Journal of Pathology and Translational Medicine

Han Suk Ryu

6 Articles

The proteomic landscape shows oncologic relevance in cystitis glandularis: Jun Yong Kim, Dohyun Han, Hyeyoon Kim, Minsun Jung, Han Suk Ryu; J Pathol Transl Med. 2023;57(1):67-74. Published online December 22, 2022; DOI: https://doi.org/10.4132/jptm.2022.10.24

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Background
The relationship between cystitis glandularis (CG) and bladder malignancy remains unclear.
Methods
We identified the oncologic significance of CG at the molecular level using liquid chromatography-tandem mass spectrometry-based proteomic analysis of 10 CG, 12 urothelial carcinoma (UC), and nine normal urothelium (NU) specimens. Differentially expressed proteins (DEPs) were identified based on an analysis of variance false discovery rate < 0.05, and their functional enrichment was analyzed using a network model, Gene Set Enrichment Analysis, and Gene Ontology annotation.
Results
We identified 9,890 proteins across all samples and 1,139 DEPs among the three entities. A substantial number of DEPs overlapped in CG/NU, distinct from UC. Interestingly, we found that a subset of DEP clusters (n = 53, 5%) was differentially expressed in NU but similarly between CG and UC. This “UC-like signature” was enriched for reactive oxygen species (ROS) and energy metabolism, growth and DNA repair, transport, motility, epithelial-mesenchymal transition, and cell survival. Using the top 10 shortlisted DEPs, including SOD2, PRKCD, CYCS, and HCLS1, we identified functional elements related to ROS metabolism, development, and transport using network analysis. The abundance of these four molecules in UC/CG than in NU was consistent with the oncologic functions in CG.
Conclusions
Using a proteomic approach, we identified a predominantly non-neoplastic landscape of CG, which was closer to NU than to UC. We also confirmed a small subset of common DEPs in UC and CG, suggesting that altered ROS metabolism might imply potential cancerous risks in CG.

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Quantitative proteomics and immunohistochemistry uncover NT5DC2 as a diagnostic biomarker for papillary urothelial carcinoma
Jun Yong Kim, Jae Seok Lee, Dohyun Han, Ilias P. Nikas, Hyeyoon Kim, Minsun Jung, Han Suk Ryu
Heliyon.2024; 10(15): e35475. CrossRef
KRT18 as a Novel Biomarker of Urothelial Papilloma while Evaluating Low-Grade Papillary Urothelial Neoplasms: Bi-Center Analysis
Minsun Jung, Bohyun Kim, Jae Seok Lee, Jun Yong Kim, Dohyun Han, Kwangsoo Kim, Sunah Yang, Eun Na Kim, Hyeyooon Kim, Ilias P. Nikas, Sohyeon Yang, Kyung Chul Moon, Hyebin Lee, Han Suk Ryu
Pathobiology.2024; : 1. CrossRef

The application of high-throughput proteomics in cytopathology: Ilias P. Nikas, Han Suk Ryu; J Pathol Transl Med. 2022;56(6):309-318. Published online November 9, 2022; DOI: https://doi.org/10.4132/jptm.2022.08.30

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Abstract PDF

High-throughput genomics and transcriptomics are often applied in routine pathology practice to facilitate cancer diagnosis, assess prognosis, and predict response to therapy. However, the proteins rather than nucleic acids are the functional molecules defining the cellular phenotype in health and disease, whereas genomic profiling cannot evaluate processes such as the RNA splicing or posttranslational modifications and gene expression does not necessarily correlate with protein expression. Proteomic applications have recently advanced, overcoming the issue of low depth, inconsistency, and suboptimal accuracy, also enabling the use of minimal patient-derived specimens. This review aims to present the recent evidence regarding the use of high-throughput proteomics in both exfoliative and fine-needle aspiration cytology. Most studies used mass spectrometry, as this is associated with high depth, sensitivity, and specificity, and aimed to complement the traditional cytomorphologic diagnosis, in addition to identify novel cancer biomarkers. Examples of diagnostic dilemmas subjected to proteomic analysis included the evaluation of indeterminate thyroid nodules or prediction of lymph node metastasis from thyroid cancer, also the differentiation between benign and malignant serous effusions, pancreatic cancer from autoimmune pancreatitis, non-neoplastic from malignant biliary strictures, and benign from malignant salivary gland tumors. A few cancer biomarkers—related to diverse cancers involving the breast, thyroid, bladder, lung, serous cavities, salivary glands, and bone marrow—were also discovered. Notably, residual liquid-based cytology samples were suitable for satisfactory and reproducible proteomic analysis. Proteomics could become another routine pathology platform in the near future, potentially by using validated multi-omics protocols.

