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Original Article
Loss of Human Leukocyte Antigen Class I Expression Is Associated with Poor Prognosis in Patients with Advanced Breast Cancer
Hong Sik Park, Uiju Cho, So Young Im, Chang Young Yoo, Ji Han Jung, Young Jin Suh, Hyun Joo Choi
J Pathol Transl Med. 2019;53(2):75-85.   Published online November 14, 2018
DOI: https://doi.org/10.4132/jptm.2018.10.11
  • 6,424 View
  • 178 Download
  • 24 Web of Science
  • 27 Crossref
AbstractAbstract PDF
Background
Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear.
Methods
We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed.
Results
Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II–IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I–positive tumors than in HLA-I–negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort.
Conclusions
Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.

Citations

Citations to this article as recorded by  
  • Comment on “Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta‑Analysis”
    Wei Han, Li-zhou Shi, Yu-wei Zhang, Hao-nan Wang
    Molecular Diagnosis & Therapy.2024; 28(2): 237.     CrossRef
  • Immunotherapy resistance in solid tumors: mechanisms and potential solutions
    Daniel S. Lefler, Steven A. Manobianco, Babar Bashir
    Cancer Biology & Therapy.2024;[Epub]     CrossRef
  • Cancer Immunology: Immune Escape of Tumors—Expression and Regulation of HLA Class I Molecules and Its Role in Immunotherapies
    Yuan Wang, Simon Jasinski-Bergner, Claudia Wickenhauser, Barbara Seliger
    Advances in Anatomic Pathology.2023; 30(3): 148.     CrossRef
  • In Silico Pipeline to Identify Tumor-Specific Antigens for Cancer Immunotherapy Using Exome Sequencing Data
    Diego Morazán-Fernández, Javier Mora, Jose Arturo Molina-Mora
    Phenomics.2023; 3(2): 130.     CrossRef
  • HLA and tumour immunology: immune escape, immunotherapy and immune-related adverse events
    Ning Jiang, Yue Yu, Dawei Wu, Shuhang Wang, Yuan Fang, Huilei Miao, Peiwen Ma, Huiyao Huang, Min Zhang, Yu Zhang, Yu Tang, Ning Li
    Journal of Cancer Research and Clinical Oncology.2023; 149(2): 737.     CrossRef
  • Relationship between Systemic Inflammatory Markers, GLUT1 Expression, and Maximum 18F-Fluorodeoxyglucose Uptake in Non-Small Cell Lung Carcinoma and Their Prognostic Significance
    Sonya Youngju Park, Deog-Gon Cho, Byoung-Yong Shim, Uiju Cho
    Diagnostics.2023; 13(6): 1013.     CrossRef
  • Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta-Analysis
    Weiqiang Qiao, Zhiqiang Jia, Wanying Guo, Qipeng Liu, Xiao Guo, Miao Deng
    Molecular Diagnosis & Therapy.2023; 27(5): 573.     CrossRef
  • Challenges and solutions for therapeuticTCR‐based agents
    Manish Malviya, Zita E. H. Aretz, Zaki Molvi, Jayop Lee, Stephanie Pierre, Patrick Wallisch, Tao Dao, David A. Scheinberg
    Immunological Reviews.2023; 320(1): 58.     CrossRef
  • Molecular mechanisms of impaired antigenic presentation as a cause of tumor escape from immune surveillance
    A.A. Korotaeva, A.A. Borunova, A.Yu. Kuzevanova, T.N. Zabotina, A.A. Alimov
    Arkhiv patologii.2023; 85(6): 76.     CrossRef
  • Immune Escape Mechanism of Cancer
    Ayse Caner
    Current Molecular Biology Reports.2023; 10(1): 9.     CrossRef
  • Upregulation of MHC I Antigen Processing Machinery Gene Expression in Breast Cancer Cells by Trichostatin A
    A. H. Murtadha, N. A. Sharudin, I. I. M. Azahar, A. T. Che Has, N. F. Mokhtar
    Molecular Biology.2023; 57(6): 1212.     CrossRef
  • Human Leukocyte Antigen Class I Antigen-Processing Machinery Upregulation by Anticancer Therapies in the Era of Checkpoint Inhibitors
    Ananthan Sadagopan, Theodoros Michelakos, Gabriella Boyiadzis, Cristina Ferrone, Soldano Ferrone
    JAMA Oncology.2022; 8(3): 462.     CrossRef
  • Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response
    Brandie C. Taylor, Justin M. Balko
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • Immune Checkpoint Blockade in Hormone Receptor-Positive Breast Cancer: Resistance Mechanisms and Future Perspectives
    Ioannis A. Vathiotis, Ioannis Trontzas, Niki Gavrielatou, Georgia Gomatou, Nikolaos K. Syrigos, Elias A. Kotteas
    Clinical Breast Cancer.2022; 22(7): 642.     CrossRef
  • Aberrant synaptophysin expression in classic Hodgkin lymphoma
    Soyoung Im, Jeong-A. Kim, Gyeongsin Park, Uiju Cho
    Diagnostic Pathology.2022;[Epub]     CrossRef
  • Expression of HLA class I is associated with immune cell infiltration and patient outcome in breast cancer
    Song-Hee Han, Milim Kim, Yul Ri Chung, Ji Won Woo, Hye Yeon Choi, So Yeon Park
    Scientific Reports.2022;[Epub]     CrossRef
  • Immune landscape and therapeutic strategies: new insights into PD-L1 in tumors
