Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL.
Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL.
Clin Breast Cancer. 2024 Jun;24(4):e310-e318. doi: 10.1016/j.clbc.2024.02.010. Epub 2024 Feb 16.
PD-L1 immunohistochemistry (IHC) is being used as a predictive marker of the benefit derived from immunotherapy in several cancer types, including breast cancer. However, the insight gleaned of the prognostic and predictive value of PD-L1 status and its correlation with molecular characteristics during breast cancer progression remains limited.
We performed an PD-L1 (22C3) assay in pre-treatment primary and metastatic tumor sections from 33 patients with breast carcinoma, matched for post neoadjuvant chemotherapy (p-NACT). PD-L1 expression was evaluated using 3 scoring methods: immune cell (IC) and tumor cell (TC) with a 1% as the cutoff value, and combined positive scores (CPS) with a 1 as the cutoff value. Twenty-two samples from 11 patients had successful fluorescence in situ hybridization (FISH)-based molecular data available for analysis.
In the 33 pre-treatment primary tumors, PD-L1 IC, TC, and CPS showed positive correlation with stromal tumor infiltrate lymphocytes (sTIL), histological grade 3, and triple negative breast carcinoma (TNBC). In the matched metastatic tumors, only PD-L1 IC showed a positive correlation with sTIL. The primary tumors showed a higher PD-L1 expression than the matched metastatic tumors by IC and CPS. Negative to positive conversion by CPS was identified in the metastatic tumors from lung, pleura and liver. p-NACT tumors also showed a trend of lower PD-L1 expression compared to the pre-treatment tumors. Six patients had matched samples for molecular and PD-L1 comparison, and none of them showed consistent gene alterations or PD-L1 expression among the primary, p-NACT and metastatic tumors.
Our study showed a decrease in PD-L1 expression and disconnected molecular features during breast cancer progression. Repeating PD-L1 IHC testing could be considered in some specific metastatic sites if primary tumors were negative. Further studies are needed to identify other predictive factors for immune checkpoint inhibitor (ICI) therapy in patients with breast carcinoma.
程序性死亡配体 1 免疫组化（IHC）被用作几种癌症类型（包括乳腺癌）免疫治疗获益的预测标志物。然而，PD-L1 状态的预后和预测价值及其与乳腺癌进展过程中分子特征的相关性的深入了解仍然有限。
我们对 33 例乳腺癌患者的新辅助化疗前后原发和转移肿瘤切片进行了 PD-L1（22C3）检测，这些患者进行了配对。使用 3 种评分方法评估 PD-L1 表达：以 1%为截断值的免疫细胞（IC）和肿瘤细胞（TC），以及以 1 为截断值的综合阳性评分（CPS）。11 例患者中有 22 例样本成功获得了用于分析的基于荧光原位杂交（FISH）的分子数据。
在 33 例原发肿瘤中，PD-L1 IC、TC 和 CPS 与间质肿瘤浸润淋巴细胞（sTIL）、组织学 3 级和三阴性乳腺癌（TNBC）呈正相关。在配对的转移肿瘤中，只有 PD-L1 IC 与 sTIL 呈正相关。IC 和 CPS 显示原发肿瘤的 PD-L1 表达高于配对的转移肿瘤。在来自肺、胸膜和肝脏的转移肿瘤中，CPS 检测到阴性到阳性的转换。p-NACT 肿瘤的 PD-L1 表达也较原发肿瘤有下降趋势。6 例患者有匹配的分子和 PD-L1 比较样本，其中原发、p-NACT 和转移肿瘤之间均无一致的基因改变或 PD-L1 表达。
本研究显示在乳腺癌进展过程中 PD-L1 表达下降和分子特征的分离。如果原发肿瘤为阴性，可以考虑在某些特定的转移部位重复 PD-L1 IHC 检测。需要进一步研究以确定乳腺癌患者免疫检查点抑制剂（ICI）治疗的其他预测因子。
