Journal of Pathology and Translational Medicine

Original Article

International Academy of Cytology standardized reporting of breast fine-needle aspiration cytology with cyto-histopathological correlation of breast carcinoma: Shweta Pai; J Pathol Transl Med. 2024;58(5):241-248. Published online September 13, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.14

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Abstract PDF: Background
The International Academy of Cytology (IAC) has developed a standardized approach for reporting the findings of breast fine-needle aspiration cytology (FNAC). Accordingly, there are five chief categories of breast lesions, C1 (insufficient material), C2 (benign), C3 (atypical), C4 (suspicious), and C5 (malignant). The prognostication and management of breast carcinoma can be performed readily on the basis of this classification system. The aim of this study was to classify various breast lesions into one of the above-named categories and to further grade the C5 lesions specifically using the Robinson system. The latter grades were then correlated with modified Scarff-Bloom-Richardson (SBR) grades.
Methods
This retrospective study was undertaken in the pathology department of a hospital located in the urban part of the city of Bangalore. All FNAC procedures performed on breast lumps spanning the year 2020 were included in the study.
Results
A total of 205 breast lesions was classified according to the IAC guidelines into C1 (6 cases, 2.9%), C2 (151 cases, 73.7%), C3 (13 cases, 6.3%), C4 (5 cases, 2.5%), and C5 (30 cases, 14.6%) groups. The C5 cases were further graded using Robinson’s system. The latter showed a significant correlation with the SBR system (concordance=83.3%, Spearman correlation=0.746, Kendall’s tau-b=0.736, kappa=0.661, standard error=0.095, p≤.001).
Conclusions
A standardized approach for FNAC reporting of breast lesions, as advocated for by the IAC, improves the quality and clarity of the reports and assures diagnostic reproducibility on a global scale. Further, the cytological grading of C5 lesions provides reliable cyto-prognostic scores that can help assess a tumor’s aggressiveness and predict its histological grade.

Review

Perspectives on single-nucleus RNA sequencing in different cell types and tissues: Nayoung Kim, Huiram Kang, Areum Jo, Seung-Ah Yoo, Hae-Ock Lee; J Pathol Transl Med. 2023;57(1):52-59. Published online January 10, 2023; DOI: https://doi.org/10.4132/jptm.2022.12.19

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Single-cell RNA sequencing has become a powerful and essential tool for delineating cellular diversity in normal tissues and alterations in disease states. For certain cell types and conditions, there are difficulties in isolating intact cells for transcriptome profiling due to their fragility, large size, tight interconnections, and other factors. Single-nucleus RNA sequencing (snRNA-seq) is an alternative or complementary approach for cells that are difficult to isolate. In this review, we will provide an overview of the experimental and analysis steps of snRNA-seq to understand the methods and characteristics of general and tissue-specific snRNA-seq data. Knowing the advantages and limitations of snRNA-seq will increase its use and improve the biological interpretation of the data generated using this technique.

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Original Articles

Expression of specific microRNAs in tissue and plasma in colorectal cancer: Allan Fellizar, Vivencio Refuerzo, John Donnie Ramos, Pia Marie Albano; J Pathol Transl Med. 2023;57(3):147-157. Published online May 3, 2022; DOI: https://doi.org/10.4132/jptm.2022.02.19

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Abstract PDF

Background
MicroRNAs (miRNA/miR) play significant roles in the regulation of cell differentiation, cell cycle progression, and apoptosis. They become dysregulated during carcinogenesis and are eventually released into the circulation, enabling their detection in body fluids. Thus, this study compared the miRNA expression in tissue and plasma samples of colorectal cancer (CRC) patients and clinically healthy controls and determined miRNA expression as a potential CRC biomarker.
Methods
Using quantitative reverse transcription polymerase chain reaction (RT-qPCR), miR-21-5p, miR-29a-3p, miR-92a-3p, miR-135b-5p, miR-196b-5p, and miR-197-3p, expression was analyzed and compared between the malignant (n = 41) and the adjacent neoplasm free mucosal tissues (n = 41) of CRC patients. The findings were validated in plasma samples (n = 36) collected from the same CRC patients prior to surgery or any form of treatment and compared to plasma from their age and sex-matched controls (n = 36).
Results
MiR-21-5p, miR-29a-3p, miR-92a-3p, and miR- 196b-5p were upregulated and miR-135b-5p was downregulated in CRC malignant tissues compared to their expression in adjacent neoplasm-free tissue. This was further observed in the plasma of the same CRC cases compared to controls. MiR-92a-3p showed itself the most sensitive (0.93; p < .001) and most specific (0.95; p < .001) in detecting CRC in tissue. In plasma, miR-196b-5p was the most sensitive (0.97; p < .001) and specific (0.94; p < .001) in detecting CRC. Plasma miR-92a-3p and miR-196b-5p were the most sensitive (0.95; p < .001) and specific (0.94; p < .001) in the early detection of CRC.
Conclusions
Results show that specific miRNAs dysregulated in malignant tissues are released and can be detected in the circulation, supporting their potential as non-invasive biomarkers of CRC.

