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- Unusual biclonal IgA plasma cell myeloma with aberrant expression of high-risk immunophenotypes: first report of a new diagnostic and clinical challenge
- Carlos A. Monroig-Rivera, Clara N. Finch Cruz
- J Pathol Transl Med. 2023;57(2):132-137. Published online March 14, 2023
- DOI: https://doi.org/10.4132/jptm.2023.02.07
- 1,929 View
- 123 Download
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Abstract
PDF - IgA plasma cell myeloma (PCM) has been linked to molecular abnormalities that confer a higher risk for adverse patient outcomes. However, since IgA PCM only accounts for approximately 20% of all PCM, there are very few reports on high-risk IgA PCM. Moreover, no such reports are found on the more infrequent biclonal IgA PCM. Hence, we present a 65-year-old Puerto Rican female with acute abdominal pain, concomitant hypercalcemia, and acute renal failure. Protein electrophoresis with immunofixation found high IgA levels and detected a biclonal IgA gammopathy with kappa specificity. Histomorphologically, bone marrow showed numerous abnormal plasma cells (32%) replacing over 50% of the marrow stroma. Immunophenotyping analysis detected CD45-negative plasma cells aberrantly expressing CD33, CD43, OCT-2, and c-MYC. Chromosomal analysis revealed multiple abnormalities including the gain of chromosome 1q. Thus, we report on an unusual biclonal IgA PCM and the importance of timely diagnosing aggressive plasma cell neoplasms.
Original Article
- Immunohistochemical expression of programmed death-ligand 1 and CD8 in glioblastomas
- Dina Mohamed El Samman, Manal Mohamed El Mahdy, Hala Sobhy Cousha, Zeinab Abd El Rahman Kamar, Khaled Abdel Karim Mohamed, Hoda Hassan Abou Gabal
- J Pathol Transl Med. 2021;55(6):388-397. Published online October 14, 2021
- DOI: https://doi.org/10.4132/jptm.2021.08.04
- 3,580 View
- 174 Download
- 3 Web of Science
- 3 Crossref
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Abstract
PDF
- Background
Glioblastoma is the most aggressive primary malignant brain tumor in adults and is characterized by poor prognosis. Immune evasion occurs via programmed death-ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) interaction. Some malignant tumors have responded to PD-L1/PD-1 blockade treatment strategies, and PD-L1 has been described as a potential predictive biomarker. This study discussed the expression of PD-L1 and CD8 in glioblastomas.
Methods
Thirty cases of glioblastoma were stained immunohistochemically for PD-L1 and CD8, where PD-L1 expression in glioblastoma tumor tissue above 1% is considered positive and CD-8 is expressed in tumor infiltrating lymphocytes. The expression of each marker was correlated with clinicopathologic parameters. Survival analysis was conducted to correlate progression-free survival (PFS) and overall survival (OS) with PD-L1 and CD8 expression.
Results
Diffuse/fibrillary PD-L1 was expressed in all cases (mean expression, 57.6%), whereas membranous PD-L1 was expressed in six of 30 cases. CD8-positive tumor-infiltrating lymphocytes (CD8+ TILs) had a median expression of 10%. PD-L1 and CD8 were positively correlated (p = .001). High PD-L1 expression was associated with worse PFS and OS (p = .026 and p = .001, respectively). Correlation of CD8+ TILs percentage with age, sex, tumor site, laterality, and outcomes were statistically insignificant. Multivariate analysis revealed that PD-L1 was the only independent factor that affected prognosis.
Conclusions
PD-L1 expression in patients with glioblastoma is robust; higher PD-L1 expression is associated with lower CD8+ TIL expression and worse prognosis. -
Citations
Citations to this article as recorded by
- Tumor-associated microenvironment, PD-L1 expression and their relationship with immunotherapy in glioblastoma, IDH-wild type: A comprehensive review with emphasis on the implications for neuropathologists
Giuseppe Broggi, Giuseppe Angelico, Jessica Farina, Giordana Tinnirello, Valeria Barresi, Magda Zanelli, Andrea Palicelli, Francesco Certo, Giuseppe Barbagallo, Gaetano Magro, Rosario Caltabiano
Pathology - Research and Practice.2024; 254: 155144. CrossRef - Analysis of PD-L1 and CD3 Expression in Glioblastoma Patients and Correlation with Outcome: A Single Center Report
Navid Sobhani, Victoria Bouchè, Giovanni Aldegheri, Andrea Rocca, Alberto D’Angelo, Fabiola Giudici, Cristina Bottin, Carmine Antonio Donofrio, Maurizio Pinamonti, Benvenuto Ferrari, Stefano Panni, Marika Cominetti, Jahard Aliaga, Marco Ungari, Antonio Fi
Biomedicines.2023; 11(2): 311. CrossRef - Immuno-PET Imaging of Tumour PD-L1 Expression in Glioblastoma
Gitanjali Sharma, Marta C. Braga, Chiara Da Pieve, Wojciech Szopa, Tatjana Starzetz, Karl H. Plate, Wojciech Kaspera, Gabriela Kramer-Marek
Cancers.2023; 15(12): 3131. CrossRef
- Tumor-associated microenvironment, PD-L1 expression and their relationship with immunotherapy in glioblastoma, IDH-wild type: A comprehensive review with emphasis on the implications for neuropathologists
Review
- Programmed cell death-ligand 1 assessment in urothelial carcinoma: prospect and limitation
- Kyu Sang Lee, Gheeyoung Choe
- J Pathol Transl Med. 2021;55(3):163-170. Published online April 7, 2021
- DOI: https://doi.org/10.4132/jptm.2021.02.22
- 3,774 View
- 155 Download
- 5 Web of Science
- 6 Crossref
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Abstract
PDF
- Programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibition has revolutionized the treatment paradigm of urothelial carcinoma (UC). Several PD-L1 assays are conducted to formulate appropriate treatment decisions for PD-1/PD-L1 target therapy in UC. However, each assay has its own specific requirement of antibody clones, staining platforms, scoring algorithms, and cutoffs for the determination of PD-L1 status. These prove to be challenging constraints to pathology laboratories and pathologists. Thus, the present article comprehensively demonstrates the scoring algorithm used and differences observed in each assay (22C3, SP142, and SP263). Interestingly, the SP142 score algorithm considers only immune cells and not tumor cells (TCs). It remains controversial whether SP142 expressed only in TCs truly accounts for a negative PD-L1 case. Moreover, the scoring algorithm of each assay is complex and divergent, which can result in inter-observer heterogeneity. In this regard, the development of artificial intelligence for providing assistance to pathologists in obtaining more accurate and objective results has been actively researched. To facilitate efficiency of PD-L1 testing, several previous studies attempted to integrate and harmonize each assay in UC. The performance comparison of the various PD-L1 assays demonstrated in previous studies was encouraging, the exceptional concordance rate reported between 22C3 and SP263. Although these two assays may be used interchangeably, a clinically validated algorithm for each agent must be applied.
