Journal of Pathology and Translational Medicine

Original Articles

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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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.

Citations

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Clinical application of cold atmospheric-pressure plasma: mechanisms and irradiation conditions
Eun Ji Jeong, Hyun Min Park, Dong Jae Lee, Jun Lee, Jun Yeong Cho, Kyung Deok Seo, Seokjun Je, Min Hyung Jung, Woo Yeon Hwang, Kyung Sook Kim
Journal of Physics D: Applied Physics.2024; 57(37): 373001. CrossRef
Aquaporins in Cancer Biology
Chul So Moon, David Moon, Sung Koo Kang
Frontiers in Oncology.2022;[Epub] CrossRef
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
Sukanta S. Bhattacharya, Brijesh Yadav, Ekta Yadav, Ariel Hus, Niket Yadav, Perminder Kaur, Lauren Rosen, Roman Jandarov, Jagjit S. Yadav
Frontiers in Physiology.2022;[Epub] CrossRef
Aquaporin water channels as regulators of cell-cell adhesion proteins
Sarannya Edamana, Frédéric H. Login, Soichiro Yamada, Tae-Hwan Kwon, Lene N. Nejsum
American Journal of Physiology-Cell Physiology.2021; 320(5): C771. CrossRef
Targeting Aquaporins in Novel Therapies for Male and Female Breast and Reproductive Cancers
Sidra Khan, Carmela Ricciardelli, Andrea J. Yool
Cells.2021; 10(2): 215. CrossRef
Targeting ion channels for the treatment of lung cancer
Liqin Zhang, Shuya Bing, Mo Dong, Xiaoqiu Lu, Yuancheng Xiong
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2021; 1876(2): 188629. CrossRef
Comprehensive Analysis of Aquaporin Superfamily in Lung Adenocarcinoma
Guofu Lin, Luyang Chen, Lanlan Lin, Hai Lin, Zhifeng Guo, Yingxuan Xu, Chanchan Hu, Jinglan Fu, Qinhui Lin, Wenhan Chen, Yiming Zeng, Yuan Xu
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
Cancers.2020; 12(7): 1911. CrossRef
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†
Guido Bellezza, Jacopo Vannucci, Fortunato Bianconi, Giulio Metro, Rachele Del Sordo, Marco Andolfi, Ivana Ferri, Paola Siccu, Vienna Ludovini, Francesco Puma, Angelo Sidoni, Lucio Cagini
Interactive CardioVascular and Thoracic Surgery.2017; 25(6): 856. CrossRef

Prognostic Implication of Semi-quantitative Immunohistochemical Assessment of CD20 Expression in Diffuse Large B-Cell Lymphoma: Chang Hwan Choi, Young Hoon Park, Joo Han Lim, Suk Jin Choi, Lucia Kim, In Suh Park, Jee Young Han, Joon Mee Kim, Young Chae Chu; J Pathol Transl Med. 2016;50(2):96-103. Published online February 15, 2016; DOI: https://doi.org/10.4132/jptm.2016.01.12

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Abstract PDF

Background
Immunohistochemical demonstration of CD20 in diffuse large B-cell lymphoma (DLBCL) is prerequisite not only for the diagnosis but also for assigning patients to rituximab-containing chemotherapy. However, little is known about the impact of abundance of CD20 expression assessed by immunohistochemistry on the clinical outcome of DLBCL. We performed a semi-quantitative immunohistochemical analysis of CD20 expression in DLBCL to examine the prognostic implication of the level of CD20 expression. Methods: Pre-treatment diagnostic tissue samples from 48 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen were represented in a tissue microarray and immunostained for CD20. The relative abundance of CD20 expression was semi-quantitatively scored using a web-based ImmunoMembrane plug-in. Receiver operating characteristic curve analysis was used to determine a prognostically relevant cut-off score in order to dichotomize the patients into CD20-high versus CD20-low groups. Results: The levels of CD20 expression were heterogeneous among the patients, with a wide and linear distribution of scores. Patients in CD20-low group showed significantly poor clinical outcome. Conclusions: The levels of CD20 expression in DLBCL are heterogeneous among the patients with DLBCL. A subgroup of the patients with CD20 expression levels below the cut-off score showed poor clinical outcome.