Citations

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Except for Robust Outliers, Rapamycin Increases Lesion Burden in a Murine Model of Cerebral Cavernous Malformations
Roberto J. Alcazar-Felix, Robert Shenkar, Christian R. Benavides, Akash Bindal, Abhinav Srinath, Ying Li, Serena Kinkade, Tatiana Terranova, Evon DeBose-Scarlett, Rhonda Lightle, Dorothy DeBiasse, Hanadi Almazroue, Diana Vera Cruz, Sharbel Romanos, Aditya
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Identification of miRNAs Present in Cell- and Plasma-Derived Extracellular Vesicles—Possible Biomarkers of Colorectal Cancer
Marzena Lenart, Izabela Siemińska, Rafał Szatanek, Anna Mordel, Antoni Szczepanik, Mateusz Rubinkiewicz, Maciej Siedlar, Monika Baj-Krzyworzeka
Cancers.2024; 16(13): 2464. CrossRef
The Role of Extracellular Vesicles in Colorectal Cancer
Yujian Xia, Chaoran Yu, Ernest Johann Helwig, Yousheng Li
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HNRNPA2B1-Mediated MicroRNA-92a Upregulation and Section Acts as a Promising Noninvasive Diagnostic Biomarker in Colorectal Cancer
Yiling Li, Kexin Li, Xiaoying Lou, Yue Wu, Samuel Seery, Danfei Xu, Yuqing Pei, Benheng Qian, Yuxin Wu, Shuang Liang, Kui Wu, Wei Cui
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Role of salivary miRNAs in the diagnosis of gastrointestinal disorders: a mini-review of available evidence
Maria Oana Săsăran, Claudia Bănescu
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Chau-Ming Kan, Xiao Meng Pei, Martin Ho Yin Yeung, Nana Jin, Simon Siu Man Ng, Hin Fung Tsang, William Chi Shing Cho, Aldrin Kay-Yuen Yim, Allen Chi-Shing Yu, Sze Chuen Cesar Wong
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Serena Ascrizzi, Grazia Maria Arillotta, Katia Grillone, Giulio Caridà, Stefania Signorelli, Asad Ali, Caterina Romeo, Pierfrancesco Tassone, Pierosandro Tagliaferri
Cancers.2023; 15(15): 3930. CrossRef

Upward trend in follicular lymphoma among the Korean population: 10-year experience at a large tertiary institution: Meejeong Kim, Hee Sang Hwang, Hyungwoo Cho, Dok Hyun Yoon, Cheolwon Suh, Chan Sik Park, Heounjeong Go, Jooryung Huh; J Pathol Transl Med. 2021;55(5):330-337. Published online September 2, 2021; DOI: https://doi.org/10.4132/jptm.2021.07.25

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Abstract PDF Supplementary Material

Background
Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) in Western countries. However, it is relatively rare in Asia. This study examined epidemiologic characteristics of FL in South Korea, with an emphasis on recent trends of increase in cases.
Methods
We retrospectively examined 239 cases of newly diagnosed FL at a large tertiary institution in Korea (Asan Medical Center, Seoul, Republic of Korea) between 2008 and 2017. Age-adjusted incidence rates and clinicopathological variables were analyzed, and joinpoint regression analysis was used to identify the changes.
Results
The age-adjusted incidence of FL significantly increased during the study period (p = .034), and the ratio of (relative incidence) patients with FL to patients with NHL increased from 4.28% to 9.35% in the same period. Over the 10-year study assessment duration, the proportion of patients with stage III/IV FL (p = .035) and expression of BCL2 (p = .022) or BCL6 (p = .039) significantly increased. From 2013–2017, the proportion of patients with highrisk Follicular Lymphoma International Prognostic Index (FLIPI) score increased (21.5% to 28.7%), whereas that of low-risk FLIPI decreased (55.4% to 38.6%), although those results were not statistically significant (p = .066).
Conclusions
We found an increasing incidence of FL, with a disproportionate increase in the incidence of high-stage disease and recent changes in the clinicopathologic features of the Korean patient population.