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Citations
Citations to this article as recorded by- Comparison of tissue biomarkers between non-schistosoma and schistosoma-associated urothelial carcinoma
Nashwah Samir AlHariry, Enas A. El Saftawy, Basma Emad Aboulhoda, Ahmed H. Abozamel, Mansour A. Alghamdi, Amany E. Hamoud, Walaa Abd Elgawad Khalil Ghanam
Tissue and Cell.2024; 88: 102416. CrossRef - Aspectos prácticos sobre la determinación de PD-L1 en el tratamiento de carcinoma urotelial. Consenso del grupo de uropatología de la SEAP
Antonio López-Beltrán, Pilar González-Peramato, Julián Sanz-Ortega, Juan Daniel Prieto Cuadra, Isabel Trias, Rafael J. Luque Barona, María Eugenia Semidey, Pablo Maroto, Ferran Algaba
Revista Española de Patología.2023; 56(4): 261. CrossRef - Systemic treatment of advanced and metastatic urothelial cancer: The landscape in Australia
Howard Gurney, Timothy D. Clay, Niara Oliveira, Shirley Wong, Ben Tran, Carole Harris
Asia-Pacific Journal of Clinical Oncology.2023; 19(6): 585. CrossRef - PD-L1 Testing in Urothelial Carcinoma: Analysis of a Series of 1401 Cases Using Both the 22C3 and SP142 Assays
Harriet Evans, Brendan O’Sullivan, Frances Hughes, Kathryn Charles, Lee Robertson, Philippe Taniere, Salvador Diaz-Cano
Pathology and Oncology Research.2022;[Epub] CrossRef - Insights on recent innovations in bladder cancer immunotherapy
Mohamed A. Abd El‐Salam, Claire E.P. Smith, Chong‐Xian Pan
Cancer Cytopathology.2022; 130(9): 667. CrossRef - What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables
Andrea Palicelli, Martina Bonacini, Stefania Croci, Cristina Magi-Galluzzi, Sofia Cañete-Portillo, Alcides Chaux, Alessandra Bisagni, Eleonora Zanetti, Dario De Biase, Beatrice Melli, Francesca Sanguedolce, Moira Ragazzi, Maria Paola Bonasoni, Alessandra
Cells.2021; 10(11): 3166. CrossRef
- Comparison of tissue biomarkers between non-schistosoma and schistosoma-associated urothelial carcinoma
Original Article
- Programmed death-ligand 1 expression and its correlation with clinicopathological parameters in gallbladder cancer
- Ji Hye Kim, Kyungbin Kim, Misung Kim, Young Min Kim, Jae Hee Suh, Hee Jeong Cha, Hye Jeong Choi
- J Pathol Transl Med. 2020;54(2):154-164. Published online February 10, 2020
- DOI: https://doi.org/10.4132/jptm.2019.11.13
- 7,228 View
- 165 Download
- 14 Web of Science
- 13 Crossref
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Abstract
PDF
- Background
Immunomodulatory therapies targeting the interaction between programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) have become increasingly important in anticancer treatment. Previous research on the subject of this immune response has established an association with tumor aggressiveness and a poor prognosis in certain cancers. Currently, scant information is available on the relationship between PD-L1 expression and gallbladder cancer (GBC).
Methods
We investigated the expression of PD-L1 in 101 primary GBC cases to determine the potential association with prognostic impact. PD-L1 expression was immunohistochemically assessed using a single PD-L1 antibody (clone SP263). Correlations with clinicopathological parameters, overall survival (OS), or progression- free survival (PFS) were analyzed.
Results
PD-L1 expression in tumor cells at cutoff levels of 1%, 10%, and 50% was present in 18.8%, 13.8%, and 7.9% of cases. Our study showed that positive PD-L1 expression at any cutoff was significantly correlated with poorly differentiated histologic grade and the presence of lymphovascular invasion (p < .05). PD-L1 expression at cutoff levels of 10% and 50% was significantly positive in patients with perineural invasion, higher T categories, and higher pathologic stages (p < .05). Additionally, there was a significant association noted between PD-L1 expression at a cutoff level of 50% and worse OS or PFS (p = .049 for OS, p = .028 for PFS). Other poor prognostic factors included histologic grade, T category, N category, pathologic stage, lymphovascular invasion, perineural invasion, growth pattern, and margin of resection (p < .05).
