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评估肿瘤浸润淋巴细胞作为乳腺导管原位癌患者的预后生物标志物。

Evaluation of tumor infiltrating lymphocytes as a prognostic biomarker in patients with ductal carcinoma in situ of the breast.

机构信息

Setor de Mastologia da Disciplina de Ginecologia do Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, São Paulo, SP, 25101246-000, Brazil.

Setor de Patologia Mamária do Departamento de Anatomia Patológica do Instituto do Cancer de São Paulo, São Paulo, Brazil.

出版信息

Breast Cancer Res Treat. 2024 Nov;208(1):9-18. doi: 10.1007/s10549-024-07466-9. Epub 2024 Aug 24.

Abstract

PURPOSE

To assess the association between tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ (DCIS) samples and disease recurrence.

METHODS

This retrospective cohort study included women aged 18 years and older who underwent treatment between January 2007 and December 2020. Male patients, individuals diagnosed with invasive or microinvasive disease based on anatomopathological examination of surgical specimens, and those with a personal history of any other cancers were excluded. Additionally, the presence of "touching TILs" (lymphocytes in direct contact with tumor cells) and periductal desmoplasia were evaluated as complementary methods to represent the immunological microenvironment. The primary outcome was relapse-free survival based on TIL quantification adjusted for potential confounders. Pathologists assessed TILs in the sample with the highest tumor representation and quantified them as a percentage. Survival was evaluated using Kaplan‒Meier curves, log-rank tests, and Cox regression models.

RESULTS

A total of 191 patients met the eligibility criteria. The mean follow-up duration was 77.2 months, with a recurrence rate of 9.2%. Patients with TILs ≥ 17% had a greater risk of recurrence (HR 2.97, 95% CI 1.17-7.51; p = 0.02). Additionally, focal necrosis (HR 6.4, 95% CI 1.39-34.71; p = 0.018) or comedonecrosis (HR 4.53, 95% CI 1.34-15.28; p = 0.015) were associated with increased recurrence risk. According to the multivariate model, comedonecrosis and TILs ≥ 17% were significantly associated with recurrence (p = 0.034 and p = 0.035, respectively). Regarding the evaluations of "touching TILs" and periductal desmoplasia, no statistical significance was found when assessing their association with disease recurrence.

CONCLUSION

In our cohort, a high percentage of TILs (≥ 17%) and the presence of comedonecrosis were independently associated with DCIS recurrence.

摘要

目的

评估导管原位癌(DCIS)样本中肿瘤浸润淋巴细胞(TILs)与疾病复发之间的关联。

方法

本回顾性队列研究纳入了 2007 年 1 月至 2020 年 12 月期间接受治疗的年龄在 18 岁及以上的女性患者。排除男性患者、基于手术标本解剖病理学检查诊断为浸润性或微浸润性疾病的患者以及有其他任何癌症病史的患者。此外,还评估了“触诊 TILs”(与肿瘤细胞直接接触的淋巴细胞)和导管周围纤维组织增生作为代表免疫微环境的补充方法。主要结局是根据潜在混杂因素调整 TIL 定量的无复发生存率。病理学家评估了具有最高肿瘤代表性的样本中的 TILs,并将其量化为百分比。使用 Kaplan-Meier 曲线、对数秩检验和 Cox 回归模型评估生存情况。

结果

共有 191 名患者符合入选标准。平均随访时间为 77.2 个月,复发率为 9.2%。TILs≥17%的患者复发风险更高(HR 2.97,95%CI 1.17-7.51;p=0.02)。此外,局灶性坏死(HR 6.4,95%CI 1.39-34.71;p=0.018)或粉刺样坏死(HR 4.53,95%CI 1.34-15.28;p=0.015)与复发风险增加相关。根据多变量模型,粉刺样坏死和 TILs≥17%与复发显著相关(p=0.034 和 p=0.035)。关于“触诊 TILs”和导管周围纤维组织增生的评估,未发现其与疾病复发相关的统计学意义。

结论

在本队列中,高百分比的 TILs(≥17%)和粉刺样坏死的存在与 DCIS 复发独立相关。

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