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Identification of NIFTP-Specific mRNA Markers for Reliable Molecular Diagnosis of Thyroid Tumors
So-Yeon Lee, Jong-Lyul Park, Kwangsoon Kim, Ja Seong Bae, Jae-Yoon Kim, Seon-Young Kim, Chan Kwon Jung
Endocrine Pathology.2023; 34(3): 311. CrossRef

Diagnostic distribution and pitfalls of glandular abnormalities in cervical cytology: a 25-year single-center study: Jung-A Sung, Ilias P. Nikas, Haeryoung Kim, Han Suk Ryu, Cheol Lee; J Pathol Transl Med. 2022;56(6):354-360. Published online November 9, 2022; DOI: https://doi.org/10.4132/jptm.2022.09.05

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Abstract PDF

Background
Detection of glandular abnormalities in Papanicolaou (Pap) tests is challenging. This study aimed to review our institute’s experience interpreting such abnormalities, assess cytohistologic concordance, and identify cytomorphologic features associated with malignancy in follow-up histology.
Methods
Patients with cytologically-detected glandular lesions identified in our pathology records from 1995 to 2020 were included in this study.
Results
Of the 683,197 Pap tests performed, 985 (0.144%) exhibited glandular abnormalities, 657 of which had tissue follow-up available. One hundred eighty-eight cases were cytologically interpreted as adenocarcinoma and histologically diagnosed as malignant tumors of various origins. There were 213 cases reported as atypical glandular cells (AGC) and nine cases as adenocarcinoma in cytology, yet they were found to be benign in follow-up histology. In addition, 48 cases diagnosed with AGC and six with adenocarcinoma cytology were found to have cervical squamous lesions in follow-up histology, including four squamous cell carcinomas. Among the cytomorphological features examined, nuclear membrane irregularity, three-dimensional clusters, single-cell pattern, and presence of mitoses were associated with malignant histology in follow-up.
Conclusions
This study showed our institute’s experience detecting glandular abnormalities in cervical cytology over a 25-year period, revealing the difficulty of this task. Nonetheless, the present study indicates that several cytological findings such as membrane irregularity, three-dimensional clusters, single-cell pattern, and evidence of proliferation could help distinguishing malignancy from a benign lesion.

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Analysis of atypical glandular cells in ThinPrep Pap smear and follow-up histopathology
Tengfei Wang, Yinan Hua, Lina Liu, Bing Leng
Baylor University Medical Center Proceedings.2024; 37(3): 403. CrossRef

High Cytoplasmic CXCR4 Expression Predicts Prolonged Survival in Triple-Negative Breast Cancer Patients Treated with Adjuvant Chemotherapy: Bobae Shim, Min‐Sun Jin, Ji Hye Moon, In Ae Park, Han Suk Ryu; J Pathol Transl Med. 2018;52(6):369-377. Published online October 1, 2018; DOI: https://doi.org/10.4132/jptm.2018.09.19

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Abstract PDF

Background
Chemokine receptor CXC chemokine receptor type 4 (CXCR4) and its ligand CXC motif chemokine 12 (CXCL12; stromal cell-derived factor-1) are implicated in tumor growth, metastasis, and tumor cell-microenvironment interaction. A number of studies have reported that increased CXCR4 expression is associated with worse prognosis in triple-negative breast cancer (TNBC), but its prognostic significance has not been studied in TNBC patients treated with adjuvant chemotherapy.
Methods
Two hundred eighty-three TNBC patients who received adjuvant chemotherapy were retrospectively analyzed. Tissue microarray was constructed from formalinfixed, paraffin-embedded tumor tissue and immunohistochemistry for CXCR4 and CXCL12 was performed. Expression of each marker was compared with clinicopathologic characteristics and outcome.
Results
High cytoplasmic CXCR4 expression was associated with younger age (p = .008), higher histologic grade (p = .007) and lower pathologic stage (p = .045), while high CXCL12 expression was related to larger tumor size (p = .045), positive lymph node metastasis (p = .005), and higher pathologic stage (p = .017). The patients with high cytoplasmic CXCR4 experienced lower distant recurrence (p = .006) and better recurrence-free survival (RFS) (log-rank p = .020) after adjuvant chemotherapy. Cytoplasmic CXCR4 expression remained an independent factor of distant recurrence (p = .019) and RFS (p = .038) after multivariate analysis.
Conclusions
High cytoplasmic CXCR4 expression was associated with lower distant recurrence and better RFS in TNBC patients treated with adjuvant chemotherapy. This is the first study to correlate high CXCR4 expression to better TNBC prognosis, and the underlying mechanism needs to be elucidated in further studies.