Conclusions
The expression of PD-L1 in GBC varies according to cutoff level but is valuably associated with poor prognostic parameters and survival. Our study indicates that the overexpression of PD-L1 in GBC had a negative prognostic impact. -
Citations
Citations to this article as recorded by- Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis
Giorgio Frega, Fernando P. Cossio, Jesus M. Banales, Vincenzo Cardinale, Rocio I. R. Macias, Chiara Braconi, Angela Lamarca
Cells.2023; 12(16): 2098. CrossRef - Gallbladder carcinomas: review and updates on morphology, immunohistochemistry, and staging
Whayoung Lee, Vishal S. Chandan
Human Pathology.2023; 132: 149. CrossRef - Prognostic Relevance of PDL1 and CA19-9 Expression in Gallbladder Cancer vs. Inflammatory Lesions
Neetu Rawal, Supriya Awasthi, Nihar Ranjan Dash, Sunil Kumar, Prasenjit Das, Amar Ranjan, Anita Chopra, Maroof Ahmad Khan, Sundeep Saluja, Showket Hussain, Pranay Tanwar
Current Oncology.2023; 30(2): 1571. CrossRef - Identification of genes associated with gall bladder cell carcinogenesis: Implications in targeted therapy of gall bladder cancer
Ishita Ghosh, Ruma Dey Ghosh, Soma Mukhopadhyay
World Journal of Gastrointestinal Oncology.2023; 15(12): 2053. CrossRef - CD73 and PD-L1 as Potential Therapeutic Targets in Gallbladder Cancer
Lu Cao, Kim R. Bridle, Ritu Shrestha, Prashanth Prithviraj, Darrell H. G. Crawford, Aparna Jayachandran
International Journal of Molecular Sciences.2022; 23(3): 1565. CrossRef - Evolving Role of Immunotherapy in Advanced Biliary Tract Cancers
Sandra Kang, Bassel F. El-Rayes, Mehmet Akce
Cancers.2022; 14(7): 1748. CrossRef - Novel immune scoring dynamic nomograms based on B7-H3, B7-H4, and HHLA2: Potential prediction in survival and immunotherapeutic efficacy for gallbladder cancer
Chao Lv, Shukun Han, Baokang Wu, Zhiyun Liang, Yang Li, Yizhou Zhang, Qi Lang, Chongli Zhong, Lei Fu, Yang Yu, Feng Xu, Yu Tian
Frontiers in Immunology.2022;[Epub] CrossRef - PD-1 inhibitors plus nab-paclitaxel-containing chemotherapy for advanced gallbladder cancer in a second-line setting: A retrospective analysis of a case series
Sirui Tan, Jing Yu, Qiyue Huang, Nan Zhou, Hongfeng Gou
Frontiers in Oncology.2022;[Epub] CrossRef - Expression of HER2 and Mismatch Repair Proteins in Surgically Resected Gallbladder Adenocarcinoma
You-Na Sung, Sung Joo Kim, Sun-Young Jun, Changhoon Yoo, Kyu-Pyo Kim, Jae Hoon Lee, Dae Wook Hwang, Shin Hwang, Sang Soo Lee, Seung-Mo Hong
Frontiers in Oncology.2021;[Epub] CrossRef - Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer
Thomas Albrecht, Fritz Brinkmann, Michael Albrecht, Anke S. Lonsdorf, Arianeb Mehrabi, Katrin Hoffmann, Yakup Kulu, Alphonse Charbel, Monika N. Vogel, Christian Rupp, Bruno Köhler, Christoph Springfeld, Peter Schirmacher, Stephanie Roessler, Benjamin Goep
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Pallavi A. Patil, Kara Lombardo, Weibiao Cao
Applied Immunohistochemistry & Molecular Morphology.2021; 29(8): 557. CrossRef - Molecular Targets and Emerging Therapies for Advanced Gallbladder Cancer
Matteo Canale, Manlio Monti, Ilario Giovanni Rapposelli, Paola Ulivi, Francesco Giulio Sullo, Giulia Bartolini, Elisa Tiberi, Giovanni Luca Frassineti
Cancers.2021; 13(22): 5671. CrossRef - Overview of current targeted therapy in gallbladder cancer
Xiaoling Song, Yunping Hu, Yongsheng Li, Rong Shao, Fatao Liu, Yingbin Liu
Signal Transduction and Targeted Therapy.2020;[Epub] CrossRef
- Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis
Review
- Tumor immune response and immunotherapy in gastric cancer
- Yoonjin Kwak, An Na Seo, Hee Eun Lee, Hye Seung Lee
- J Pathol Transl Med. 2020;54(1):20-33. Published online November 1, 2019
- DOI: https://doi.org/10.4132/jptm.2019.10.08
- 13,797 View
- 738 Download
- 61 Web of Science
- 57 Crossref
-
Abstract
PDF
- Remarkable developments in immuno-oncology have changed the landscape of gastric cancer (GC) treatment. Because immunotherapy intervenes with tumor immune response rather than directly targeting tumor cells, it is important to develop a greater understanding of tumor immunity. This review paper summarizes the tumor immune reaction and immune escape mechanisms while focusing on the role of T cells and their co-inhibitory signals, such as the immune checkpoint molecules programmed death-1 and programmed deathligand 1 (PD-L1). This paper also describes past clinical trials of immunotherapy for patients with GC and details their clinical implications. Strong predictive markers are essential to improve response to immunotherapy. Microsatellite instability, Epstein-Barr virus, PD-L1 expression, and tumor mutational burden are now regarded as potent predictive markers for immunotherapy in patients with GC. Novel immunotherapy and combination therapy targeting new immune checkpoint molecules such as lymphocyte-activation gene 3, T cell immunoglobulin, and mucin domain containing-3, and indoleamine 2,3-dioxygenase have been suggested, and trials are ongoing to evaluate their safety and efficacy. Immunotherapy is an important treatment option for patients with GC and has great potential for improving patient outcome, and further research in immuno-oncology should be carried out.
