Badve Sunil S, Cho Sanghee, Lu Xiaoyu, Cao Sha, Ghose Soumya, Thike Aye Aye, Tan Puay Hoon, Ocal Idris Tolgay, Generali Daniele, Zanconati Fabrizio, Harris Adrian L, Ginty Fiona, Gökmen-Polar Yesim
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Winship Cancer Institute, Atlanta, GA 30322, USA.
Cancers (Basel). 2022 Aug 13;14(16):3916. doi: 10.3390/cancers14163916.
Tumor-infiltrating lymphocytes (TILs) are prognostic in invasive breast cancer. However, their prognostic significance in ductal carcinoma in situ (DCIS) has been controversial. To investigate the prognostic role of TILs in DCIS outcome, we used different scoring methods for TILs in multi-national cohorts from Asian and European women. Self-described race was genetically confirmed using QC Infinium array combined with radmixture software. Stromal TILs, touching TILs, circumferential TILs, and hotspots were quantified on H&E-stained slides and correlated with the development of second breast cancer events (BCE) and other clinico-pathological variables. In univariate survival analysis, age older than 50 years, hormone receptor positivity and the presence of circumferential TILs were weakly associated with the absence of BCE at the 5-year follow-up in all cohorts (p < 0.03; p < 0.02; and p < 0.02, respectively, adjusted p = 0.11). In the multivariable analysis, circumferential TILs were an independent predictor of a better outcome (Wald test p = 0.01), whereas younger age was associated with BCE. Asian patients were younger with larger, higher grade, HR negative DCIS lesions, and higher TIL variables. The spatial arrangement of TILs may serve as a better prognostic indicator in DCIS cases than stromal TILs alone and may be added in guidelines for TILs evaluation in DCIS.
肿瘤浸润淋巴细胞（TILs）对浸润性乳腺癌具有预后价值。然而，它们在导管原位癌（DCIS）中的预后意义一直存在争议。为了研究TILs在DCIS预后中的作用，我们对来自亚洲和欧洲女性的多国队列中的TILs使用了不同的评分方法。使用QC Infinium阵列结合radmixture软件对自我描述的种族进行基因确认。在苏木精和伊红（H&E）染色的切片上对基质TILs、接触性TILs、周边TILs和热点进行定量，并与第二原发性乳腺癌事件（BCE）的发生以及其他临床病理变量相关联。在单变量生存分析中，所有队列中年龄大于50岁、激素受体阳性以及存在周边TILs与5年随访时无BCE的情况呈弱相关（p < 0.03；p < 0.02；以及p < 0.02，调整后p = 0.11）。在多变量分析中，周边TILs是预后较好的独立预测因素（Wald检验p = 0.01），而年龄较小与BCE相关。亚洲患者年龄较小，DCIS病变更大、分级更高、激素受体阴性，且TIL变量更高。与单独的基质TILs相比，TILs的空间排列可能是DCIS病例中更好的预后指标，并且可能会被纳入DCIS中TILs评估的指南。