Citations

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Incidence Trend of Follicular Lymphoma in Taiwan Compared to Japan and Korea, 2001–2019
Liang-Chun Chiu, Chih-Wen Lin, Hung-Ju Li, Jian-Han Chen, Fu-Cheng Chuang, Sheng-Fung Lin, Yu Chang, Yu-Chieh Su
Journal of Clinical Medicine.2023; 12(4): 1417. CrossRef
A Case Report on the Complete Response of a Patient with Recurrent Follicular Lymphoma Treated with Integrative Medicine
Kyung-dug Park, Jisoo Kim, Yoona Oh, Beom-Jin Jeong, Yu-jin Jung, Sunhwi Bang
The Journal of Internal Korean Medicine.2023; 44(3): 585. CrossRef
Recent Updates on Diagnosis and Treatment of Follicular Lymphoma
Ga-Young Song, Deok-Hwan Yang
The Korean Journal of Medicine.2023; 98(5): 231. CrossRef
Classical Hodgkin lymphoma following follicular lymphoma: a case report
Bomi Kim
Journal of Yeungnam Medical Science.2023; 40(Suppl): S113. CrossRef
Incidence, clinicopathological features and genetics of in‐situ follicular neoplasia: a comprehensive screening study in a Japanese cohort
Naoki Oishi, Takahiro Segawa, Kunio Miyake, Kunio Mochizuki, Tetsuo Kondo
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Automated immunohistochemical assessment ability to evaluate estrogen and progesterone receptor status compared with quantitative reverse transcription-polymerase chain reaction in breast carcinoma patients: Taesung Jeon, Aeree Kim, Chungyeul Kim; J Pathol Transl Med. 2021;55(1):33-42. Published online December 3, 2020; DOI: https://doi.org/10.4132/jptm.2020.09.29

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Abstract PDF

Background
This study aimed to investigate the capability of an automated immunohistochemical (IHC) evaluation of hormonal receptor status in breast cancer patients compared to a well-validated quantitative reverse transcription–polymerase chain reaction (RT-qPCR) method.
Methods
This study included 93 invasive breast carcinoma cases that had both standard IHC assay and Oncotype Dx assay results. The same paraffin blocks on which Oncotype Dx assay had been performed were selected. Estrogen receptor (ER) and progesterone receptor (PR) receptor status were evaluated through IHC stains using SP1 monoclonal antibody for ER, and 1E2 monoclonal antibody for PR. All ER and PR immunostained slides were scanned, and invasive tumor areas were marked. Using the QuantCenter image analyzer provided by 3DHISTECH, IHC staining of hormone receptors was measured and converted to histochemical scores (H scores). Pearson correlation coefficients were calculated between Oncotype Dx hormone receptor scores and H scores, and between Oncotype Dx scores and Allred scores.
Results
H scores measured by an automated imaging system showed high concordance with RT-qPCR scores. ER concordance was 98.9% (92/93), and PR concordance was 91.4% (85/93). The correlation magnitude between automated H scores and RT-qPCR scores was high and comparable to those of Allred scores (for ER, 0.51 vs. 0.37 [p=.121], for PR, 0.70 vs. 0.72 [p=.39]).
Conclusions
Automated H scores showed a high concordance with quantitative mRNA expression levels measured by RT-qPCR.

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Vision Transformers for Breast Cancer Human Epidermal Growth Factor Receptor 2 Expression Staging without Immunohistochemical Staining
Gelan Ayana, Eonjin Lee, Se-woon Choe
The American Journal of Pathology.2024; 194(3): 402. CrossRef
Extrahepatic Bile Duct Organoids as a Model to Study Ischemia/Reperfusion Injury During Liver Transplantation
P. Kreiner, E. Eggenhofer, L. Schneider, C. Rejas, M. Goetz, N. Bogovic, S. M. Brunner, K. Evert, H. J. Schlitt, E. K. Geissler, H. Junger
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Marker assessments inER‐positive breast cancers: old markers, new applications?
Joshua J X Li, Gary M Tse
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Rohit Bhargava, David J. Dabbs
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Dose-Dependent Relationship between Protection of Thioacetamide-Induced Acute Liver Injury and Hyperammonemia and Concentration of Lactobacillus salivarius Li01 in Mice
Pengcheng Lou, Yangfan Shen, Aoxiang Zhuge, Longxian Lv, Xueling Zhu, Yin Yuan, Liya Yang, Kaicen Wang, Bo Li, Lanjuan Li, Joanna B. Goldberg
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Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system, compared to p16 immunohistochemistry and HPV RNA in-situ hybridization: Hezhen Ren, Jennifer Pors, Christine Chow, Monica Ta, Simona Stolnicu, Robert Soslow, David Huntsman, Lynn Hoang; J Pathol Transl Med. 2020;54(6):480-488. Published online August 31, 2020; DOI: https://doi.org/10.4132/jptm.2020.07.18