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Citations
Citations to this article as recorded by- Ubiquilin-4 induces immune escape in gastric cancer by activating the notch signaling pathway
Quan Jiang, Hao Chen, Shixin Zhou, Tao Zhu, Wenshuai Liu, Hao Wu, Yong Zhang, Fenglin Liu, Yihong Sun
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Chenchen Wang, Ying Chen, Ru Zhou, Ya’nan Yang, Yantian Fang
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Journal of Biochemical and Molecular Toxicology.2021;[Epub] CrossRef - Prognostic Value of C-Reactive Protein to Albumin Ratio in Gastric Cancer: A Meta-Analysis
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Original Article
- Interobserver Reproducibility of PD-L1 Biomarker in Non-small Cell Lung Cancer: A Multi-Institutional Study by 27 Pathologists
- Sunhee Chang, Hyung Kyu Park, Yoon-La Choi, Se Jin Jang
- J Pathol Transl Med. 2019;53(6):347-353. Published online October 28, 2019
- DOI: https://doi.org/10.4132/jptm.2019.09.29
- 5,763 View
- 205 Download
- 28 Web of Science
- 27 Crossref
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Abstract
PDF
- Background
Assessment of programmed cell death-ligand 1 (PD-L1) immunohistochemical staining is used for treatment decisions in non-small cell lung cancer (NSCLC) regarding use of PD-L1/programmed cell death protein 1 (PD-1) immunotherapy. The reliability of the PD-L1 22C3 pharmDx assay is critical in guiding clinical practice. The Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists investigated the interobserver reproducibility of PD-L1 staining with 22C3 pharmDx in NSCLC samples.
Methods
Twenty-seven pathologists individually assessed the tumor proportion score (TPS) for 107 NSCLC samples. Each case was divided into three levels based on TPS: <1%, 1%–49%, and ≥50%.
Results
The intraclass correlation coefficient for TPS was 0.902±0.058. Weighted κ coefficient for 3-step assessment was 0.748±0.093. The κ coefficients for 1% and 50% cut-offs were 0.633 and 0.834, respectively. There was a significant association between interobserver reproducibility and experience (formal PD-L1 training, more experience for PD-L1 assessment, and longer practice duration on surgical pathology), histologic subtype, and specimen type.
Conclusions
Our results indicate that PD-L1 immunohistochemical staining provides a reproducible basis for decisions on anti–PD-1 therapy in NSCLC. -
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Review
- PD-L1 Testing in Non-small Cell Lung Cancer: Past, Present, and Future
- Hyojin Kim, Jin-Haeng Chung
- J Pathol Transl Med. 2019;53(4):199-206. Published online May 2, 2019
- DOI: https://doi.org/10.4132/jptm.2019.04.24
- Correction in: J Pathol Transl Med 2020;54(2):196
- 14,773 View
- 637 Download
- 62 Web of Science
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Abstract
PDF
- Blockade of the programmed cell death-1 (PD-1) axis has already been established as an effective treatment of non-small cell lung cancer. Immunohistochemistry (IHC) for programmed death-ligand 1 (PD-L1) protein is the only available biomarker that can guide treatment with immune checkpoint inhibitors in non-small cell lung cancer. Because each PD-1/PD-L1 blockade was approved together with a specific PD-L1 IHC assay used in the clinical trials, pathologists have been challenged with performing various assays with a limited sample. To provide a more unified understanding of this, several cross-validation studies between platforms have been performed and showed consistent results. However, the interchangeability of assays may be limited in practice because of the risk of misclassification of patients for the treatment. Furthermore, several issues, including the temporal and spatial heterogeneity of PD-L1 expression in the tumor, and the potential for cytology specimens to be used as an alternative to tissue samples for PD-L1 testing, have still not been resolved. In the future, one of the main aims of immunotherapy research should be to find a novel predictive biomarker for PD-1 blockade therapy and a way to combine it with PD-L1 IHC and other tests.
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Original Articles
- Human Leukocyte Antigen Class I and Programmed Death-Ligand 1 Coexpression Is an Independent Poor Prognostic Factor in Adenocarcinoma of the Lung
- Yeon Bi Han, Hyun Jung Kwon, Soo Young Park, Eun-Sun Kim, Hyojin Kim, Jin-Haeng Chung
- J Pathol Transl Med. 2019;53(2):86-93. Published online January 14, 2019
- DOI: https://doi.org/10.4132/jptm.2018.12.26
- 5,752 View
- 133 Download
- 4 Web of Science
- 3 Crossref
-
Abstract
PDF
- Background
Both human leukocyte antigen (HLA) class I and programmed death-ligand 1 (PD-L1) molecules are known to play important roles in cancer immunity. In this study, we evaluated HLA class I expression in resected adenocarcinoma of the lung, and investigated its prognostic impact in correlation with PD-L1 expression.
Methods
HLA class I and PD-L1 expression was evaluated by immunohistochemistry in a total of 403 resected lung adenocarcinomas using tissue microarray. Correlations between the expression of HLA class I/PD-L1 and clinicopathologic features and prognostic significance were analyzed.
Results
HLA class I expression was reduced in 91.6% of adenocarcinoma, and more frequently reduced in patients with younger age, absence of vascular invasion, and low pathologic stage (p = .033, p = .007, and p = .012, respectively). Positive PD-L1 expression in tumor cells was 16.1% (1% cut-off), and associated with poor differentiation, presence of vascular invasion and nodal metastasis (p < .001, p = .002, and p = .032, respectively). On survival analysis, HLA class I or PD-L1 expression alone did not show any statistical significance. On the integrated analysis, HLA class I (+)/PD-L1 (+) subgroup showed a significantly shorter overall survival than other groups (p = .001). Multivariate analysis revealed that coexpression of HLA class I and PD-L1 was an independent poor prognostic factor of lung adenocarcinoma. (p < .001; hazard ratio, 6.106; 95% confidence interval, 2.260 to 16.501).
