond three years, significantly reduces PD-L1 immunoreactivity. Testing on recent specimens is recommended to avoid false-negative results that may impact ICI eligibility.
背景：程序性死亡配体1（PD-L1）免疫组织化学（IHC）检测是三阴性乳腺癌（TNBC）免疫检查点抑制剂（ICI）治疗的关键预测性生物标志物。然而，福尔马林固定石蜡包埋（FFPE）组织的长期储存可能降低抗原性，可能导致假阴性结果。假阴性结果可能导致不恰当的ICI治疗选择。本研究探讨了FFPE组织储存时间对PD-L1免疫反应性的影响。 方法：我们回顾性分析了63例TNBC病例，这些病例在初诊时使用22C3 pharmDx检测法进行了PD-L1检测，并在不同储存时间（<1年、1–2年、2–3年、≥3年）后对同一FFPE组织块重复进行了IHC检测。PD-L1阳性定义为联合阳性分数（CPS）≥10。评估了其与临床病理特征、新辅助化疗（NAC）后病理完全缓解（pCR）以及生存期的相关性。 结果：在初诊时，41例患者（65.1%）为PD-L1阳性。在PD-L1阳性组中，随着储存时间延长（<1年、1–2年、2–3年、≥3年），观察到染色强度下降的比例分别为0%、11%、13%和50%（p=0.015）。PD-L1阳性与较高的Ki67指数和细胞核分级相关。接受NAC的PD-L1阳性患者中pCR率为33%，而PD-L1阴性患者中为0%（p=0.0527）。生存分析显示，PD-L1阳性患者的无复发生存期和总生存期有缩短趋势，但未达到统计学显著性。 结论：FFPE组织长期储存，特别是超过三年，会显著降低PD-L1免疫反应性。建议使用近期标本进行检测，以避免可能影响ICI治疗资格的假阴性结果。
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