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Abstract PDF

Background
The International Endocervical Adenocarcinoma Criteria and Classification (IECC) separated endocervical adenocarcinomas into human papillomavirus (HPV) associated (HPVA) and non–HPV-associated (NHPVA) categories by morphology alone. Our primary objective was to assess the accuracy of HPV prediction by the IECC system compared to p16 immunohistochemistry and HPV RNA in-situ hybridization (RISH). Our secondary goal was to directly compare p16 and HPV RISH concordance.
Methods
Cases were classified by IECC and stained for p16 and HPV RISH on tissue microarray, with discordant p16/HPV RISH cases re-stained on whole tissue sections. Remaining discordant cases (p16/HPV, IECC/p16, IECC/HPV discordances) were re-reviewed by the original pathologists (n = 3) and external expert pathologists (n = 2) blinded to the p16 and HPV RISH results. Final IECC diagnosis was assigned upon independent agreement between all reviewers.
Results
One hundred and eleven endocervical adenocarcinomas were classified originally into 94 HPVA and 17 NHPVA cases. p16 and HPV RISH was concordant in 108/111 cases (97%) independent of the IECC. HPV RISH and p16 was concordant with IECC in 103/111 (93%) and 106/111 (95%), respectively. After expert review, concordance improved to 107/111 (96%) for HPV RISH. After review of the eight discordant cases, one remained as HPVA, four were reclassified to NHPVA from HPVA, two were unclassifiable, and one possibly represented a mixed usual and gastric-type adenocarcinoma.
Conclusions
p16 and HPV RISH have excellent concordance in endocervical adenocarcinomas, and IECC can predict HPV status in most cases. Focal apical mitoses and apoptotic debris on original review led to the misclassification of several NHPVA as HPVA.

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Joint detection of multiple HPV-testing technologies and evaluation of clinicopathological characteristics discriminate between HPV-independent and low-copy HPV-associated cervical squamous cell carcinoma (CSCC) -an analysis of 3869 cases
Linghui Lu, Tianqi Liu, Shunni Wang, Jing Li, Feiran Zhang, Yan Ning, Yiqin Wang
Gynecologic Oncology.2023; 170: 59. CrossRef
Incidence and Clinicopathologic Characteristics of Human Papillomavirus–independent Invasive Squamous Cell Carcinomas of the Cervix
Simona Stolnicu, Douglas Allison, Aaron M. Praiss, Basile Tessier-Cloutier, Amir Momeni Boroujeni, Jessica Flynn, Alexia Iasonos, Rene Serrette, Lien Hoang, Andrei Patrichi, Cristina Terinte, Anna Pesci, Claudia Mateoiu, Ricardo R. Lastra, Takako Kiyokawa
American Journal of Surgical Pathology.2023; 47(12): 1376. CrossRef
Testing Algorithms for the Diagnosis of Malignant Glandular Tumors of the Uterine Cervix Histotyped per the International Endocervical Adenocarcinoma Criteria and Classification (IECC) System
Máire A. Duggan, Qiuli Duan, Ruth M. Pfeiffer, Mary Anne Brett, Sandra Lee, Mustapha Abubakar, Martin Köbel, Monica Rodriguez, Aylin Sar
Applied Immunohistochemistry & Molecular Morphology.2022; 30(2): 91. CrossRef
Local and Metastatic Relapses in a Young Woman with Papillary Squamous Cell Carcinoma of the Uterine Cervix
Ha Young Woo, Hyun-Soo Kim
Diagnostics.2022; 12(3): 599. CrossRef
Clinical correlation of lymphovascular invasion and Silva pattern of invasion in early-stage endocervical adenocarcinoma: proposed binary Silva classification system
Simona Stolnicu, Lien Hoang, Noorah Almadani, Louise De Brot, Glauco Baiocchi, Graziele Bovolim, Maria Jose Brito, Georgia Karpathiou, Antonio Ieni, Esther Guerra, Takako Kiyokawa, Pavel Dundr, Carlos Parra-Herran, Sofia Lérias, Ana Felix, Andres Roma, An
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Reproducibility of Morphologic Parameters of the International Endocervical Adenocarcinoma Criteria and Classification System and Correlation With Clinicopathologic Parameters: A Multi-Institutional Study
Pinar Bulutay, Nihan Haberal, Özlem Özen, Özlem Erdem, Emine H. Zeren, İbrahim Kulac, Çagatay Taskiran, Dogan Vatansever, Ali Ayhan, Nilgün Kapucuoğlu
International Journal of Gynecological Pathology.2022; 41(5): 447. CrossRef
HPV-Negative Cervical Cancer: A Narrative Review
Francesca Arezzo, Gennaro Cormio, Vera Loizzi, Gerardo Cazzato, Viviana Cataldo, Claudio Lombardi, Giuseppe Ingravallo, Leonardo Resta, Ettore Cicinelli
Diagnostics.2021; 11(6): 952. CrossRef
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Hezhen Ren, Noorah Almadani, Jennifer Pors, Samuel Leung, Julie Ho, Christine Chow, Monica Ta, Kay J. Park, Simona Stolnicu, Robert Soslow, David Huntsman, Blake C. Gilks, Lynn Hoang
International Journal of Gynecological Pathology.2021; 40(6): 533. CrossRef