Conclusions
Lung adenocarcinoma with coexpression of HLA class I and PD-L1 was associated with poor prognosis. This subgroup may evade immune attack by expressing PD-L1 protein despite HLA expression. -
Citations
Citations to this article as recorded by- Assessment of cancer cell‐expressed HLA class I molecules and their immunopathological implications
Terufumi Kubo, Shiori Asano, Kenta Sasaki, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Toshihiko Torigoe
HLA.2024;[Epub] 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 - Loss of HLA-class-I expression in non-small-cell lung cancer: Association with prognosis and anaerobic metabolism
Ioannis M. Koukourakis, Alexandra Giatromanolaki, Achilleas Mitrakas, Michael I. Koukourakis
Cellular Immunology.2022; 373: 104495. CrossRef
- Assessment of cancer cell‐expressed HLA class I molecules and their immunopathological implications
- Programmed Death-Ligand 1 Expression and Its Correlation with Lymph Node Metastasis in Papillary Thyroid Carcinoma
- Hyo Jung An, Gyung Hyuck Ko, Jeong-Hee Lee, Jong Sil Lee, Dong Chul Kim, Jung Wook Yang, Min Hye Kim, Jin Pyeong Kim, Eun Jung Jung, Dae Hyun Song
- J Pathol Transl Med. 2018;52(1):9-13. Published online October 3, 2017
- DOI: https://doi.org/10.4132/jptm.2017.07.26
- 8,563 View
- 278 Download
- 17 Web of Science
- 14 Crossref
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Abstract
PDF
- Background
The immunotherapeutic role of programmed death-ligand 1 (PD-L1) in life expectancy in many cancers has been highlighted. However, data regarding PD-L1 expression in papillary thyroid carcinoma (PTC) are limited. In this study, we describe the PD-L1 and programmed cell death protein 1 (PD-1) expressions in PTC and analyze their correlation with lymph node (LN) metastasis.
Methods
Clinicopathological data were obtained from 116 patients with PTC who were treated in Gyeongsang National University Hospital, Jinju, Korea in 2009. Tissue microarray blocks were made using representative paraffin blocks of classical PTCs excluding follicular variants. Two pathologists graded the proportion and intensity of PD-L1 and PD-1 expression in both tumor and inflammatory cells. According to their proportions, positive PTC cells were scored as negative (0%), grade 1 (1%–50%), and grade 2 (51%–100%). Similarly, positive inflammatory cells were graded as negative (0%), grade 1 (1%–10%), and grade 2 (11%–20%). The intensity of each protein expression was simplified as positive or negative.
Results
A statistically significant correlation exists between the proportions of PD-1 and PD-L1 expression both in papillary carcinoma (p=.001) and peritumoral lymphoid cells in the thyroid (p<.001). In addition, the proportion of PD-L1 expression in PTC cells was closely related to metastatic LNs (p=.036).
Conclusions
PD-L1 is a valuable predictive marker for LN metastasis in PTC. Immunomodulating therapies that inhibit PD-L1 might be an option for patients with LN metastasis. -
Citations
Citations to this article as recorded by- Chronic Lymphocytic Thyroiditis with Oncocytic Metaplasia Influences PD-L1 Expression in Papillary Thyroid Carcinoma
Vitor Barreto Santana, Vitória Machado Krüger, Maria Cristina Yunes Abrahão, Pietru Lentz Martins Cantú, Rosicler Luzia Brackmann, Gisele Moroni Pandolfi, Liane Scheffler Marisco, Gabriela Remonatto, Luciana Adolfo Ferreira, Marcia Silveira Graudenz
Head and Neck Pathology.2024;[Epub] CrossRef - Exploring markers of immunoresponsiveness in papillary thyroid carcinoma and future treatment strategies
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Journal for ImmunoTherapy of Cancer.2024; 12(7): e008505. CrossRef - Update regarding the role of PD-L1 in oncocytic thyroid lesions on cytological samples
Marco Dell'Aquila, Pietro Tralongo, Alessia Granitto, Maurizio Martini, Sara Capodimonti, Mariangela Curatolo, Vincenzo Fiorentino, Alfredo Pontecorvi, Guido Fadda, Celestino Pio Lombardi, Maco Raffaelli, Liron Pantanowitz, Luigi Maria Larocca, Esther Dia
Journal of Clinical Pathology.2023; 76(10): 671. CrossRef - Analysis of anti‐apoptotic PVT1 oncogene and apoptosis‐related proteins (p53, Bcl2, PD‐1, and PD‐L1) expression in thyroid carcinoma
Afaf T. Ibrahiem, Amin K. Makhdoom, Khalid S. Alanazi, Abdulaziz M. Alanazi, Abdulaziz M. Mukhlef, Saad H. Elshafey, Eman A. Toraih, Manal S. Fawzy
Journal of Clinical Laboratory Analysis.2022;[Epub] CrossRef - EphA10 drives tumor progression and immune evasion by regulating the MAPK/ERK cascade in lung adenocarcinoma
Wenyue Zhao, Lu Liu, Xuehao Li, Shun Xu
International Immunopharmacology.2022; 110: 109031. CrossRef - Hashimoto’s Thyroiditis Minimizes Lymph Node Metastasis in BRAF Mutant Papillary Thyroid Carcinomas
Peter P. Issa, Mahmoud Omar, Yusef Buti, Chad P. Issa, Bert Chabot, Christopher J. Carnabatu, Ruhul Munshi, Mohammad Hussein, Mohamed Aboueisha, Mohamed Shama, Ralph L. Corsetti, Eman Toraih, Emad Kandil
