Journal of Pathology and Translational Medicine

Kyoungyul Lee

3 Articles

Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists: Soomin Ahn, Yoonjin Kwak, Gui Young Kwon, Kyoung-Mee Kim, Moonsik Kim, Hyunki Kim, Young Soo Park, Hyeon Jeong Oh, Kyoungyul Lee, Sung Hak Lee, Hye Seung Lee; J Pathol Transl Med. 2024;58(3):103-116. Published online April 25, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.15

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Nivolumab plus chemotherapy in the first-line setting has demonstrated clinical efficacy in patients with human epidermal growth factor receptor 2–negative advanced or metastatic gastric cancer, and is currently indicated as a standard treatment. Programmed death-ligand 1 (PD-L1) expression is an important biomarker for predicting response to anti–programmed death 1/PD-L1 agents in several solid tumors, including gastric cancer. In the CheckMate-649 trial, significant clinical improvements were observed in patients with PD-L1 combined positive score (CPS) ≥ 5, determined using the 28-8 pharmDx assay. Accordingly, an accurate interpretation of PD-L1 CPS, especially at a cutoff of 5, is important. The CPS method evaluates both immune and tumor cells and provides a comprehensive assessment of PD-L1 expression in the tumor microenvironment of gastric cancer. However, CPS evaluation has several limitations, one of which is poor interobserver concordance among pathologists. Despite these limitations, clinical indications relying on PD-L1 CPS are increasing. In response, Korean gastrointestinal pathologists held a consensus meeting for the interpretation of PD-L1 CPS in gastric cancer. Eleven pathologists reviewed 20 PD-L1 slides with a CPS cutoff close to 5, stained with the 28-8 pharmDx assay, and determined the consensus scores. The issues observed in discrepant cases were discussed. In this review, we present cases of gastric cancer with consensus PD-L1 CPS. In addition, we briefly touch upon current practices and clinical issues associated with assays used for the assessment of PD-L1 expression in gastric cancer.

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Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIG
F. Lordick, M.E. Mauer, G. Stocker, C.A. Cella, I. Ben-Aharon, G. Piessen, L. Wyrwicz, G. Al-Haidari, T. Fleitas-Kanonnikoff, V. Boige, R. Lordick Obermannová, U.M. Martens, C. Gomez-Martin, P. Thuss-Patience, V. Arrazubi, A. Avallone, K.K. Shiu, P. Artru
Annals of Oncology.2025; 36(2): 197. CrossRef
PD-L1 as a Biomarker in Gastric Cancer Immunotherapy
Yunjoo Cho, Soomin Ahn, Kyoung-Mee Kim
Journal of Gastric Cancer.2025; 25(1): 177. CrossRef
PD-L1 importance in malignancies comprehensive insights into the role of PD-L1 in malignancies: from molecular mechanisms to therapeutic opportunities
Mojdeh Soltani, Mohammad Abbaszadeh, Hamed Fouladseresht, Mark J. M. Sullman, Nahid Eskandari
Clinical and Experimental Medicine.2025;[Epub] CrossRef
PD-L1 thresholds predict efficacy of immune checkpoint inhibition in first-line treatment of advanced gastroesophageal adenocarcinoma. A systematic review and meta-analysis of seven phase III randomized trials
V. Formica, C. Morelli, L. Fornaro, S. Riondino, M. Rofei, E. Fontana, E.C. Smyth, M. Roselli, H.-T. Arkenau
ESMO Open.2024; 9(11): 103967. CrossRef

HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation: Soomin Ahn, Ji Won Woo, Kyoungyul Lee, So Yeon Park; J Pathol Transl Med. 2020;54(1):34-44. Published online November 6, 2019; DOI: https://doi.org/10.4132/jptm.2019.11.03

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Abstract PDF

Human epidermal growth factor receptor 2 (HER2) protein overexpression and/or HER2 gene amplification is found in about 20% of invasive breast cancers. It is a sole predictive marker for treatment benefits from HER2 targeted therapy and thus, HER2 testing is a routine practice for newly diagnosed breast cancer in pathology. Currently, HER2 immunohistochemistry (IHC) is used for a screening test, and in situ hybridization is used as a confirmation test for HER2 IHC equivocal cases. Since the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines on HER2 testing was first released in 2007, it has been updated to provide clear instructions for HER2 testing and accurate determination of HER2 status in breast cancer. During HER2 interpretation, some pitfalls such as intratumoral HER2 heterogeneity and increase in chromosome enumeration probe 17 signals may lead to inaccurate assessment of HER2 status. Moreover, HER2 status can be altered after neoadjuvant chemotherapy or during metastatic progression, due to biologic or methodologic issues. This review addresses recent updates of ASCO/CAP guidelines and factors complicating in the interpretation of HER2 status in breast cancers.

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Aquaporin 1 Is an Independent Marker of Poor Prognosis in Lung Adenocarcinoma: Sumi Yun, Ping-Li Sun, Yan Jin, Hyojin Kim, Eunhyang Park, Soo Young Park, Kyuho Lee, Kyoungyul Lee, Jin-Haeng Chung; J Pathol Transl Med. 2016;50(4):251-257. Published online June 7, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.30