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The Expression Levels of CD20 as a Prognostic Value in Feline B-Cell Nasal Lymphoma: A Pilot Study
Kravee Chaipoca, Theerapol Sirinarumitr, Supreeya Srisampan, Charuwan Wongsali, Attawit Kovitvadhi, Tassanee Jaroensong
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Prognostic molecular biomarkers in diffuse large B-cell lymphoma in the rituximab era and their therapeutic implications
Sotirios G. Papageorgiou, Thomas P. Thomopoulos, Ioannis Katagas, Anthi Bouchla, Vassiliki Pappa
Therapeutic Advances in Hematology.2021;[Epub] CrossRef
Novel tumour–infiltrating lymphocyte-related risk stratification based by flow cytometry for patients with de novo angioimmunoblastic T cell lymphoma
Qiqi Zhu, Xueqin Deng, Wenqing Yao, Zihang Chen, Yunxia Ye, Limin Gao, Wenyan Zhang, Weiping Liu, Sha Zhao
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Induced CD20 Expression on B-Cell Malignant Cells Heightened the Cytotoxic Activity of Chimeric Antigen Receptor Engineered T Cells
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Juhyeon Jeong, Eun Ji Oh, Woo Ick Yang, Soo Jeong Kim, Sun Och Yoon
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Architectural patterns of p16 immunohistochemical expression associated with cancer immunity and prognosis of head and neck squamous cell carcinoma
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APMIS.2017; 125(11): 974. CrossRef
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Diffuse large B-cell lymphoma: R-CHOP failure—what to do?
Bertrand Coiffier, Clémentine Sarkozy
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Comparison of Analytical and Clinical Performance of HPV 9G DNA Chip, PANArray HPV Genotyping Chip, and Hybrid-Capture II Assay in Cervicovaginal Swabs: Ho Young Jung, Hye Seung Han, Hyo Bin Kim, Seo Young Oh, Sun-Joo Lee, Wook Youn Kim; J Pathol Transl Med. 2016;50(2):138-146. Published online January 13, 2016; DOI: https://doi.org/10.4132/jptm.2015.10.21

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Abstract PDF

Background
Human papillomavirus (HPV) infection can be detected by using several molecular methods, including Hybrid-Capture II (HC2) assay and variable HPV DNA chip tests, although each method has different sensitivities and specificities. Methods: We performed HPV 9G DNA Chip (9G) and PANArray HPV Genotyping Chip (PANArray) tests on 118 cervicovaginal swabs and compared the results with HC2, cytology, histology, and direct sequencing results. Results: The overall and high-risk HPV (HR-HPV) positivity rates were 62.7% and 44.9% using 9G, and 61.0% and 30.5% using PANArray, respectively. The positivity rates for HR-HPV with these two chips were significantly lower than 55.1% when HC2 was used. The sensitivity of overall HPV positivity in detecting histologically confirmed low-grade cervical squamous intraepithelial lesions or higher was 88.7% for all three tests. The specificity was 58.5% for 9G and 61.5% for PANArray, which was significantly lower than the 72.3% for HC2. With the HR-HPV⁺ genotype threshold, the sensitivity decreased to 75.5% for 9G and 52.8% for PANArray, which was significantly lower than the 88.7% for HC2. Comparison of the two chips showed concordant results in 55.1% of the samples, compatible results in 16.9%, and discordant results in 28.0%, exhibiting poor agreement in detecting certain HPV genotypes. Compared with direct sequencing, 9G yielded no discordant results, whereas PANArray yielded 31 discordant results (26.7%). Conclusions: Compared with HC2, the HPV genotyping tests showed lower sensitivity in histologic correlation. When the two chips were compared, the 9G was more sensitive and accurate for detecting HR-HPV than the PANArray.