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Mohamed Sherif Ismail, Amr Mousa Abdel Gawad Mousa, Mohammed Faisal Darwish, M. Mostafa Salem, Randa Said
Open Access Macedonian Journal of Medical Sciences.2022; 10(A): 1565. CrossRef - Identification and validation of an immune-related prognostic signature and key gene in papillary thyroid carcinoma
Rujia Qin, Chunyan Li, Xuemin Wang, Zhaoming Zhong, Chuanzheng Sun
Cancer Cell International.2021;[Epub] CrossRef - PD‐L1 and thyroid cytology: A possible diagnostic and prognostic marker
Marco Dell’Aquila, Alessia Granitto, Maurizio Martini, Sara Capodimonti, Alessandra Cocomazzi, Teresa Musarra, Vincenzo Fiorentino, Alfredo Pontecorvi, Celestino Pio Lombardi, Guido Fadda, Liron Pantanowitz, Luigi Maria Larocca, Esther Diana Rossi
Cancer Cytopathology.2020; 128(3): 177. CrossRef - Programmed Death-Ligand 1 (PD-L1) Is a Potential Biomarker of Disease-Free Survival in Papillary Thyroid Carcinoma: a Systematic Review and Meta-Analysis of PD-L1 Immunoexpression in Follicular Epithelial Derived Thyroid Carcinoma
Ilaria Girolami, Liron Pantanowitz, Ozgur Mete, Matteo Brunelli, Stefano Marletta, Chiara Colato, Pierpaolo Trimboli, Anna Crescenzi, Massimo Bongiovanni, Mattia Barbareschi, Albino Eccher
Endocrine Pathology.2020; 31(3): 291. CrossRef - Regression of Papillary Thyroid Cancer during Nivolumab for Renal Cell Cancer
Andrea Palermo, Andrea Napolitano, Daria Maggi, Anda Mihaela Naciu, Gaia Tabacco, Silvia Manfrini, Anna Crescenzi, Chiara Taffon, Francesco Pantano, Bruno Vincenzi, Guiseppe Tonini, Daniele Santini
European Thyroid Journal.2020; 9(3): 157. CrossRef - A potential biomarker hsa-miR-200a-5p distinguishing between benign thyroid tumors with papillary hyperplasia and papillary thyroid carcinoma
Xian Wang, Shan Huang, Xiaocan Li, Dongrui Jiang, Hongzhen Yu, Qiang Wu, Chaobing Gao, Zhengsheng Wu, Yi-Hsien Hsieh
PLOS ONE.2018; 13(7): e0200290. CrossRef - Papillary Thyroid Carcinoma Emerging from Hashimoto Thyroiditis Demonstrates Increased PD-L1 Expression, Which Persists with Metastasis
Daniel Lubin, Ezra Baraban, Amanda Lisby, Sahar Jalali-Farahani, Paul Zhang, Virginia Livolsi
Endocrine Pathology.2018; 29(4): 317. CrossRef - Chemotherapeutic Treatments Increase PD-L1 Expression in Esophageal Squamous Cell Carcinoma through EGFR/ERK Activation
Hoi Yan Ng, Jian Li, Lihua Tao, Alfred King-Yin Lam, Kwok Wah Chan, Josephine Mun Yee Ko, Valen Zhuoyou Yu, Michael Wong, Benjamin Li, Maria Li Lung
Translational Oncology.2018; 11(6): 1323. CrossRef
- Chronic Lymphocytic Thyroiditis with Oncocytic Metaplasia Influences PD-L1 Expression in Papillary Thyroid Carcinoma
- GLUT1 as a Prognostic Factor for Classical Hodgkin’s Lymphoma: Correlation with PD-L1 and PD-L2 Expression
- Young Wha Koh, Jae-Ho Han, Seong Yong Park, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh
- J Pathol Transl Med. 2017;51(2):152-158. Published online February 21, 2017
- DOI: https://doi.org/10.4132/jptm.2016.11.03
- 9,188 View
- 234 Download
- 19 Web of Science
- 18 Crossref
-
Abstract
PDF
- Background
Glucose transporter type 1 (GLUT1) expression is linked to glucose metabolism and tissue hypoxia. A recent study reported that GLUT1 was significantly associated with programmed death ligand 1 (PD-L1) as a therapeutic target in relapsed or refractory classical Hodgkin’s lymphoma (cHL). The purpose of this study was to measure the expression of GLUT1 and assess its prognostic significance and potential relationships with PD-L1, programmed death ligand 2 (PD-L2), and programmed death-1 (PD-1) expressions in cHL. Methods: Diagnostic tissues from 125 patients with cHL treated with doxorubicin, bleomycin, vinblastine, and dacarbazine were evaluated retrospectively via immunohistochemical analysis of GLUT1, PD-L1, PD-L2, and PD-1 expression. Results: The median follow-up time was 4.83 years (range, 0.08 to 17.33 years). GLUT1, PD-L1, PD-L2, and PD-1 were expressed in 44.8%, 63.2%, 9.6%, and 13.6% of the specimens, respectively. Positive correlations were found between GLUT1 and PD-L1 expression (p = .004) and between GLUT1 and PD-L2 expression (p = .031). GLUT1 expression in Hodgkin/Reed-Sternberg (HRS) cells was not associated with overall survival or event-free survival (EFS) in the entire cohort (p = .299 and p = .143, respectively). A subgroup analysis according to the Ann Arbor stage illustrated that GLUT1 expression in HRS cells was associated with better EFS in advanced-stage disease (p = .029). A multivariate analysis identified GLUT1 as a marginally significant prognostic factor for EFS (p = .068). Conclusions: This study suggests that GLUT1 expression is associated with better clinical outcomes in advanced-stage cHL and is significantly associated with PD-L1 and PD-L2 expressions. -
Citations
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Barbara Marengo, Ombretta Garbarino, Andrea Speciale, Lorenzo Monteleone, Nicola Traverso, Cinzia Domenicotti