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Bisphenol A-induced cancer-associated adipocytes promotes breast carcinogenesis via CXCL12/AKT signaling
Zhiyuan Dong, Liping He, Jinyi Wu, Chunfeng Xie, Shanshan Geng, Jieshu Wu, Caiyun Zhong, Xiaoting Li
Molecular and Cellular Endocrinology.2025; 599: 112473. CrossRef
Distinct profiles of proliferating CD8+/TCF1+ T cells and CD163+/PD-L1+ macrophages predict risk of relapse differently among treatment-naïve breast cancer subtypes
Konstantinos Ntostoglou, Sofia D. P. Theodorou, Tanja Proctor, Ilias P. Nikas, Sinclair Awounvo, Athanasia Sepsa, Vassilis Georgoulias, Han Suk Ryu, Ioannis S. Pateras, Christos Kittas
Cancer Immunology, Immunotherapy.2024;[Epub] CrossRef
Unravelling the CXCL12/CXCR4 Axis in breast cancer: Insights into metastasis, microenvironment interactions, and therapeutic opportunities
Priyanka Garg, Venkateswara Rao Jallepalli, Sonali Verma
Human Gene.2024; 40: 201272. CrossRef
New Emerging Chemokine Receptors: CCR5 or CXCR5 on Tumor Is Associated with Poor Response to Chemotherapy and Poor Prognosis in Locally Advanced Triple-Negative Breast Cancer
Neslihan Cabioglu, Semen Onder, Hüseyin Karatay, Aysel Bayram, Gizem Oner, Mustafa Tukenmez, Mahmut Muslumanoglu, Abdullah Igci, Ahmet Dinccag, Vahit Ozmen, Adnan Aydiner, Pınar Saip, Ekrem Yavuz
Cancers.2024; 16(13): 2388. CrossRef
Cancer-Associated-Fibroblast-Mediated Paracrine and Autocrine SDF-1/CXCR4 Signaling Promotes Stemness and Aggressiveness of Colorectal Cancers
Chao-Yang Chen, Shih-Hsien Yang, Ping-Ying Chang, Su-Feng Chen, Shin Nieh, Wen-Yen Huang, Yu-Chun Lin, Oscar Kuang-Sheng Lee
Cells.2024; 13(16): 1334. CrossRef
Associations of CXCL12 polymorphisms with clinicopathological features in breast cancer: a case-control study
Shuai Lin, Yi Zheng, Meng Wang, Linghui Zhou, Yuyao Zhu, Yujiao Deng, Ying Wu, Dai Zhang, Na Li, Huafeng Kang, Zhijun Dai
Molecular Biology Reports.2022; 49(3): 2255. CrossRef
The clinicopathological and prognostic value of CXCR4 expression in patients with lung cancer: a meta-analysis
Liping Qiu, Yuanyuan Xu, Hui Xu, Biyun Yu
BMC Cancer.2022;[Epub] CrossRef
Demystifying the CXCR4 conundrum in cancer biology: Beyond the surface signaling paradigm
Mushtaq Ahmad Nengroo, Muqtada Ali Khan, Ayushi Verma, Dipak Datta
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2022; 1877(5): 188790. CrossRef
Targeted dendrimers for antagonizing the migration and viability of NALM-6 lymphoblastic leukemia cells
Chuda Chittasupho, Chaiyawat Aonsri, Witcha Imaram
Bioorganic Chemistry.2021; 107: 104601. CrossRef
CXCR4 and RANK Combination as a Predictor of Breast Cancer Bone Metastasis in Indonesia
Yulian Erwin D
Journal of Surgery and Surgical Research.2021; : 020. CrossRef
CXCL12/CXCR4 axis in the microenvironment of solid tumors: A critical mediator of metastasis
Keywan Mortezaee
Life Sciences.2020; 249: 117534. CrossRef
Impact of the Chemokine Receptors CXCR4 and CXCR7 on Clinical Outcome in Adrenocortical Carcinoma
Irina Chifu, Britta Heinze, Carmina T. Fuss, Katharina Lang, Matthias Kroiss, Stefan Kircher, Cristina L. Ronchi, Barbara Altieri, Andreas Schirbel, Martin Fassnacht, Stefanie Hahner
Frontiers in Endocrinology.2020;[Epub] CrossRef