Citations

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Concordance of Anyplex™ II HPV HR assays with reference HPV assays in cervical cancer screening: Systematic review
Habtamu Biazin
Journal of Virological Methods.2022; 301: 114435. CrossRef
The clinical performance of human papillomavirus genotyping using PANArray HPV chip: Comparison to ThinPrep cytology alone and co-testing
Jiyoung Kim, Sun-Young Jun, Lee-So Maeng
Pathology - Research and Practice.2020; 216(9): 153121. CrossRef
Analytic performance of PANArray HPV and HPV 9G DNA chip tests for genotyping of high-risk human papillomavirus in cervical ThinPrep PreservCyt samples
Jiyoung Kim, Sun-Young Jun, Magdalena Grce
PLOS ONE.2019; 14(10): e0224483. CrossRef

In-house Manual Construction of High-Density and High-Quality Tissue Microarrays by Using Homemade Recipient Agarose-Paraffin Blocks: Kyu Ho Kim, Suk Jin Choi, Yeon Il Choi, Lucia Kim, In Suh Park, Jee Young Han, Joon Mee Kim, Young Chae Chu; Korean J Pathol. 2013;47(3):238-244. Published online June 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.238

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Abstract PDF

Background

Self-made tissue punches can be effectively used to punch holes in blank recipient paraffin blocks and extract tissue cores from the donor paraffin blocks for the low-cost construction of tissue microarrays (TMAs). However, variable degrees of section distortion and loss of the tissue cores can occurs during cutting of the TMAs, posing technical problems for in-house manual construction of high-density TMAs. We aimed to update the method for in-house manual TMA construction to improve the quality of high-density TMAs.

Methods

Blocks of agarose gel were subjected to the standard tissue processing and embedding procedure to prepare recipient agarose-paraffin blocks. The self-made tissue punches and recipient agarose-paraffin blocks were used to construct TMAs, which were completely melted and re-embedded in paraffin to make finished TMA blocks.

Results

The donor tissue cores were completely integrated into the surrounding paraffin of the recipient blocks. This method enabled us to construct high-density TMAs with significantly less section distortion or loss of tissue cores during microtomy.

Conclusions

Simple and inexpensive construction of high-density and high-quality TMAs can be warranted by using paraffinized agarose gels as recipient blocks.

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Yi-Jing Chen, Chun-Mei Yang, Jiang-Sheng Huang, Ping Wang, Yan-Hua Lv, Cheng Tang, Wei Deng
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Optimization of Tissue Microarrays from Banked Human Formalin-Fixed Paraffin Embedded Tissues in the Cancer Research Setting
Tammy Sexton, Gregory L. Kucera, Edward A. Levine, Kounosuke Watabe, Stacey S. O'Neill
Biopreservation and Biobanking.2019; 17(5): 452. CrossRef
Monocarboxylate transporters MCT1 and MCT4 are independent prognostic biomarkers for the survival of patients with clear cell renal cell carcinoma and those receiving therapy targeting angiogenesis
Yan-Wei Cao, Yong Liu, Zhen Dong, Lei Guo, En-Hao Kang, Yong-Hua Wang, Wei Zhang, Hai-Tao Niu
Urologic Oncology: Seminars and Original Investigations.2018; 36(6): 311.e15. CrossRef
Platelet-derived growth factor receptor α in hepatocellular carcinoma is a prognostic marker independent of underlying liver cirrhosis
Jung-Hwan Yu, Joon Mee Kim, Ja Kyung Kim, Suk Jin Choi, Kwan Sik Lee, Jin-Woo Lee, Hye Young Chang, Jung Il Lee
Oncotarget.2017; 8(24): 39534. CrossRef
Prognostic Implication of Semi-quantitative Immunohistochemical Assessment of CD20 Expression in Diffuse Large B-Cell Lymphoma
Chang Hwan Choi, Young Hoon Park, Joo Han Lim, Suk Jin Choi, Lucia Kim, In Suh Park, Jee Young Han, Joon Mee Kim, Young Chae Chu
Journal of Pathology and Translational Medicine.2016; 50(2): 96. CrossRef
High Quality Tissue Miniarray Technique Using a Conventional TV/Radio Telescopic Antenna
Mohamed A. Elkablawy, Abdulkader M. Albasri
Asian Pacific Journal of Cancer Prevention.2015; 16(3): 1129. CrossRef

