Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
Department of Pathology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510120, People's Republic of China.
Breast Cancer Res. 2020 Aug 18;22(1):92. doi: 10.1186/s13058-020-01330-6.
Metaplastic breast carcinoma (MBC) is a rare histological type of breast cancer, which commonly shows resistance to standard therapies and is associated with poor prognosis. The immune microenvironment in MBC and its significance has not been well established due to its low incurrence rate and complex components. We aimed to investigate the diversity of immune parameters including subsets of TILs and PDL1/PD1 expression in MBC, as well as its correlation with prognosis.
A total of 60 patients diagnosed with MBC from January 2006 to December 2017 were included in our study. The percentage (%) and quantification (per mm) of TILs and presence of tertiary lymphoid structures (TLS) were evaluated by hematoxylin and eosin staining (HE). The quantification of CD4+, CD8+ TILs (per mm), and PD-1/PDL1 expression were evaluated through immunohistochemistry and analyzed in relation to clinicopathological characteristics. A ≥ 1% membranous or cytoplasmatic expression of PD1 and PDL1 was considered a positive expression.
We found squamous cell carcinoma MBC (33/60, 55%) exhibiting most TILs of all the MBC subtypes (p = 0.043). Thirty-three of 60 (50%) of the patients had coexisting invasive ductal carcinoma of no special type (IDC-NST), and the average percentage of TILs in MBC components was lower compared with NST components (p < 0.001). Thirty (50%) patients exhibited positive (≥ 1%) PDL1 expression in their tumor cells, while 36 (60%) had positive (≥ 1%) PDL1 expression in their TILs. Twenty-seven (45%) of all the patients had positive (≥ 1%) PD1 expression in their tumor cells and 33 (55%) had PD1-positive (≥ 1%) stromal TILs. More CD8+ TILs were associated with positive PDL1 expression of tumor cells as well as positive PD1 expression in stromal cells. Greater number of stromal TILS (> 300/mm, 20%), CD4+ TILs (> 250/mm), and CD8+ TILs (> 70/mm) in MBC were found associated with longer disease-free survival. Positive expression of PDL1 in tumor cells (≥ 1%) and PD1 in stromal cells (≥ 1%) were also associated with longer survival.
The immune characteristics differ in various subtypes as well as components of MBC. Immune parameters are key predictive factors of MBC and provide the clinical significance of applying immune checkpoint therapies in patients with MBC.
化生性乳腺癌（MBC）是一种罕见的乳腺癌组织学类型，通常对标准治疗具有抗药性，且预后较差。由于其发病率低且成分复杂，MBC 中的免疫微环境及其意义尚未得到充分确立。我们旨在研究包括 TIL 亚群和 PDL1/PD1 表达在内的免疫参数在 MBC 中的多样性，并探讨其与预后的相关性。
本研究共纳入 2006 年 1 月至 2017 年 12 月期间诊断为 MBC 的 60 例患者。通过苏木精和伊红染色（HE）评估 TIL 的百分比（%）和定量（每平方毫米）以及三级淋巴结构（TLS）的存在。通过免疫组织化学评估 CD4+、CD8+TIL（每平方毫米）和 PD-1/PDL1 表达，并分析与临床病理特征的关系。膜或细胞质中 PD1 和 PDL1 表达≥1%被认为是阳性表达。
我们发现，鳞状细胞癌 MBC（33/60，55%）的所有 MBC 亚型中 TIL 比例最高（p=0.043）。60 例患者中有 33 例（50%）同时存在非特殊型浸润性导管癌（IDC-NST），且 MBC 成分中的 TIL 百分比低于 NST 成分（p<0.001）。30 例（50%）患者的肿瘤细胞中存在阳性（≥1%）PDL1 表达，而 36 例（60%）患者的肿瘤浸润淋巴细胞中存在阳性（≥1%）PDL1 表达。所有患者中有 27 例（45%）的肿瘤细胞中存在阳性（≥1%）PD1 表达，33 例（55%）的肿瘤间质中存在 PD1 阳性（≥1%）TIL。更多的 CD8+TIL 与肿瘤细胞的 PDL1 阳性表达以及间质细胞的 PD1 阳性表达有关。MBC 中更多的基质 TILS（>300/mm，20%）、CD4+TILs（>250/mm）和 CD8+TILs（>70/mm）与无病生存期延长有关。肿瘤细胞中 PDL1 阳性（≥1%）和基质细胞中 PD1 阳性（≥1%）的表达也与生存时间延长有关。
MBC 的不同亚型和成分存在免疫特征差异。免疫参数是 MBC 的关键预测因素，为在 MBC 患者中应用免疫检查点治疗提供了临床意义。