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Abstract PDF

Background
Aquaporin 1 (AQP1) overexpression has been shown to be associated with uncontrolled cell replication, invasion, migration, and tumor metastasis. We aimed to evaluate AQP1 expression in lung adenocarcinomas and to examine its association with clinicopathological features and prognostic significance. We also investigated the association between AQP1 overexpression and epithelial-mesenchymal transition (EMT) markers.
Methods
We examined AQP1 expression in 505 cases of surgically resected lung adenocarcinomas acquired at the Seoul National University Bundang Hospital from 2003 to 2012. Expression of AQP1 and EMT-related markers, including Ecadherin and vimentin, were analyzed by immunohistochemistry and tissue microarray.
Results
AQP1 overexpression was associated with several aggressive pathological parameters, including venous invasion, lymphatic invasion, and tumor recurrence. AQP1 overexpression tended to be associated with higher histological grade, advanced pathological stage, and anaplastic lymphoma kinase (ALK) translocation; however, these differences were not statistically significant. In addition, AQP1 overexpression positively correlated with loss of E-cadherin expression and acquired expression of vimentin. Lung adenocarcinoma patients with AQP1 overexpression showed shorter progression- free survival (PFS, 46.1 months vs. 56.2 months) compared to patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter PFS (hazard ratio, 1.429; 95% confidence interval, 1.033 to 1.977; p=.031).
Conclusions
AQP1 overexpression was thereby concluded to be an independent factor of poor prognosis associated with shorter PFS in lung adenocarcinoma. These results suggested that AQP1 overexpression might be considered as a prognostic biomarker of lung adenocarcinoma.

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A Comprehensive Prognostic Analysis of Tumor-Related Blood Group Antigens in Pan-Cancers Suggests That SEMA7A as a Novel Biomarker in Kidney Renal Clear Cell Carcinoma
Yange Wang, Chenyang Li, Xinlei Qi, Yafei Yao, Lu Zhang, Guosen Zhang, Longxiang Xie, Qiang Wang, Wan Zhu, Xiangqian Guo
International Journal of Molecular Sciences.2022; 23(15): 8799. CrossRef
Differential modulation of lung aquaporins among other pathophysiological markers in acute (Cl2 gas) and chronic (carbon nanoparticles, cigarette smoke) respiratory toxicity mouse models
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Frontiers in Physiology.2022;[Epub] CrossRef
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Sarannya Edamana, Frédéric H. Login, Soichiro Yamada, Tae-Hwan Kwon, Lene N. Nejsum
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Comprehensive Analysis of Aquaporin Superfamily in Lung Adenocarcinoma
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Frontiers in Molecular Biosciences.2021;[Epub] CrossRef
Diagnostic accuracy of urinary aquaporin-1 as a biomarker for renal cell carcinoma
Abhilash Cheriyan, Arun Jose Nellickal, Nirmal Thampi John, Lakshmanan Jeyaseelan, Santosh Kumar, Antony Devasia, Nitin Kekre
Indian Journal of Urology.2021; 37(1): 59. CrossRef
Aquaporin 1, 3, and 5 Patterns in Salivary Gland Mucoepidermoid Carcinoma: Expression in Surgical Specimens and an In Vitro Pilot Study
Mérin Barbara Stamboni, Ágatha Nagli de Mello Gomes, Milena Monteiro de Souza, Katia Klug Oliveira, Claudia Fabiana Joca Arruda, Fernanda de Paula, Barbara Beltrame Bettim, Márcia Martins Marques, Luiz Paulo Kowalski, Clóvis Antônio Lopes Pinto, Victor El
International Journal of Molecular Sciences.2020; 21(4): 1287. CrossRef
Combined Systematic Review and Transcriptomic Analyses of Mammalian Aquaporin Classes 1 to 10 as Biomarkers and Prognostic Indicators in Diverse Cancers
Pak Hin Chow, Joanne Bowen, Andrea J Yool
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Aquaporins in lung health and disease: Emerging roles, regulation, and clinical implications
Ekta Yadav, Niket Yadav, Ariel Hus, Jagjit S. Yadav
Respiratory Medicine.2020; 174: 106193. CrossRef
Dissecting gene‐environment interactions: A penalized robust approach accounting for hierarchical structures
Cen Wu, Yu Jiang, Jie Ren, Yuehua Cui, Shuangge Ma
Statistics in Medicine.2018; 37(3): 437. CrossRef
Immunohistochemical Expression of Aquaporin-1 in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Report
Giuseppe Angelico, Rosario Caltabiano, Carla Loreto, Antonio Ieni, Giovanni Tuccari, Caterina Ledda, Venerando Rapisarda
International Journal of Molecular Sciences.2018; 19(3): 685. CrossRef
Mechanisms of Aquaporin-Facilitated Cancer Invasion and Metastasis
Michael L. De Ieso, Andrea J. Yool
Frontiers in Chemistry.2018;[Epub] CrossRef
Aquaporin 1 suppresses apoptosis and affects prognosis in esophageal squamous cell carcinoma
Yuzo Yamazato, Atsushi Shiozaki, Daisuke Ichikawa, Toshiyuki Kosuga, Katsutoshi Shoda, Tomohiro Arita, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Mitsuo Kishimoto, Eiichi Konishi, Yoshinori Marunaka, Eigo Otsuji
Oncotarget.2018; 9(52): 29957. CrossRef
Aquaporin 1 expression is associated with response to adjuvant chemotherapy in stageï¿½II and III colorectal cancer
Hideko Imaizumi, Keiichiro Ishibashi, Seiichi Takenoshita, Hideyuki Ishida
Oncology Letters.2018;[Epub] CrossRef
Aquaporin 3 facilitates tumor growth in pancreatic cancer by modulating mTOR signaling
Xunwei Huang, Li Huang, Minhua Shao
Biochemical and Biophysical Research Communications.2017; 486(4): 1097. CrossRef
Prognostic implication of aquaporin 1 overexpression in resected lung adenocarcinoma†
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Interactive CardioVascular and Thoracic Surgery.2017; 25(6): 856. CrossRef

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