Construction of High-Density Tissue Microarrays at Low Cost by Using Self-Made Manual Microarray Kits and Recipient Paraffin Blocks: Chang Hwan Choi, Kyu Ho Kim, Ju Young Song, Suk Jin Choi, Lucia Kim, In Suh Park, Jee Young Han, Joon Mee Kim, Young Chae Chu; Korean J Pathol. 2012;46(6):562-568. Published online December 26, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.562

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Abstract PDF

Background

Advances of tissue microarray (TMA) technology have enabled simultaneous in situ analysis of biomarker expression in a large number of archived pathology specimens. However, the relatively high cost of TMA construction may hamper many researchers from using this essential tool of modern pathology research. We discuss methods for making TMA kits and recipient blocks for manual construction of high-density TMAs at low cost.

Methods

Ordinary cannula piercing needles, hypodermic needles, bone marrow biopsy needles, metallic ink cartridges of ballpoint pens, and disposable skin biopsy punches were used to construct self-made manual TMA kits. The recipient blocks were manufactured by boring holes in the conventional bare paraffin blocks. A mini electric hand drill and a microcompound table assembled on a drill stand were used to maximize the capacity of the recipient blocks.

Results

By using TMA kits made from cannula piercing needles (16- and 18-gauge), it was possible to construct TMAs with 1 mm×140 cores, 0.6 mm×320 cores, 2 mm×70 cores, 3 mm×35 cores, and 5 mm×12 cores. The capacity of the recipient blocks could be dramatically increased by drilling holes.

Conclusions

Construction of TMAs using self-made TMA kits is an inexpensive alternative to construction of TMAs using commercial devices.

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Constructing high-density tissue microarrays with a novel method and a self-made tissue-arraying instrument
Ping Qin, Liu Li, Li Zhao, Piaopiao Bian, Zhongtang Xiong
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The correlation of PD-L1 expression in cytological and histological material of serous high-grade ovarian cancer
Ljubiša Jovanović, Anđa Ćirković, Ljubinka Nikolić, Milena Jović, Darko Mikić, Svetlana Milenković, Radmila Janković
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Expression of estrogen and progesterone receptors, HER2 protein and Ki-67 proliferation index in breast carcinoma in both tumor tissue and tissue microarray
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PD-L1 Expression in Different Segments and Histological Types of Ovarian Cancer According to Lymphocytic Infiltrate
Ljubiša Jovanović, Radmila Janković, Andja Ćirković, Milena Jović, Tijana Janjić, Slaviša Djuričić, Svetlana Milenković
Medicina.2021; 57(12): 1309. CrossRef
Optimization of Tissue Microarrays from Banked Human Formalin-Fixed Paraffin Embedded Tissues in the Cancer Research Setting
Tammy Sexton, Gregory L. Kucera, Edward A. Levine, Kounosuke Watabe, Stacey S. O'Neill
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Alessandra Sfacteria, Laura Perillo, Francesco Macrì, Giovanni Lanteri, Claudia Rifici, Giuseppe Mazzullo
Veterinary Quarterly.2015; 35(3): 170. CrossRef
High Quality Tissue Miniarray Technique Using a Conventional TV/Radio Telescopic Antenna
Mohamed A. Elkablawy, Abdulkader M. Albasri
Asian Pacific Journal of Cancer Prevention.2015; 16(3): 1129. CrossRef
Overview on Techniques to Construct Tissue Arrays with Special Emphasis on Tissue Microarrays
Ulrich Vogel
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Tissue Microarray
Kathleen Barrette, Joost J. van den Oord, Marjan Garmyn
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Hyoun Wook Lee, Seung Yeon Ha, Mee Sook Roh
Korean Journal of Pathology.2014; 48(1): 17. CrossRef
Optimizing tissue microarray construction procedure to improve quality of sections
Hua Chang, Diane Peluso, Sadiq Hussain, Michail Shipitsin, Peter Blume-Jensen
Journal of Histotechnology.2014; 37(3): 95. CrossRef
In-house Manual Construction of High-Density and High-Quality Tissue Microarrays by Using Homemade Recipient Agarose-Paraffin Blocks
Kyu Ho Kim, Suk Jin Choi, Yeon Il Choi, Lucia Kim, In Suh Park, Jee Young Han, Joon Mee Kim, Young Chae Chu
Korean Journal of Pathology.2013; 47(3): 238. CrossRef

