In the modern era of precision medicine, a number of class II immunohistochemistry (IHC) biomarkers are routinely tested in pathologic laboratories to select cancer patients who may be candidates for hormonal, targeted, and immune therapies. Pre-analytical factors, including tissue processing, are critical components of biomarker testing and require validation to ensure reliable results. In this study, we aimed to study the impact of tissue processing on biomarkers (including ER, PR, HER2, mismatch repair (MMR) proteins, BRAF V600E, and PD-L1) in a large prospective cohort of 109 tumors. We found that ER and MMR were not impacted; PR, HER2, and BRAF V600E were minimally affected; and PD-L1 regardless of the antibody clone was strongly influenced by a combination of tissue processing procedures and intratumoral heterogeneity. Our findings suggest that validation of pre-analytical parameters, such as tissue processing, is important for certain class II biomarkers, in particular PD-L1 IHC.

在现代精密医学时代，许多II类免疫组织化学（IHC）生物标志物在病理实验室中进行常规测试，以选择可能适合激素，靶向和免疫疗法的癌症患者。分析前因素，包括组织处理，是生物标志物测试的关键组成部分，需要进行验证以确保可靠的结果。在这项研究中，我们旨在研究在109个大型前瞻性队列研究中，组织加工对生物标志物（包括ER，PR，HER2，错配修复（MMR）蛋白，BRAF V600E和PD-L1）的影响。我们发现ER和MMR均未受影响。PR，HER2和BRAF V600E受到的影响最小；不论抗体克隆如何，PD-L1和PD-L1都受到组织处理程序和肿瘤内异质性的共同影响。