Case Study

Primary carcinoid tumor in the external auditory canal: Dong Hae Chung, Gyu Cheol Han, Na Rae Kim; J Pathol Transl Med. 2020;54(2):184-187. Published online November 13, 2019; DOI: https://doi.org/10.4132/jptm.2019.11.07

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Abstract PDF

A 39-year-old man visited the department of otolaryngology due to an ongoing hearing disturbance that had lasted for 1 year. Temporal bone computed tomography revealed soft tissue density nearly obliterating the left external auditory canal (EAC). The mass was composed of sheets of round tumor cells containing moderate amounts of fine granular cytoplasm and salt and pepper chromatin. Neither mitosis nor necrosis was found. The Ki-67 proliferation index was less than 2%. Cells were positive for CD56 and synaptophysin but negative for chromogranin, cytokeratin (CK) 20, and CK7. Based on these findings, the tumor was diagnosed as a carcinoid tumor, well differentiated neuroendocrine carcinoma, grade 1 (G1) according to current World Health Organization (WHO) classification of head and neck tumors; and a neuroendocrine tumor, G1 according to neuroendocrine neoplasm (NEN)-2018 WHO standard classification. He remained free of local recurrence and metastasis after 20 months of follow up. To date, only six cases of primary NENs in the EAC have been reported. Metastatic tumor should be included in the differential diagnoses. Because of its rarity, the prognosis and treatment have not yet been clarified.

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Incidental finding of a neuroendocrine neoplasm in a suspected ear canal exostosis
Alexander Wieck Fjaeldstad, Gerda Elisabeth Villadsen, Gitte Dam, Stephen Jacques Hamilton-Dutoit, Thomas Winther Frederiksen
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Original Articles

MicroRNA-374a Expression as a Prognostic Biomarker in Lung Adenocarcinoma: Yeseul Kim, Jongmin Sim, Hyunsung Kim, Seong Sik Bang, Seungyun Jee, Sungeon Park, Kiseok Jang; J Pathol Transl Med. 2019;53(6):354-360. Published online October 24, 2019; DOI: https://doi.org/10.4132/jptm.2019.10.01

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Abstract PDF

Background
Lung cancer is the most common cause of cancer-related death, and adenocarcinoma is the most common histologic subtype. MicroRNA is a small non-coding RNA that inhibits multiple target gene expression at the post-transcriptional level and is commonly dysregulated in malignant tumors. The purpose of this study was to analyze the expression of microRNA-374a (miR-374a) in lung adenocarcinoma and correlate its expression with various clinicopathological characteristics.
Methods
The expression level of miR-374a was measured in 111 formalin-fixed paraffin-embedded lung adenocarcinoma tissues using reverse transcription-quantitative polymerase chain reaction assays. The correlation between miR-374a expression and clinicopathological parameters, including clinical outcome, was further analyzed.
Results
High miR-374 expression was correlated with advanced pT category (chi-square test, p=.004) and pleural invasion (chi-square test, p=.034). Survival analysis revealed that patients with high miR-374a expression had significantly shorter disease-free survival relative to those with low miR-374a expression (log-rank test, p=.032).
Conclusions
miR-374a expression may serve as a potential prognostic biomarker for predicting recurrence in early stage lung adenocarcinoma after curative surgery.