Immunohistochemical Array for Clear Cell Type Mucoepidermoid Carcinoma.: Yeon Sook Kim, Sang Shin Lee, Ji Yong Song, Eun Cheol Kim, Suk Keun Lee; Korean J Pathol. 2010;44(3):284-294.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.284

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Abstract PDF

BACKGROUND
The protein expression profile of clear cell type mucoepidermoid carcinoma (MEC) is not well known.
METHODS
We examined a case of clear cell type MEC by immunohistochemical (IHC) array using 59 antibodies against oncoproteins, proliferation-related proteins, apoptosis-related proteins, growth factor-related proteins, angiogenesis-related proteins, and matrix proteins.
RESULTS
MEC tumor cells showed 40 to 60% more expression of BCL-2 and cyclin-dependent kinase 4 than normal gingival tissue, and 20-40% more expression of BCL-2-associated agonist of cell death, deleted in malignant brain tumors 1, E-cadherin, eIF5A, hypoxia-inducible factor, vimentin, and Wnt-1. Expression of other proteins, including p53, epidermal growth factor receptor, proliferating cell nuclear antigen, survivin, carcinoembryonic antigen, beta-catenin, poly-ADP ribose-polymerase, etc. were relatively weak in MEC tumor cells.
CONCLUSIONS
The IHC array for our MEC contained strong oncogenic signals involving Wnt-1/adenomatous polyposis coli, tumor necrosis factor a/signal transducer and activator of transcription 3/BCL-2, and pAKT pathways, signals that could result in the prolonged survival of clear tumor cells.

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Ji-Sook Jung, Ho-Won Park, Ju-Hyun Lee, Hyun-Woo Seo, Suk-Keun Lee
THE JOURNAL OF THE KOREAN ACADEMY OF PEDTATRIC DENTISTRY.2011; 38(3): 296. CrossRef

Gene Expression Profiles of Uterine Normal Myometrium and Leiomyoma and Their Estrogen Responsiveness In Vitro.: Eun Ju Lee, Prati Bajracharya, Dong Mok Lee, Kyung Hyun Cho, Keuk Jun Kim, Young Kyung Bae, Mi Jin Kim, Ki Ho Lee, Hang Jin Kim, Gun Ho Song, Sang Sik Chun, Inho Choi; Korean J Pathol. 2010;44(3):272-283.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.272

