Swisher Shannon K, Wu Yun, Castaneda Carlos A, Lyons Genvieve R, Yang Fei, Tapia Coya, Wang Xiuhong, Casavilca Sandro A A, Bassett Roland, Castillo Miluska, Sahin Aysegul, Mittendorf Elizabeth A
Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ann Surg Oncol. 2016 Jul;23(7):2242-8. doi: 10.1245/s10434-016-5173-8. Epub 2016 Mar 10.
The presence of tumor-infiltrating lymphocytes (TILs) in breast tumors is prognostic and predictive, suggesting that TILs may be an important biomarker. Recently, an international TILs working group formulated consensus recommendations for TIL evaluation. The current study was performed to determine interobserver agreement using that methodology.
Tumor-infiltrating lymphocytes were assessed on a single hematoxylin and eosin (H&E)-stained slide obtained from the core biopsy of 75 triple-negative breast cancers. Four pathologists independently reviewed each slide and evaluated stromal TILs (sTILs) and intratumoral TIL (iTILs). The kappa statistic was used to estimate interobserver agreement for identification of sTILs, and the intraclass correlation coefficient (ICC) was used to estimate the agreement among observers for iTILs. Cases with poor agreement were reviewed to identify pathologic factors that may contribute to the lack of agreement.
The kappa statistic for sTIL evaluation was 0.57 (standard error, 0.04). For iTILs, the ICC calculated to determine internal consistency within raters was 0.65 (95 % confidence interval [CI] 0.56-0.74; p < 0.0001), and the ICC calculated to determine agreement among raters was 0.62 (95 % CI 0.50-0.72; p < 0.0001). In 10 cases (13 %), there was not agreement between three of four pathologists. The pathologic features contributing to difficulty in TIL enumeration included marked individual tumor cell necrosis or apoptosis, the presence of reactive plasma cells mimicking tumor cells, plasmatoid tumor cells, and accurate quantification of TILs in specimens with focal areas of heavy immune infiltrate.
Acceptable agreement in TIL enumeration was observed, suggesting that the proposed methodology can be used to facilitate the use of TILs as a biomarker in research and clinical trial settings.
乳腺肿瘤中肿瘤浸润淋巴细胞（TILs）的存在具有预后和预测价值，提示TILs可能是一种重要的生物标志物。最近，一个国际TILs工作组制定了TIL评估的共识建议。本研究旨在使用该方法确定观察者间的一致性。
对从75例三阴性乳腺癌的粗针活检获取的一张苏木精-伊红（H&E）染色切片上的肿瘤浸润淋巴细胞进行评估。四位病理学家独立审查每张切片，并评估基质TILs（sTILs）和瘤内TILs（iTILs）。kappa统计量用于估计识别sTILs的观察者间一致性，组内相关系数（ICC）用于估计观察者间对iTILs的一致性。对一致性差的病例进行审查，以确定可能导致一致性缺乏的病理因素。
sTIL评估的kappa统计量为0.57（标准误，0.04）。对于iTILs，计算得出的用于确定评分者内部一致性的ICC为0.65（95%置信区间[CI]0.56 - 0.74；p < 0.0001），计算得出的用于确定评分者间一致性的ICC为0.62（95% CI 0.50 - 0.72；p < 0.0001）。在10例（13%）病例中，四位病理学家中有三位之间存在不一致。导致TIL计数困难的病理特征包括明显的单个肿瘤细胞坏死或凋亡、存在模仿肿瘤细胞的反应性浆细胞、浆细胞样肿瘤细胞以及在免疫浸润严重的局部区域标本中TIL的准确量化。
观察到TIL计数具有可接受的一致性，表明所提出的方法可用于促进TILs在研究和临床试验环境中作为生物标志物的应用。