Cytologic Diagnosis of Metastatic Alveolar Rhabdomyosarcoma in Cerebrospinal Fluid: A Case Report: Bobae Shim, Jiwon Koh, Ji Hye Moon, In Ae Park, Han Suk Ryu; J Pathol Transl Med. 2018;52(4):262-266. Published online June 14, 2018; DOI: https://doi.org/10.4132/jptm.2018.05.15

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Abstract PDF

Rhabdomyosarcoma is a malignant soft tissue tumor which shows skeletal muscle differentiation. Leptomeningeal metastasis can occur as a late complication, but currently there are no reports that have documented the cytologic features in cerebrospinal fluid (CSF). We report a case of metastatic alveolar rhabdomyosarcoma diagnosed in the CSF of a 28-year-old male who was originally diagnosed with rhabdomyosarcoma on the neck, and that went through systemic therapy. The tumor was positive for anaplastic lymphoma kinase, but progressed despite additional therapy with crizotinib. The CSF specimen revealed small round cells, large atypical cells with abundant cytoplasm and eccentric nuclei, and cells with horseshoe-shaped nuclei. These cytologic findings were in agreement with previous literature and well-correlated with histopathology. This is the first report to document the cytologic feature of rhabdomyosarcoma in CSF. In many cases it is difficult to perform ancillary tests in a CSF specimen and cytopathologists should be aware of the cytomorphologic characteristics to avoid misdiagnosis.

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A Review of Effusion Cytomorphology of Small Round Cell Tumors
Lucy M. Han, Christopher J. VandenBussche, Mads Abildtrup, Ashish Chandra, Poonam Vohra
Acta Cytologica.2022; 66(4): 336. CrossRef
Cytologic diagnosis of metastatic embryonal rhabdomyosarcoma in cerebrospinal fluid: A case report
Muxia Yan, Ying Wu, Jianqing Xia, Xiaohong Zhang, Yiqian Wang
Diagnostic Cytopathology.2021;[Epub] CrossRef
Effusion cytology of epithelioid rhabdomyosarcoma
Andrew A. Renshaw, Edwin W. Gould
Diagnostic Cytopathology.2019; 47(10): 1042. CrossRef

Primary Monophasic Synovial Sarcoma Arising in the Mesentery: Case Report of an Extremely Rare Mesenteric Sarcoma Confirmed by Molecular Detection of a SYT-SSX2 Fusion Transcript: Han Suk Ryu, Ilyeong Heo, Jae Soo Koh, Sung-Ho Jin, Hye Jin Kang, Soo Youn Cho; Korean J Pathol. 2012;46(2):187-191. Published online April 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.187

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Abstract PDF

Synovial sarcoma arises in the para-articular tissues, and it can also occur in various unexpected sites. We report a rare case of primary monophasic synovial sarcoma (MSS) arising in the mesentery. A 59-year-old man presented with a palpable abdominal mass. On microscopic examination, the entire tumor comprised a dense proliferation of the spindle cells without epithelial components. The tumor cells were positive for transducin-like enhancer of split 1, bcl-2, epithelial membrane antigen and CD99 but negative for CD34, CD117, alpha-smooth muscle actin, cytokeratin, and calretinin on immunohistochemistry. The reverse transcriptase-polymerase chain reaction revealed a single 151-bp fragment representing the SYT-SSX2 fusion transcript. Because mesenteric MSS is extremely rare and many cases display histologic findings that overlap with those of more frequently involved tumors such as hemangiopericytoma and gastrointestinal stromal tumor, there is a chance of making an incorrect diagnosis that can result in an inappropriate treatment.

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A case of primary mesenteric synovial sarcoma: a challenging presentation
Nihed Abdessayed, Malek Barka, Samiha Mabrouk, Zeineb Nfikha, Zeineb Maatoug, Yosra Fejji, Mohamed Salah Jarrar, Sabri Youssef, Moncef Mokni
Surgical Case Reports.2023;[Epub] CrossRef
Giant solitary fibrous tumor of the pelvis: A case report and review of literature
Gerardo Palmieri, Carmine Grassi, Luigi Conti, Filippo Banchini, Maria Diletta Daccò, Gaetano M. Cattaneo, Patrizio Capelli
International Journal of Surgery Case Reports.2020; 77: S52. CrossRef
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Annales de Pathologie.2015; 35(6): 506. CrossRef

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