Neoadjuvant chemotherapy (NAC) is now the standard of care for patients with locally advanced breast cancer (BC). TIL scoring is prognostic and adds predictive value to the residual cancer burden evaluation after NAC. However, NAC induces changes in the tumor, and the reliability of TIL scoring in post-NAC samples has not yet been studied. H&E- and dual CD3/CD20 chromogenic IHC-stained tissues were scored for stromal and intra-tumoral TIL by two experienced pathologists on pre- and post-treatment BC tissues. Digital TIL scoring was performed using the HALO®image analysis software (version 2.2). In patients with residual disease, we show a good inter-pathologist correlation for stromal TIL on H&E-stained tissues (CCC value 0.73). A good correlation for scoring with both staining methods (CCC 0.81) and the digital TIL scoring (CCC 0.77) was also observed. Overall concordance for TIL scoring in patients with a complete response was however poor. This study reveals there is good reliability for TIL scoring in patients with detectable residual tumors after NAC treatment, which is comparable to the scoring of untreated breast cancer patients. Based on the good consistency observed with digital TIL scoring, the development of a validated algorithm in the future might be advantageous.
新辅助化疗(NAC)目前已成为局部晚期乳腺癌患者的标准治疗方案。肿瘤浸润淋巴细胞评分具有预后价值,并能增强新辅助化疗后残余肿瘤负荷评估的预测效能。然而,新辅助化疗会引发肿瘤微环境变化,其在治疗后样本中评分的可靠性尚未得到充分验证。本研究由两位经验丰富的病理学家分别对治疗前后的乳腺癌组织样本进行苏木精-伊红染色及CD3/CD20双染免疫组化染色,评估间质和瘤内肿瘤浸润淋巴细胞水平,并采用HALO®图像分析软件(2.2版)进行数字化评分。在存在残余病灶的患者中,苏木精-伊红染色组织的间质肿瘤浸润淋巴细胞评分显示出良好的病理学家间一致性(一致性相关系数0.73)。两种染色方法间的评分一致性(一致性相关系数0.81)及数字化评分一致性(一致性相关系数0.77)均表现良好。但在达到病理完全缓解的患者中,肿瘤浸润淋巴细胞评分总体一致性较差。本研究表明,新辅助化疗后存在可检测残余肿瘤的患者中,肿瘤浸润淋巴细胞评分具有良好可靠性,其评估效果与未经治疗的乳腺癌患者相当。基于数字化评分展现的良好一致性,未来开发经过验证的算法可能具有重要应用价值。
Tumor-Infiltrating Lymphocyte Scoring in Neoadjuvant-Treated Breast Cancer