Oxidative Medicine and Cellular Longevity.2019; 2019: 1. CrossRef - Sustain, Adapt, and Overcome—Hypoxia Associated Changes in the Progression of Lymphatic Neoplasia
Orsolya Matolay, Gábor Méhes
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- PD-L1 Expression and Combined Status of PD-L1/PD-1–Positive Tumor Infiltrating Mononuclear Cell Density Predict Prognosis in Glioblastoma Patients
- Jiheun Han, Yongkil Hong, Youn Soo Lee
- J Pathol Transl Med. 2017;51(1):40-48. Published online December 15, 2016
- DOI: https://doi.org/10.4132/jptm.2016.08.31
- 13,944 View
- 275 Download
- 32 Web of Science
- 34 Crossref
-
Abstract
PDF
- Background
Programmed death ligand 1 (PD-L1) in tumor cells is known to promote immune escape of cancer by interacting with programmed cell death 1 (PD-1) in tumor infiltrating immune cells. Immunotherapy targeting these molecules is emerging as a new strategy for the treatment of glioblastoma (GBM). Understanding the relationship between the PD-L1/PD-1 axis and prognosis in GBM patients may be helpful to predict the effects of immunotherapy.
Methods
PD-L1 expression and PD-1–positive tumor infiltrating mononuclear cell (PD-1+tumor infiltrating mononuclear cell [TIMC]) density were evaluated using tissue microarray containing 54 GBM cases by immunohistochemical analysis; the associations with patient clinical outcomes were evaluated.
Results
PD-L1 expression and high PD-1+TIMC density were observed in 31.5% and 50% of GBM cases, respectively. High expression of PD-L1 in tumor cells was an independent and significant predictive factor for worse overall survival (OS; hazard ratio, 4.958; p = .007) but was not a significant factor in disease-free survival (DFS). PD-1+TIMC density was not correlated with OS or DFS. When patients were classified based on PD-1 expression and PD-1+TIMC density, patients with PD-L1+/PD-1+TIMC low status had the shortest OS (13 months, p = .009) and DFS (7 months, p = .053).
Conclusions
PD-L1 expression in GBM was an independent prognostic factor for poor OS. In addition, combined status of PD-L1 expression and PD-1+TIMC density also predicted patient outcomes, suggesting that the therapeutic role of the PD-1/PD-L1 axis should be considered in the context of GBM immunity. -
Citations
Citations to this article as recorded by- Tumor-associated microenvironment, PD-L1 expression and their relationship with immunotherapy in glioblastoma, IDH-wild type: A comprehensive review with emphasis on the implications for neuropathologists
Giuseppe Broggi, Giuseppe Angelico, Jessica Farina, Giordana Tinnirello, Valeria Barresi, Magda Zanelli, Andrea Palicelli, Francesco Certo, Giuseppe Barbagallo, Gaetano Magro, Rosario Caltabiano
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Berta Segura-Collar, Sara Hiller-Vallina, Olaya de Dios, Marta Caamaño-Moreno, Lucia Mondejar-Ruescas, Juan M. Sepulveda-Sanchez, Ricardo Gargini
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- Aberrant Blood Vessel Formation Connecting the Glomerular Capillary Tuft and the Interstitium Is a Characteristic Feature of Focal Segmental Glomerulosclerosis-like IgA Nephropathy
- Beom Jin Lim, Min Ju Kim, Soon Won Hong, Hyeon Joo Jeong
- J Pathol Transl Med. 2016;50(3):211-216. Published online April 11, 2016
- DOI: https://doi.org/10.4132/jptm.2016.02.01
- 7,712 View
- 72 Download
- 1 Web of Science
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Abstract
PDF
- Background
Segmental glomerulosclerosis without significant mesangial or endocapillary proliferation is rarely seen in IgA nephropathy (IgAN), which simulates idiopathic focal segmental glomerulosclerosis (FSGS). We recently recognized aberrant blood vessels running through the adhesion sites of sclerosed tufts and Bowman’s capsule in IgAN cases with mild glomerular histologic change.
Methods
To characterize aberrant blood vessels in relation to segmental sclerosis, we retrospectively reviewed the clinical and histologic features of 51 cases of FSGS-like IgAN and compared them with 51 age and gender-matched idiopathic FSGS cases.
Results
In FSGS-like IgAN, aberrant blood vessel formation was observed in 15.7% of cases, 1.0% of the total glomeruli, and 7.3% of the segmentally sclerosed glomeruli, significantly more frequently than in the idiopathic FSGS cases (p = .009). Aberrant blood vessels occasionally accompanied mild cellular proliferation surrounding penetrating neovessels. Clinically, all FSGS-like IgAN cases had hematuria; however, nephrotic range proteinuria was significantly less frequent than idiopathic FSGS.
Conclusions
Aberrant blood vessels in IgAN are related to glomerular capillary injury and may indicate abnormal repair processes in IgAN. -
Citations
Citations to this article as recorded by- IgA nephropathy
Maria F. Soares, Ian S.D. Roberts
Current Opinion in Nephrology and Hypertension.2017; 26(3): 165. CrossRef
- IgA nephropathy
- IgA Nephropathy: Correlation of WHO Classification and Morphologic Semi-quantitative Scoring System.