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Upregulated miR-374a-5p drives psoriasis pathogenesis through WIF1 downregulation and Wnt5a/NF-κB activation
Jing Ma, Lu Gan, Hongying Chen, Lihao Chen, Yu Hu, Chao Luan, Kun Chen, Jiaan Zhang
Cellular Signalling.2024; 119: 111171. CrossRef
Cell-free plasma miRNAs analysis for low invasive lung cancer diagnostics
M. Yu. Konoshenko, P. P. Laktionov, Yu. A. Lancuhaj, S. V. Pak, S. E. Krasilnikov, O. E. Bryzgunova
Advances in Molecular Oncology.2023; 10(2): 78. CrossRef
MicroRNA‑mediated regulation in lung adenocarcinoma: Signaling pathways and potential therapeutic implications (Review)
Jiye Liu, Fei Zhang, Jiahe Wang, Yibing Wang
Oncology Reports.2023;[Epub] CrossRef
Dysregulation of miR-374a is involved in the progression of diabetic retinopathy and regulates the proliferation and migration of retinal microvascular endothelial cells
Zhanhong Wang, Xiao Zhang, Yanjun Wang, Dailing Xiao
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Differential MicroRNA Expression between EGFR T790M and L858R Mutated Lung Cancer: Ji Yeon Kim, Woo Jeong Lee, Ha Young Park, Ahrong Kim, Dong Hoon Shin, Chang Hun Lee; J Pathol Transl Med. 2018;52(5):275-282. Published online August 16, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.29

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Abstract PDF Supplementary Material

Background
MicroRNAs (miRNAs) are short, non-coding RNAs that mediate post-transcriptional gene regulation. They are commonly deregulated in human malignancies, including non-small cell lung cancer (NSCLC). The aim of this study is to investigate miRNA expression in T790M-mutated NSCLC resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors.
Methods
Six cases of resected NSCLC harboring the T790M mutation were examined. We performed miRNA time polymerase chain reaction (PCR) array profiling using EGFR T790M-mutated NSCLC and L858R-mutated NSCLC. Once identified, miRNAs that were differentially expressed between the two groups were validated by quantitative real-time polymerase chain reaction (qRT-PCR).
Results
miRNA PCR array profiling revealed three up-regulated miRNAs whose expression levels were altered 4.0-fold or more in the EGFR T790M mutation group than in the L858R group: miR-1 (fold change, 4.384), miR-196a (fold change, 4.138), and miR-124 (fold change, 4.132). The three differentially expressed miRNAs were validated by qRT-PCR, and they were found to be overexpressed in the T790M group relative to L858R group. In particular, expression levels of miR-1 and miR-124 were significantly higher in the T790M group (p-value of miR-1 = .004, miR-124 = .007, miR-196a = .096).
Conclusions
MiR-1, miR-124, and miR-196a are overexpressed in EGFR T790M mutated NSCLC.

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Whole exome sequencing and MicroRNA profiling of lung adenocarcinoma identified risk prediction features for tumors at stage I and its substages
Hao Ho, Sung-Liang Yu, Hsuan-Yu Chen, Shin-Sheng Yuan, Kang-Yi Su, Yi-Chiung Hsu, Chung-Ping Hsu, Cheng-Yen Chuang, Ya-Hsuan Chang, Yu-Cheng Li, Chiou-Ling Cheng, Gee-Chen Chang, Pan-Chyr Yang, Ker-Chau Li
Lung Cancer.2023; 184: 107352. CrossRef
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Review

Extracellular Vesicles and the Promise of Continuous Liquid Biopsies: Don Armstrong, Derek E. Wildman; J Pathol Transl Med. 2018;52(1):1-8. Published online January 15, 2018; DOI: https://doi.org/10.4132/jptm.2017.05.21

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Abstract PDF

The rapid and accurate diagnosis of patients with minimally invasive procedures was once only found in science fiction. However, the discovery of extracellular vesicles (EVs) and their near ubiquity in body fluids, coupled with the advent of inexpensive next generation sequencing techniques and EV purification protocols, promises to make science fiction a reality. Purifying and sequencing the RNA content of EV from routine blood draws and urine samples are likely to enable pathologists and physicians to diagnose and track the progress of diseases in many inaccessible tissues in the near future. Here we present the evolutionary background of EV, summarize the biology of EV formation and cargo selection, and discuss the current barriers to making continuous liquid biopsies through the use of EV a science reality.

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Original Article

Long Non-coding RNA HOTAIR Expression in Diffuse Large B-Cell Lymphoma: In Relation to Polycomb Repressive Complex Pathway Proteins and H3K27 Trimethylation: Eun Ji Oh, Soo Hee Kim, Woo Ick Yang, Young Hyeh Ko, Sun Och Yoon; J Pathol Transl Med. 2016;50(5):369-376. Published online August 22, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.06

