Immune parameters associated with survival in metaplastic breast cancer

被引:28
作者
Chao, Xue [1 ,2 ]
Liu, Lili [1 ,2 ]
Sun, Peng [1 ,2 ]
Yang, Xia [1 ,2 ]
Li, Mei [1 ,2 ]
Luo, Rongzhen [1 ,2 ]
Huang, Yuhua [1 ,2 ]
He, Jiehua [1 ,2 ]
Yun, Jingping [1 ,2 ]
机构
[1] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Guangzhou, Peoples R China
[2] Sun Yat Sen Univ, Ctr Canc, Dept Pathol, 651 Dongfeng East Rd, Guangzhou 510120, Peoples R China
关键词
Metaplastic breast cancer; Immune characteristics; Prognosis; TUMOR-INFILTRATING LYMPHOCYTES; LIGAND; PD-L1; PROGNOSTIC VALUE; POOR-PROGNOSIS; EXPRESSION; CARCINOMA; CHEMOTHERAPY; TILS;
D O I
10.1186/s13058-020-01330-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background 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. Methods 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(2)) 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(2)), 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. Results 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(2), 20%), CD4+ TILs (> 250/mm(2)), and CD8+ TILs (> 70/mm(2)) 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. Conclusions 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.
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页数:11
相关论文
共 49 条
[21]   Tertiary lymphoid structures: prognostic significance and relationship with tumour-infiltrating lymphocytes in triple-negative breast cancer [J].
Lee, Hee Jin ;
Park, In Ah ;
Song, In Hye ;
Shin, Su-Jin ;
Kim, Joo Young ;
Yu, Jong Han ;
Gong, Gyungyub .
JOURNAL OF CLINICAL PATHOLOGY, 2016, 69 (05) :422-430
[22]   Presence of tertiary lymphoid structures determines the level of tumor-infiltrating lymphocytes in primary breast cancer and metastasis [J].
Lee, Miseon ;
Heo, Sun-Hee ;
Song, In Hye ;
Rajayi, Hajar ;
Park, Hye Seon ;
Park, In Ah ;
Kim, Young-Ae ;
Lee, Heejae ;
Gong, Gyungyub ;
Lee, Hee Jin .
MODERN PATHOLOGY, 2019, 32 (01) :70-80
[23]   Prognostic Significance of Programmed Death Ligand 1 Expression and Tumor-Infiltrating Lymphocytes in Axial Osteosarcoma [J].
Liu, Ping ;
Xiao, Qing ;
Zhou, Bing ;
Dai, Zhehao ;
Kang, Yijun .
WORLD NEUROSURGERY, 2019, 129 :E240-E254
[24]  
Liu YT, 2020, CLIN CANCER RES, V26, P970, DOI [10.1158/1078-0432.CCR-19-1040z, 10.1158/1078-0432.CCR-19-1040]
[25]   Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial [J].
Loi, S. ;
Michiels, S. ;
Salgado, R. ;
Sirtaine, N. ;
Jose, V. ;
Fumagalli, D. ;
Kellokumpu-Lehtinen, P-L ;
Bono, P. ;
Kataja, V. ;
Desmedt, C. ;
Piccart, M. J. ;
Loibl, S. ;
Denkert, C. ;
Smyth, M. J. ;
Joensuu, H. ;
Sotiriou, C. .
ANNALS OF ONCOLOGY, 2014, 25 (08) :1544-1550
[26]   Prognostic and Predictive Value of Tumor-Infiltrating Lymphocytes in a Phase III Randomized Adjuvant Breast Cancer Trial in Node-Positive Breast Cancer Comparing the Addition of Docetaxel to Doxorubicin With Doxorubicin-Based Chemotherapy: BIG 02-98 [J].
Loi, Sherene ;
Sirtaine, Nicolas ;
Piette, Fanny ;
Salgado, Roberto ;
Viale, Giuseppe ;
Van Eenoo, Francoise ;
Rouas, Ghizlane ;
Francis, Prudence ;
Crown, John P. A. ;
Hitre, Erika ;
de Azambuja, Evandro ;
Quinaux, Emmanuel ;
Di Leo, Angelo ;
Michiels, Stefan ;
Piccart, Martine J. ;
Sotiriou, Christos .
JOURNAL OF CLINICAL ONCOLOGY, 2013, 31 (07) :860-867
[27]   Tumor-Infiltrating CD8+ Lymphocytes Predict Clinical Outcome in Breast Cancer [J].
Mahmoud, Sahar M. A. ;
Paish, Emma Claire ;
Powe, Desmond G. ;
Macmillan, R. Douglas ;
Grainge, Matthew J. ;
Lee, Andrew H. S. ;
Ellis, Ian O. ;
Green, Andrew R. .
JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (15) :1949-1955
[28]   Prognostic Implications of PD-L1 Expression in Breast Cancer: Systematic Review and Meta-analysis of Immunohistochemistry and Pooled Analysis of Transcriptomic Data [J].
Matikas, Alexios ;
Zerdes, Ioannis ;
Lovrot, John ;
Richard, Francois ;
Sotiriou, Christos ;
Bergh, Jonas ;
Valachis, Antonios ;
Foukakis, Theodoros .
CLINICAL CANCER RESEARCH, 2019, 25 (18) :5717-5726
[29]   Increased CD4 and CD8-positive T cell infiltrate signifies good prognosis in a subset of triple-negative breast cancer [J].
Matsumoto, Hirofumi ;
Thike, Aye Aye ;
Li, Huihua ;
Yeong, Joe ;
Koo, Si-lin ;
Dent, Rebecca Alexandra ;
Tan, Puay Hoon ;
Iqbal, Jabed .
BREAST CANCER RESEARCH AND TREATMENT, 2016, 156 (02) :237-247
[30]   PD-L1 Expression in Triple-Negative Breast Cancer [J].
Mittendorf, Elizabeth A. ;
Philips, Anne V. ;
Meric-Bernstam, Funda ;
Qiao, Na ;
Wu, Yun ;
Harrington, Susan ;
Su, Xiaoping ;
Wang, Ying ;
Gonzalez-Angulo, Ana M. ;
Akcakanat, Argun ;
Chawla, Akhil ;
Curran, Michael ;
Hwu, Patrick ;
Sharma, Padmanee ;
Litton, Jennifer K. ;
Molldrem, Jeffrey J. ;
Alatrash, Gheath .
CANCER IMMUNOLOGY RESEARCH, 2014, 2 (04) :361-370