Tumor Infiltrating Lymphocytes in Multi-National Cohorts of Ductal Carcinoma In Situ (DCIS) of Breast.
Tumor Infiltrating Lymphocytes in Multi-National Cohorts of Ductal Carcinoma In Situ (DCIS) of Breast.
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DOI：
10.3390/cancers14163916
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发表时间：
2022-08-13
期刊：
影响因子：
5.2
通讯作者：
Gokmen-Polar, Yesim
中科院分区：
文献类型：
--
作者：
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;Gokmen-Polar, Yesim
肿瘤浸润淋巴细胞（TIL）对浸润性乳腺癌具有预后意义。然而，它们在导管原位癌（DCIS）中的预后意义一直存在争议。我们在亚洲和欧洲女性的跨国队列中使用了不同的 TIL 评分方法。在 H&E 染色的载玻片上对基质 TIL、接触 TIL、圆周 TIL 和热点进行量化，并与第二次乳腺癌事件 (BCE) 和其他临床病理变量的发展相关。在所有队列中，老年女性、激素受体阳性和周围 TIL 的存在与 5 年随访时不存在 BCE 存在微弱相关。在多变量分析中，具有圆周 TIL 的老年女性发生 BCE 的可能性较小（Wald 检验 p = 0.01）。亚洲患者更年轻，具有更大、更高级别、HR 阴性的 DCIS 病变和更高的 TIL 变量。 TIL 的空间排列可能是 DCIS 病例中比单独基质 TIL 更好的预后指标。肿瘤浸润淋巴细胞（TIL）对浸润性乳腺癌具有预后意义。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 TIL 在 DCIS 结果中的预后作用，我们在亚洲和欧洲女性的跨国队列中使用了不同的 TIL 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 H&E 染色的载玻片上对基质 TIL、接触 TIL、圆周 TIL 和热点进行量化，并与第二次乳腺癌事件 (BCE) 和其他临床病理变量的发展相关。在单变量生存分析中，所有队列中年龄超过 50 岁、激素受体阳性和周围 TIL 的存在与 5 年随访时 BCE 的缺失呈弱相关（分别为 p < 0.03、p < 0.02 和 p < 0.02，调整 p = 0.11）。在多变量分析中，圆周 TIL 是更好结果的独立预测因子（Wald 检验 p = 0.01），而较年轻的年龄与 BCE 相关。亚洲患者更年轻，具有更大、更高级别、HR 阴性的 DCIS 病变和更高的 TIL 变量。 TIL 的空间排列可能是 DCIS 病例中比单独基质 TIL 更好的预后指标，并且可以添加到 DCIS 的 TIL 评估指南中。
Tumor-infiltrating lymphocytes (TILs) are prognostic in invasive breast cancer. However, their prognostic significance in ductal carcinoma in situ (DCIS) has been controversial. We used different scoring methods for TILs in multi-national cohorts from Asian and European women. 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. Older women, hormone receptor positivity, and the presence of circumferential TILs were weakly associated with the absence of BCE at 5-year follow-up in all cohorts. In multivariable analysis, older women with circumferential TILs were less likely to develop BCEs (Wald test p = 0.01). 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. 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.
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