- Kyung Jin Seo, Tae Jung Kim, Kyo Young Lee, Sang In Shim, Yeong Jin Choi
- Korean J Pathol. 2009;43(3):244-249.
- DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.244
- 3,467 View
- 45 Download
- 1 Crossref
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Abstract
PDF
- BACKGROUND
IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, and the clinical course of IgAN shows marked variability. Many efforts have made to histologically predict the clinical outcome. There are two methods to classify IgAN. One is mainly based on the glomerular changes, such as the WHO and the Lee and Haas classification systems. The other is a morphologic semi-quantitative scoring system, which counts the changes of the glomerular, tubulointerstitial and vascular structures, respectively. The purpose of this study is to determine whether the WHO classification properly reflects the various morphologic findings of IgAN.
METHODS
We analyzed 354 cases of IgAN by both the WHO classification system and the semiquantitative scoring system and evaluated the correlations of these two methods.
RESULTS
The severity of the glomerular lesions (glomerulosclerosis, capsular adhesion and mesangial matrix expansion) and the tubulointerstitial lesions (interstitial fibrosis, tubular atrophy and interstitial lymphocytic infiltration) are strongly correlated with the increase of the WHO classes of IgAN (Spearman's rho [R] > or =0.5, p<0.05). There is a weak correlation between crescent formation and the increase of the WHO classes (R=0.3, p<0.05).
CONCLUSIONS
This study shows that the WHO classification well reflects the severity of various morphologic findings and this suggests a complementary role for the semi-quantitative scoring system in classifying IgAN. -
Citations
Citations to this article as recorded by- The Oxford classification as a predictor of prognosis in patients with IgA nephropathy
S. H. Kang, S. R. Choi, H. S. Park, J. Y. Lee, I. O. Sun, H. S. Hwang, B. H. Chung, C. W. Park, C. W. Yang, Y. S. Kim, Y. J. Choi, B. S. Choi
Nephrology Dialysis Transplantation.2012; 27(1): 252. CrossRef
- The Oxford classification as a predictor of prognosis in patients with IgA nephropathy
- Significance of Ultrastructural Electron Dense Deposits on Glomerular Capillary Loops in IgA Nephropathy.
- Sun Hee Sung, Ok Kyung Kim, Woon Sup Han
- Korean J Pathol. 1996;30(1):32-39.
- 1,794 View
- 28 Download
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Abstract
PDF
- To evaluate the clinical and histopathological significance of electron dense deposits on capillary in IgA nephropathy, we reviewed and compared the clinical, laboratory, and pathological features of the patients with IgA nephropathy without loop extension of electron dense deposits(Group I, 91 cases) and IgA nephropathy with loop extension(Group II, 17cases) by ultrastructural examination using transmission electron microscope. IgA nephropathy associated with liver disease, Henoch-Schonlein purpura, systemic lupus erythematosus and the other IgA nephropathies associated with systemic diseases were excluded. The results were as follows; 1) There was no significant difference in age distribution. 2) Generalized edema was more common in group II. 3) Nephrotic ranged proteinuria(>3 g/24hr urine) was more prominent in Group II(52.9%) than Group I(8.8%). 4) Among the groups, segmental or mild deposits on the loops were noted in 13 cases, and severe and generalized deposits in 4 cases. Subendothelial deposits were noted in 6 cases, subepithelial deposits in 3 cases, subendothelial with intramembranous deposits in 1 case, subendothelial with subepithelial deposits in 1 case, intramembranous with subepithelial deposits in 2 cases, and subendothelial, subepithelial and intramembranous deposits in 4 cases. 5) The other associated ultrastructural changes of group II were diffuse effacement of foot processes with microvillous transformation, swelling or vacuolar degeneration of podocytes and glomerular endothelium. 6) According to the WHO morphologic criteria, the grade of Group II was significantly higher than Group I. From the above results, it can be concluded that the extension of electron dense deposits along the capillary loops in the cases of IgA nephropathy is highly correlated with proteinuria in the nephrotic ranged. It seems to be a poor prognostic indicator in view of the facts that it correlats with high histopathologic grading.
- Ultrastructural Changes of the Bile Canaliculi after Common Bile Duct Ligation.
- Kook Seon Yoo, Suk Hee Lee, Hee Kyung Park, Chang Ho Cho, Jong Min Chae
- Korean J Pathol. 1996;30(3):175-183.
- 1,824 View
- 28 Download
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Abstract
PDF
- The purpose of this study was to investigate the morphologic changes of the bile canaliculi and its associated structures of the liver induced by common bile duct ligation(CBDL) in the rat. The canalicular surface and lateral surface of the dry-fractured hepatocytes was studied with scanning electron microscopy at 1~6 weeks post ligation. The first week after CBDL, the bile canaliculi were dilated. The microvilli were increased in number and the lumens contained granular materials After 2 weeks or more, the bile canaliculi were dilated to a variable degree, and with irregularity, measuring from 1.5 to 5 micrometer in diameter, and in the advanced stage, the canaliculi showed blunting and the disappearance of microvilli. Some canaliculi had sprouting side branches. At 4~6 weeks post-ligation, the lateral surface of the hepatocytes also showed some irregularity and a tortuous appearance, and numerous small sized microvillous projections were formed. The tubular structures of the proliferated SER distributed adjacent to the lateral surface of the hepatocytes, and the direct connection of a tubular structure and the cytoplasmic membrane was observed. These results suggest that the deformity and loss of microvilli of bile canaliculi reflect the disturbance of bile secretion from the hepatocytes. And prolonged obstruction of bile flow may result in bile excretion via the lateral surface of hepatocytes.
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