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Abstract PDF

BACKGROUND
Uterine leiomyomas are common benign smooth muscle tumors among the reproductive aged-women. The research has been aimed to identify the differentially expressed genes between normal myometrium and leiomyoma and to investigate the effects of E2 on their expression.
METHODS
Gene microarray analysis was performed to identify the differentially expressed genes between normal myomerium and leiomyoma. The data was confirmed at protein level by tissue microarray.
RESULTS
Gene microarray analysis revealed 792 upregulated genes in leiomyoma. Four genes (tropomyosin 4 [TPM4], collagen, type IV, alpha 2 [COL4alpha2], insulin-like growth factor binding protein 5 [IGFBP5], tripartite motif-containing 28 [TRIM28]) showed the most dramatic upregulation in all leiomyoma samples. Tissue microarray analyses of 262 sample pairs showed significantly elevated expression of TPM4, IGFBP5, estrogen receptor-alpha, and progesterone receptor (PR) protein in leiomyoma from the patients in their forties, COL4alpha2 in the forties and fifties age-groups, and TRIM28 in the thirties age-group. PR, insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R) and IGFBP5 were induced by E2 in in vitro culture of tissue explants from which cells migrated throughout the plate. Among these, PR, IGF-1, IGFBP5 genes showed higher expression in tissue compared to cells-derived from tissue in leiomyoma and IGF-1R in leiomyoma cell.
CONCLUSIONS
This observation implies the importance of the whole tissue context including the cells-derived from tissue in the research for the understanding of molecular mechanism of leiomyoma. Here, we report higher expression of TRIM28 in leiomyoma for the first time and identify E2-responsive genes that may have important roles in leiomyoma development.

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Common fibroid-associated genes are differentially expressed in phenotypically dissimilar cell populations isolated from within human fibroids and myometrium
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The Analysis and Clinical Usefulness of HPV DNA Chip Test in the Uterine Cervix.: Joo hyeon Jeong, Hyun Yee Cho, Na Rae Kim, Dong Hae Chung, Sanghui Park, Seung Yeon Ha; Korean J Pathol. 2010;44(1):77-82.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.77

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Abstract PDF

BACKGROUND
The genotypes of human papillomavirus (HPV) are important in carcinogenesis in uterine cervical cancer and may be different in geographic distribution.
METHODS
In 2,086 women, we analyzed the prevalence of HPV and HPV genotypes in uterine cervix by HPV-DNA chip test (n = 2,086), cytology (PAP smear, n = 1997) and biopsy (n = 546).
RESULTS
Of the 2,086 cases, 1,019 cases (48.8%) were HPV-positive and 1,067 cases (51.2%) were negative for HPV. Single infection occurred most commonly (72.1% of women). HPV genotypes in the high-risk and low-risk groups, respectively were HPV-16/-58/-18/-52/-53 and HPV-70/-6/-11. The detection rates of HPV-70 in subjects older than 50 years increased significantly (p < 0.05). Infection in high risk subjects was detected in high grade lesions compared with infection in low risk subjects (p < 0.05).
CONCLUSIONS
HPV-16/-58/-18/-52/-53/-70/-6/-11 genotypes were common in the patient group similar to findings in East Asia. HPV-70 infection is predominant in those older than 40 years.

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Current Status of and Perspectives on Cervical Cancer Screening in Korea
Sung-Chul Lim, Chong Woo Yoo
Journal of Pathology and Translational Medicine.2019; 53(4): 210. CrossRef
Cervical cytology of atypical squamous cells, cannot exclude high-grade squamous intra-epithelial lesion: significance of age, human papillomavirus DNA detection and previous abnormal cytology on follow-up outcomes
Chang Ohk Sung, Young Lyun Oh, Sang Yong Song
European Journal of Obstetrics & Gynecology and Reproductive Biology.2011; 159(1): 155. CrossRef
Cytomorphologic Features According to HPV DNA Type in Histologically Proven Cases of the Uterine Cervix
In Ho Choi, So-Young Jin, Dong Wha Lee, Dong Won Kim, Yoon Mi Jeen
The Korean Journal of Pathology.2011; 45(6): 612. CrossRef

Molecular Subtypes of Primary Glioblastoma Identified by Gene Expression Profiling.: Ghee Young Choe, S Mischel Paul; Korean J Pathol. 2002;36(5):328-337.