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Abstract PDF

Background
A long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) is involved in epigenetic regulation through chromatin remodeling by recruiting polycomb repressive complex 2 (PRC2) proteins (EZH2, SUZ12, and EED) that induce histone H3 trimethylation at lysine 27 (H3K27me3). Deregulation of c-MYC and interaction between c-MYC and EZH2 are well known in lymphomagenesis; however, little is known about the expression status of HOTAIR in diffuse large B-cell lymphomas (DLBCLs).
Methods
The expression status of PRC2 (EZH2, SUZ12, and EED), H3K27me3, c-MYC, and BCL2 was analyzed using immunohistochemistry (n = 231), and HOTAIR was investigated by a quantification real-time polymerase chain reaction method (n = 164) in DLBCLs.
Results
The present study confirmed the positive correlation among PRC2 proteins, H3K27me3, and c-MYC in DLBCLs. Expression level of HOTAIR was also positively correlated to EZH2 (p < .05, respectively). Between c-MYC and HOTAIR, and between c- MYC/BCL2 co-expression and HOTAIR, however, negative correlation was observed in DLBCLs (p < .05, respectively). High level of H3K27me3 was determined as an independent prognostic marker in poor overall survival (hazard ratio, 2.0; p = .023) of DLBCL patients. High expression of HOTAIR, however, was associated with favorable overall survival (p = .004) in the univariate analysis, but the impact was not significant in the multivariate analysis. The favorable outcome of DLBCL with HOTAIR high expression levels may be related to the negative correlation with c- MYC expression or c-MYC/BCL2 co-expression.
Conclusions
HOTAIR expression could be one of possible mechanisms for inducing H3K27me3 via EZH2-related PRC2 activation, and induced H3K27me3 may be strongly related to aggressive DLBCLs which show poor patient outcome.

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M. Winkle, J.L. Kluiver, A. Diepstra, A. van den Berg
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Case Study

Nodular Fasciitis of External Auditory Canal: Jihyun Ahn, Sunyoung Kim, Youngsil Park; J Pathol Transl Med. 2016;50(5):394-396. Published online June 6, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.11

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Abstract PDF

Nodular fasciitis is a pseudosarcomatous reactive process composed of fibroblasts and myofibroblasts, and it is most common in the upper extremities. Nodular fasciitis of the external auditory canal is rare. To the best of our knowledge, less than 20 cases have been reported to date. We present a case of nodular fasciitis arising in the cartilaginous part of the external auditory canal. A 19-year-old man complained of an auricular mass with pruritus. Computed tomography showed a 1.7 cm sized soft tissue mass in the right external auditory canal, and total excision was performed. Histologic examination revealed spindle or stellate cells proliferation in a fascicular and storiform pattern. Lymphoid cells and erythrocytes were intermixed with tumor cells. The stroma was myxoid to hyalinized with a few microcysts. The tumor cells were immunoreactive for smooth muscle actin, but not for desmin, caldesmon, CD34, S-100, anaplastic lymphoma kinase, and cytokeratin. The patient has been doing well during the 1 year follow-up period.

Citations

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Pathology Clinic: Nodular Fasciitis Involving the External Ear
Christina M. Yver, Michael A. Husson, Oren Friedman
Ear, Nose & Throat Journal.2023; 102(5): NP203. CrossRef
Nodular Fasciitis of the Nose and External Auditory Canal: Two Rare Case Reports
Wanjie Luo, Tianyu Ma, Siqi Wang, Xiaowei Qin, Li Jiang, Yuyao Wang, Tianhong Zhang
Ear, Nose & Throat Journal.2023; : 014556132211151. CrossRef
Nodular fasciitis of the external auditory canal: Clinical case report and review of the literature
Adrien Philippart, Jean-Christophe Degols, Jacques Vilain
Journal of Otology.2023; 18(4): 240. CrossRef
Diagnosis and Treatment of Nodular Fasciitis of Ear Region in Children: A Case Report and Review of Literature
Antonio Della Volpe, Paola Festa, Alfonso Maria Varricchio, Carmela Russo, Eugenio Maria Covelli, Delfina Bifano, Piera Piroli, Antonietta De Lucia, Arianna Di Stadio, Franco Ionna
Healthcare.2022; 10(10): 1962. CrossRef
A Case of Recurred Nodular Fasciitis in Supraauricular Region
Dong-Jo Kim, Seong-Wook Choi, Chung-Su Hwang, Hyun-Min Lee
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Original Article

Stromal Expression of MicroRNA-21 in Advanced Colorectal Cancer Patients with Distant Metastases: Kyu Sang Lee, Soo Kyung Nam, Jiwon Koh, Duck-Woo Kim, Sung-Bum Kang, Gheeyoung Choe, Woo Ho Kim, Hye Seung Lee; J Pathol Transl Med. 2016;50(4):270-277. Published online May 31, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.19

