Journal of Pathology and Translational Medicine

Original Articles

Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer: Sujin Park, Junsik Kim, Woncheol Jang, Kyoung-Mee Kim, Kee-Taek Jang; J Pathol Transl Med. 2023;57(2):113-122. Published online March 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.02.01

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Background
Gallbladder cancer (GBC) is usually detected in advanced stages with a low 5-year survival rate. Delta-like ligand 4 (DLL4), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-2alpha (HIF2α) have been studied for their role in tumorigenesis and potential for therapeutic target, and multiple clinical trials of the agents targeting them are ongoing. We investigated the expression of these markers in surgically resected GBC and tried to reveal their association with the clinicopathologic features, mutual correlation of their expression, and prognosis of the GBC patients by their expression.
Methods
We constructed the tissue microarray blocks of 99 surgically resected GBC specimens and performed immunohistochemistry of DLL4, VEGF, and HIF2α. We used the quantitative digital image analysis to evaluate DLL4 and VEGF expression, while the expression of HIF2α was scored manually.
Results
The expression of VEGF and HIF2α showed a significant trend with tumor differentiation (p= .028 and p= .006, respectively). We found that the high DLL4 and VEGF expression were significantly correlated with lymph node metastasis (p= .047, both). The expression of VEGF and HIF2α were significantly correlated (p < .001). The GBC patients with low HIF2α expression showed shorter recurrence-free survival than those with high HIF2α expression.
Conclusions
This study suggested the possibility of the usage of DLL4 and VEGF to predict the lymph node metastasis and the possibility of VEGF and HIF2α to predict the expression level mutually. Further studies may be needed to validate our study results and eventually accelerate the introduction of the targeted therapy in GBC.

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Dedifferentiated Leiomyosarcoma of the Uterine Corpus with Heterologous Component: Clinicopathological Analysis of Five Consecutive Cases from a Single Institution and Comprehensive Literature Review
Suyeon Kim, Hyunsik Bae, Hyun-Soo Kim
Diagnostics.2024; 14(2): 160. CrossRef
Identification of Key Immune Infiltration Related Genes Involved in Aortic Dissection Using Bioinformatic Analyses and Experimental Verification
Lin Zheng, Yusi Yang, Jie Liu, Tianliang Zhao, Xin Zhang, Lihua Chen
Journal of Inflammation Research.2024; Volume 17: 2119. CrossRef

Serous Adenocarcinoma of Fallopian Tubes: Histological and Immunohistochemical Aspects: Natalia Hyriavenko, Mykola Lyndin, Kateryna Sikora, Artem Piddubnyi, Ludmila Karpenko, Olha Kravtsova, Dmytrii Hyriavenko, Olena Diachenko, Vladyslav Sikora, Anatolii Romaniuk; J Pathol Transl Med. 2019;53(4):236-243. Published online April 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.03.21

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Abstract PDF

Background
Although primary cancer of the fallopian tubes is a relatively rare type of tumor in female reproductive organs, its mortality is quite high. It is important to identify molecular and biological markers of this malignancy that determine its specific phenotype.
Methods
The study was carried out on samples received from 71 female patients with primary cancer of the fallopian tubes. The main molecular and biological properties, including hormone status (estrogen receptor [ER], progesterone receptor [PR]), human epidermal growth factor receptor (HER2)/neu expression, proliferative potential (Ki-67), apoptosis (p53, Bcl-2), and pro-angiogenic (vascular endothelial growth factor) quality of serous tumors were studied in comparison with clinical and morphological characteristics.
Results
ER and PR expression is accompanied by low grade neoplasia, early clinical disease stage, and absence of lymphogenic metastasis (p < .001). HER2/neu expression is not typical for primary cancer of the fallopian tubes. Ki-67 expression is characterized by an inverse correlation with ER and PR (p < .05) and is associated with lymphogenic metastasis (p < .01). p53+ status correlates with high grade malignancy, tumor progression, metastasis, negative ER/PR (p < .001), and negative Bcl-2 status (p < .05). Positive Bcl-2 status is positively correlated with ER and PR expression and low grade malignancy.
Conclusions
Complex morphologic (histological and immunohistochemical) study of postoperative material allows estimation of the degree of malignancy and tumor spread to enable appropriate treatment for each case.