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Abstract PDF: BACKGROUND
The over-expression of the epidermal growth factor receptor (EGFR) occurs in nearly 50% of primary glioblastoma multiforme (GBM). Disruption of multiple signaling pathways is a critical factor in regulating the biological and clinical behavior of GBMs. In the future, therapy that specifically targets these disrupted pathways may represent the best potential treatment for patients with GBM. Large scale gene expression profiling provides a powerful approach to identify these disrupted genetic pathways and to uncover previously unknown molecular subtypes.
METHODS
We used 13 cases of primary GBM biopsy samples obtained from untreated patients and Affymetrix high-density oligonucleotide arrays to identify novel subsets of primary GBMs.
RESULTS
We showed that the expression of 90 genes differentiate EGFR+ from EGFR non-expressing (EGFR-) de novo GBMs, including expression of a number of potentially targetable molecules that act as growth/survival factors for GBMs. We also demonstrated the presence of two additional molecular subtypes of primary GBMs, including one characterized by the coordinate upregulation of contiguous genes on chromosome 12q13-15, which has a distinct global gene expression profile and expresses both astrocytic and oligodendroglial genes.
CONCLUSION
We have shown that there are EGFR+ primary GBMs, GBMs with coordinate upregulation of genes on chromosome 12q13-15, and primary GBMs lacking either alteration. Moreover, they have distinct transcriptional profiles. Our findings strongly suggest that the three GBMs are biologically different tumor types, despite their identical microscopic appearance, and provide an important first step in developing a molecular taxonomy of GBMs.

Reduced Expression of Claudin-7 Correlates with Invasiveness and Nuclear Grade of Breast Carcinomas.: Sang Hee Seok, Su Hwan Kang, Soo Jung Lee, Tae Yoon Hwang, Young Kyung Bae; Korean J Pathol. 2007;41(3):158-164.

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Abstract PDF: Background
: Claudins are important components of the tight junctions in the intercellular barriers and cell polarity. Among them, claudin-7 is down-regulated in breast cancers compared with the normal breast epithelium. The aim of this study was to determine the expression pattern and prognostic value of claudin-7 in breast carcinomas.
Methods
: Claudin-7 expression was evaluated immunohistochemically in 42 cases of ductal carcinoma in situ (DCIS) and in 142 cases of invasive breast carcinoma (IBC) using a tissue microarray (TMA).
Results
: Claudin- 7 was strongly expressed in the normal luminal epithelial cells in the breast lobule. The level of claudin-7 expression was significantly lower or absent in 45.2% (19/42) of DCIS and 72.5% (103/142) of IBC. A loss or reduced expression of claudin-7 correlated with the invasiveness (p=0.001) of breast carcinomas and a high nuclear grade (p=0.013) in IBC.
Conclusion
Claudin-7 is an important tight junction protein in the breast and a loss of expression may assist in the dissociation and invasion of tumor cells.

Expression of CD44 Isoforms and Its Significance in Renal Cell Carcinoma.: Ghil Suk Yoon, Hee Yeon Hong, Tae Sook Kim; Korean J Pathol. 2005;39(4):251-257.

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Abstract PDF: Background
: CD44 is a transmembranous glycoprotein that participates in cell-cell and cell-matrix interactions, and it also contributes to cell migration. In vitro studies have suggested that the expression of CD44 isoforms is associated with tumor metastasis. Since it is not clear whether the CD44 isoforms play a role in the tumorigenesis, differentiation, progression or metastasis of renal cell carcinomas (RCCs). Methods : We performed immunohistochemistry with primary antibodies for the standard CD44 (CD44s) and the CD44 variant exon 6 (CD44v6) on the archival paraffin-embedded tissue microarray (TMA) specimens from 51 RCC patients. Results : In the normal kidney, the expressions of both CD44s and CD44v6 were negligible. The CD44s expression was increased in accordance with the tumor size (p<0.01), but it was not related to the microvessel density (MVD). No CD44v6 expression was observed in all RCC cases. Univariate analysis indicated that stage, tumor size, lymph node metastasis and distant organ metastasis were the statistically significant prognostic factors for disease free survival (DFS) (p<0.01), and the multivariate analysis proved that stage (p<0.01) and tumor size (p<0.05) were the independent prognostic factors for DFS. Conclusions : Our results suggest that CD44s, but not CD44v6, plays a role in tumor progression and it could be a potential prognostic factor for patients with RCCs.