    Yuan Wei, Xiao Xiao, Xiang-Ming Lao, Limin Zheng, Dong-Ming Kuang
    Cellular and Molecular Life Sciences.2021; 78(3): 867.     CrossRef
  • Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of breast cancer
    Leisha A Emens, Sylvia Adams, Ashley Cimino-Mathews, Mary L Disis, Margaret E Gatti-Mays, Alice Y Ho, Kevin Kalinsky, Heather L McArthur, Elizabeth A Mittendorf, Rita Nanda, David B Page, Hope S Rugo, Krista M Rubin, Hatem Soliman, Patricia A Spears, Sara
    Journal for ImmunoTherapy of Cancer.2021; 9(8): e002597.     CrossRef
  • Resistance mechanisms to checkpoint inhibitors
    Sarah A Weiss, Mario Sznol
    Current Opinion in Immunology.2021; 69: 47.     CrossRef
  • The Immunology of Hormone Receptor Positive Breast Cancer
    Jonathan Goldberg, Ricardo G. Pastorello, Tuulia Vallius, Janae Davis, Yvonne Xiaoyong Cui, Judith Agudo, Adrienne G. Waks, Tanya Keenan, Sandra S. McAllister, Sara M. Tolaney, Elizabeth A. Mittendorf, Jennifer L. Guerriero
    Frontiers in Immunology.2021;[Epub]     CrossRef
  • B4GALNT2 Gene Promotes Proliferation, and Invasiveness and Migration Abilities of Model Triple Negative Breast Cancer (TNBC) Cells by Interacting With HLA-B Protein
    Pu Yu, Lili Zhu, Kang Cui, Yabing Du, Chaojie Zhang, Wang Ma, Jia Guo
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Recurrence biomarkers of triple negative breast cancer treated with neoadjuvant chemotherapy and anti-EGFR antibodies
    Nina Radosevic-Robin, Pier Selenica, Yingjie Zhu, Helen H. Won, Michael F. Berger, Lorenzo Ferrando, Emiliano Cocco, Maud Privat, Flora Ponelle-Chachuat, Catherine Abrial, Jean-Marc Nabholtz, Frederique Penault-Llorca, Jorge S. Reis-Filho, Maurizio Scaltr
    npj Breast Cancer.2021;[Epub]     CrossRef
  • Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?
    Liam Masterson, James Howard, Jazmina Gonzalez‐Cruz, Christopher Jackson, Catherine Barnett, Lewis Overton, Howard Liu, Rahul Ladwa, Fiona Simpson, Margie McGrath, Ben Wallwork, Terry Jones, Christian Ottensmeier, Melvin L.K. Chua, Chris Perry, Rajiv Khan
    International Journal of Cancer.2020; 146(8): 2305.     CrossRef
  • Co-expression of HLA-I loci improved prognostication in HER2+ breast cancers
    Julia Y. Tsang, Chun-Sing Ho, Yun-Bi Ni, Yan Shao, Ivan K. Poon, Siu-Ki Chan, Sai-Yin Cheung, Ka-Ho Shea, Monalyn Marabi, Gary M. Tse
    Cancer Immunology, Immunotherapy.2020; 69(5): 799.     CrossRef
  • Breast cancer patients overall survival depends on a combination of the polymorphisms of tumor necrosis factor gene and HLA-haplotypes
    T.F. Malivanova, E.V. Alferova, A.S. Ostashkin, T.A. Astrelina, N.N. Mazurenko
    Molecular Genetics Microbiology and Virology (Russian version).2020; 38(1): 40.     CrossRef
  • The Overall Survival of Breast Cancer Patients Depends on a Combination of Polymorphisms of Tumor Necrosis Factor Gene and HLA Haplotypes
    T. F. Malivanova, E. V. Alferova, A. S. Ostashkin, T. A. Astrelina, N. N. Mazurenko
    Molecular Genetics, Microbiology and Virology.2020; 35(1): 38.     CrossRef
  • The Emergence of Natural Killer Cells as a Major Target in Cancer Immunotherapy
    Fernando Souza-Fonseca-Guimaraes, Joseph Cursons, Nicholas D. Huntington
    Trends in Immunology.2019; 40(2): 142.     CrossRef
Case Report
Systemic Plasmacytosis: A Case Report with a Review of the Literature.
Sung Hak Lee, Chang Young Yoo, Ji Han Jung, Jin Young Yoo, Suk Jin Kang, Chang Suk Kang
Korean J Pathol. 2011;45(6):632-638.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.632
  • 3,444 View
  • 30 Download
  • 3 Crossref
AbstractAbstract PDF
Systemic plasmacytosis is an uncommon disorder characterized by widely disseminated macular skin eruptions composed of polyclonal lymphoplasmacytic infiltrates associated with variable extracutaneous involvement. An aggressive clinical course has been observed in a small number of patients, but most cases have followed chronic and benign clinical course without spontaneous remission. Previously reported cases of this entity have been described almost exclusively in Japanese patients. We recently experienced a case of systemic plasmacytosis in a 48-year-old Korean female patient. Initial skin biopsy specimen revealed patchy perivascular and periadnexal infiltrates of mature plasma cells. Serum immunoelectrophoresis revealed polyclonal hypergammaglobulinemia, and polyclonal plasmacytosis was noted on the subsequent biopsy specimens of left supraclavicular and axillary lymph nodes. Multiple tiny pulmonary nodules appeared six years after the initial cutaneous presentation and were found to be of the same histologic appearance. We herein report a rare case of systemic plasmacytosis with a review of the literature.