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Abstract PDF

Background
The aim of this study was to determine the regional heterogeneity and clinicopathological significance of microRNA-21 (miR-21) in advanced colorectal cancer (CRC) patients with distant metastasis.
Methods
miR-21 expression was investigated by using locked nucleic acid– fluorescence in situ hybridization in the center and periphery of the primary cancer and in distant metastasis from 170 patients with advanced CRC. In addition, α-smooth muscle actin and desmin were evaluated to identify cancer-associated fibroblasts (CAFs) by using immunohistochemistry.
Results
The miR-21 signal was observed in the cancer stroma. The expression of miR-21 (a score of 1–4) in the center and periphery of the primary cancer and in distant metastasis was observed in specimens from 133 (78.2%), 105 (61.8%), and 91 (53.5%) patients, respectively. miR-21 expression was heterogeneous in advanced CRC. Discordance between miR-21 expression in the center of the primary cancer and either the periphery of the primary cancer or distant metastasis was 31.7% or 44.7%, respectively. miR-21 stromal expression in the periphery of the primary cancer was significantly associated with a better prognosis (p=.004). miR-21 expression was significantly associated with CAFs in the center of the primary cancer (p=.001) and distant metastases (p=.041).
Conclusions
miR-21 expression is observed in cancer stroma related to the CAF quantity and frequently presents regional heterogeneity in CRC. Our findings indicate that the role of miR-21 in predicting prognosis may be controversial but provide a new perspective of miR-21 level measurement in cancer specimens.

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Review

Galectins: Double-edged Swords in the Cross-roads of Pregnancy Complications and Female Reproductive Tract Inflammation and Neoplasia: Nandor Gabor Than, Roberto Romero, Andrea Balogh, Eva Karpati, Salvatore Andrea Mastrolia, Orna Staretz-Chacham, Sinuhe Hahn, Offer Erez, Zoltan Papp, Chong Jai Kim; J Pathol Transl Med. 2015;49(3):181-208. Published online May 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.02.25

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Abstract PDF

Galectins are an evolutionarily ancient and widely expressed family of lectins that have unique glycan-binding characteristics. They are pleiotropic regulators of key biological processes, such as cell growth, proliferation, differentiation, apoptosis, signal transduction, and pre-mRNA splicing, as well as homo- and heterotypic cell-cell and cell-extracellular matrix interactions. Galectins are also pivotal in immune responses since they regulate host-pathogen interactions, innate and adaptive immune responses, acute and chronic inflammation, and immune tolerance. Some galectins are also central to the regulation of angiogenesis, cell migration and invasion. Expression and functional data provide convincing evidence that, due to these functions, galectins play key roles in shared and unique pathways of normal embryonic and placental development as well as oncodevelopmental processes in tumorigenesis. Therefore, galectins may sometimes act as double-edged swords since they have beneficial but also harmful effects for the organism. Recent advances facilitate the use of galectins as biomarkers in obstetrical syndromes and in various malignancies, and their therapeutic applications are also under investigation. This review provides a general overview of galectins and a focused review of this lectin subfamily in the context of inflammation, infection and tumors of the female reproductive tract as well as in normal pregnancies and those complicated by the great obstetrical syndromes.

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Original Article

Altered Expression of PTEN and Its Major Regulator MicroRNA-21 in Pulmonary Neuroendocrine Tumors: Hyoun Wook Lee, Seung Yeon Ha, Mee Sook Roh; Korean J Pathol. 2014;48(1):17-23. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.17

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Abstract PDF

Background

Phosphatase and tensin homolog on chromosome ten (PTEN) is one of the most frequently inactivated tumor suppressors in various tumor types. MicroRNA-21 (miR-21) may affect tumor progression by post-transcriptional repression of expression of tumor suppressors, such as PTEN. This study was conducted to evaluate the significance of PTEN expression in pulmonary neuroendocrine (NE) tumors and to analyze the relationship between PTEN and miR-21 expressions.

Methods

Expressions of PTEN and miR-21 were investigated by immunohistochemistry and real time reverse transcription-polymerase chain reaction, respectively, in 75 resected pulmonary NE tumors (23 typical carcinoids [TCs], nine atypical carcinoids [ACs], 22 large cell NE carcinomas [LCNECs], and 21 small cell lung carcinomas [SCLCs]).

Results

Loss of PTEN expression was observed in four of 23 TCs (17.4%), four of nine ACs (44.4%), 16 of 22 LCNECs (72.7%) and nine of 21 SCLCs (42.9%) (p=.025). The expression level of miR-21 was significantly higher in high-grade NE carcinomas than in carcinoid tumors (p<.001). PTEN expression was inversely correlated with miR-21 expression (p<.001).

Conclusions

This study suggests that aberrant expression of PTEN in relation to miR-21 may represent an important step in the development and progression of pulmonary NE tumors.

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