Tissue Microarray Analysis of the Expression of p53, c-kit and CD34 in Sarcomas.: Jinyoung Yoo, Kyung Shin Park, Seok Jin Kang, Chang Suk Kang; Korean J Pathol. 2004;38(4):221-227.

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Abstract PDF: BACKGROUND
Our objectives in this study were to (1) evaluate the possible role of p53, c-kit and CD34 proteins in sarcomas and to determine their potential relationship; (2) use a tissue microarray to compare the immunohistochemical staining results on both the tissue microarrays and the corresponding whole tissue sections.
METHODS
Whole sections from 85 sarcomas were studied for the immunohistochemical expression of p53, c-kit and CD34. Tissue microarrays consisting of triplicate 2 mm cores from the corresponding blocks were constructed and stained according to the same protocols as those used for the whole sections.
RESULTS
On whole section analysis, p53 protein was expressed in 25 cases (29.4%). Expression of c-kit was observed in 31 specimens (36.5%), whereas CD34 expression was noted in 11 tumors (12.9%). The overall concordance between triplicates was 96% (217/226). The consensus score from the combined triplicates agreed with the results on the whole sections at 91.4% (233/255). The correlations between p53 and CD34, and between c-kit and CD34, were statistically significant (p=.028 and p=.010 respectively).
CONCLUSIONS
p53 and c-kit express relatively frequently in sarcomas. Tissue microarrays are an effective alternative to whole sections; however, the presence of triplicate punches seems to improve the yield but not the concordance of data.

Analysis of Gene Expression in Renal Cell Carcinomas Using cDNA Microarray: Reduced Expression of Decorin in Renal Cell Carcinomas.: Jin Sook Lee, Kang Suek Suh, Kyung Un Choi, Jee Yeun Kim, Do Youn Park; Korean J Pathol. 2003;37(4):232-238.

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Abstract PDF: BACKGROUND
Identification of the genes expressed differentially in renal cell carcinoma (RCC)but not in the non-cancerous kidney is important for understanding the molecular basis ofrenal cell carcinoma and for defining possible prognostic value and therapeutic intervention.We investigated the changes in gene expression accompanying the development and progression of kidney cancer by cDNA microarrays.
METHODS
To identify molecular alterations in renal cell carcinoma, we measured expression profiles for paired neoplastic and noncancerouskidney samples from an individual by means of a cDNA microarry representing 7, 500genes. Of the differentially expressed genes, we assessed the decorin gene at the proteinlevel using immunohistochemistry.
RESULTS
The 60 genes were noted to have more than a fivefold change in expression (either increased or decreased) in RCC compared to the noncancerouskidney. The changed genes are those associated with signal transduction, metabolizingenzymes, the cytoskeleton, cell adhesion, cell cycle control, modulation of transcription, the tumor suppressor gene and tumor antigens. Under immunohistochemistry, the expressionof decorin was significantly decreased in the tumor than in the non-cancerous kidney.The expression rate of decorin was not associated with the patient's sex, age, histologic type, Fuhrmann nuclear grade and T stage.
CONCLUSION
The author predicted that these geneexpression profiling experiments will lead to improvements in the basic understanding of renaltumor pathogenesis and will promote the discovery of novel molecular markers for renal tumordiagnosis and therapy.

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