Citations

Citations to this article as recorded by  
  • Cutaneous plasmacytosis with mast cell infiltration
    Sarina Jain, RohitV Hede, UdayS Khopkar
    Indian Journal of Dermatology, Venereology and Leprology.2020; 86(1): 91.     CrossRef
  • Plasmocitosis cutánea en un varón de raza blanca
    A. López-Gómez, T. Salas-García, A. Ramírez-Andreo, E. Poblet-Martínez
    Actas Dermo-Sifiliográficas.2015; 106(6): 520.     CrossRef
  • Cutaneous Plasmacytosis in a White Man
    A. López-Gómez, T. Salas-García, A. Ramírez-Andreo, E. Poblet-Martínez
    Actas Dermo-Sifiliográficas (English Edition).2015; 106(6): 520.     CrossRef
Original Article
Predictive Significance of KRAS and Tau for Chemoresponse in Advanced Non-Small-Cell Lung Cancer.
Jinyoung Yoo, Byoung Yong Shim, Chang Young Yoo, Seok Jin Kang, Kyo Young Lee
Korean J Pathol. 2009;43(5):435-440.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.435
  • 3,203 View
  • 26 Download
  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
Taxane-platinum combinations are often used as first-line treatments for patients with advanced non-small cell lung cancer (NSCLC). Response to chemotherapy for these patients is still poor. The aim of our study was to investigate, for this disease, whether KRAS and Tau proteins affect responses to taxane-platinum combinations.
METHODS
Expression of KRAS and Tau was examined immunohistochemically in 71 tumor samples obtained from patients with stage IIIB or IV NSCLC prior to combination therapy. Expression was correlated with tumor responses.
RESULTS
The response rate was 55% (39 of 71). KRAS and Tau were expressed in seven (10%) and 31 (44%) patients, respectively. All seven KRAS-positive patients were non-responders (p=0.014). Among Tau-positive patients, 35% (11 of 31) responded to therapy, whereas a partial response was observed in 70% (28 of 40) of Tau-negatives (p=0.045). Two were positive for both, and they were non-responders. In patients negative for both, the response rate was 71% (25 of 35) (p=0.012).
CONCLUSIONS
Expression of KRAS and Tau are significantly correlated with poor responses to this combination therapy in advanced NSCLC patients, and may be a useful marker for chemoresistance.

Citations

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  • Emerging Evidences for an Implication of the Neurodegeneration-Associated Protein TAU in Cancer
    Stéphanie Papin, Paolo Paganetti
    Brain Sciences.2020; 10(11): 862.     CrossRef

J Pathol Transl Med : Journal of Pathology and Translational Medicine