Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Asan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Mod Pathol. 2019 Jan;32(1):70-80. doi: 10.1038/s41379-018-0113-8. Epub 2018 Aug 28.
The level of tumor-infiltrating lymphocytes and presence of tertiary lymphoid structures are significant prognostic and predictive factors in primary breast cancer. However, the understanding about differences in tumor-infiltrating lymphocytes and tertiary lymphoid structures at various metastatic sites or between primary breast tumors and metastatic sites is limited. A total of 335 cases of metastatic breast cancer from four metastatic sites (lung, liver, brain, and ovary) were included. We analyzed the percentages of tumor-infiltrating lymphocytes and presence of tertiary lymphoid structures in the primary and metastatic sites. The mean level of tumor-infiltrating lymphocytes in the lung metastases was higher than in the liver, brain, ovary, and matched primary tumors, while metastatic tumors of the liver and brain showed lower levels of tumor-infiltrating lymphocytes than primary tumors. Tertiary lymphoid structures were only found in the lung and liver, and in cases of brain metastases the change of tertiary lymphoid structures from present to absent significantly affected the level of tumor-infiltrating lymphocytes in metastases compared with that in matched primary tumors. Patients with a lower histological grade, hormone receptor positivity in primary tumors and metastases, a lower level of tumor-infiltrating lymphocytes and absence of tertiary lymphoid structures in primary tumors, a higher level of tumor-infiltrating lymphocytes and presence of tertiary lymphoid structures in metastases, and lung metastases showed significantly better overall survival. Our results showed that metastatic breast tumors in the lung had more tumor-infiltrating lymphocytes than did tumors at other sites and matched primary tumors. In addition, the presence of tertiary lymphoid structures in metastatic sites is a critical factor for the level of tumor-infiltrating lymphocytes.
肿瘤浸润淋巴细胞水平和三级淋巴结构的存在是原发性乳腺癌重要的预后和预测因素。然而，对于不同转移部位或原发性乳腺癌与转移部位之间的肿瘤浸润淋巴细胞和三级淋巴结构的差异，人们的了解是有限的。本研究共纳入了来自四个转移部位（肺、肝、脑和卵巢）的 335 例转移性乳腺癌病例。我们分析了原发性和转移性部位的肿瘤浸润淋巴细胞百分比和三级淋巴结构的存在情况。肺转移灶中的肿瘤浸润淋巴细胞水平高于肝、脑、卵巢和匹配的原发性肿瘤，而肝和脑转移瘤中的肿瘤浸润淋巴细胞水平低于原发性肿瘤。三级淋巴结构仅在肺和肝中发现，脑转移病例中三级淋巴结构从存在变为不存在，与匹配的原发性肿瘤相比，转移灶中的肿瘤浸润淋巴细胞水平显著降低。与其他部位和匹配的原发性肿瘤相比，肺转移的乳腺癌肿瘤中具有更低的组织学分级、原发性和转移性肿瘤中激素受体阳性、原发性肿瘤中肿瘤浸润淋巴细胞水平较低且无三级淋巴结构、转移性肿瘤中肿瘤浸润淋巴细胞水平较高且有三级淋巴结构的患者，总体生存情况显著更好。我们的结果表明，与其他部位和匹配的原发性肿瘤相比，肺转移的乳腺癌肿瘤中具有更多的肿瘤浸润淋巴细胞。此外，转移部位存在三级淋巴结构是肿瘤浸润淋巴细胞水平的关键因素。