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Rare non-serous fallopian tube cancers: institutional experience and literature review
Dmitrii Sumtsov, Georgyi Sumtsov, Nataliia Hyriavenko, Mykola Lyndin, Kateryna Sikora, Nataliia Kalashnik, Svitlana Smiian, Igor Gladchuk
Wiener Medizinische Wochenschrift.2024; 174(9-10): 199. CrossRef
UŞAQLIQ BORULARININ BİRİNCİLİ XƏRÇƏNGİ: DİAQNOSTİKASI VƏ MÜALİCƏSİNİN NƏTİCƏLƏRİ
D.G. Sumtsov, G.O. Sumtsov, N.I. Hyriavenko, S.A. Smiian, N.V. Kalashnyk, K.O. Sikora, N.M. Rozhkovska, I.Z. Gladchuk
Azerbaijan Medical Journal.2023; (4): 75. CrossRef
FEATURES OF ENDOMETRIUM STRUCTURE IN ALCOHOL-ABUSING HIV-INFECTED INDIVIDUALS
M. Lytvynenko
Inter Collegas.2021; 8(1): 52. CrossRef
Concurrent Clostridial Enteritis and Oviductal Adenocarcinoma with Carcinomatosis in an Adult Alpaca (Vicugna pacos)
Mandy Womble, Megan E. Schreeg, Allison Hoch, Enoch B. de Souza Meira, Derek Foster, Christopher Premanandan, Tatiane T. Negrão Watanabe
Journal of Comparative Pathology.2021; 189: 52. CrossRef
Problems of primary fallopian tube cancer diagnostics during and after surgery
D.G. Sumtsov, I.Z. Gladchuk, G.O. Sumtsov, N.I. Hyriavenko, M.S. Lyndin, V.V. Sikora, V.M. Zaporozhan
REPRODUCTIVE ENDOCRINOLOGY.2021; (59): 66. CrossRef

The Potential Roles of MELF-Pattern, Microvessel Density, and VEGF Expression in Survival of Patients with Endometrioid Endometrial Carcinoma: A Morphometrical and Immunohistochemical Analysis of 100 Cases: Dmitry Aleksandrovich Zinovkin, Md Zahidul Islam Pranjol, Daniil Rudolfovich Petrenyov, Eldar Arkadievich Nadyrov, Oleg Gennadievich Savchenko; J Pathol Transl Med. 2017;51(5):456-462. Published online September 14, 2017; DOI: https://doi.org/10.4132/jptm.2017.07.19

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Abstract PDF

Background
In this study, we hypothesized that microcystic, elongated, fragmented (MELF)-pattern, vascular endothelial growth factor (VEGF) expression by cancer cells and microvessel density of cancer stroma may be associated with progression of endometrioid adenocarcinoma. Methods: The study used data from the Belarus Cancer Registry and archival histological material of 100 patients with retrospectively known good (survival) and poor (disease progression and death) outcomes. All cases were immunohistochemically stained for CD34 and VEGF. Two independent samples were compared for the characteristics of signs, and obtained results were analyzed by receiver operating characteristic analysis, Mann-Whitney U test, χ² test (Yates correction), and Mantel-Cox test. Multivariate Cox hazard analysis and Spearman correlation test were used. A p-value of less than .05 was considered statistically significant. Results: The observed survival rate of patients with endometrioid adenocarcinoma was significantly lower (p = .002) in MELF-pattern positive patients when compared with MELF-pattern negative patients. The overall survival rate of patients whose tumors had more than 114 vessels/mm² of tissue was significantly low (p < .001). Interestingly, a similar observation was found in patients with increased vessel area, evidenced by VEGF expression in the glandular tumor component. Conclusions: Our study suggests, for the first time, that these criteria may be used as risk factors of endometrioid adenocarcinoma progression during 5 years after radical surgical treatment. However, a large independent cohort of samples should be considered in the future to validate our findings.

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Molecular Classification of Endometrial Endometrioid Carcinoma With Microcystic Elongated and Fragmented Pattern
Baohui Ju, Jianghua Wu, Lin Sun, Chunrui Yang, Hu Yu, Quan Hao, Jianmei Wang, Huiying Zhang
International Journal of Gynecological Pathology.2024; 43(3): 233. CrossRef
Association of Local and Distant Organ Metastases With MELF Pattern in Endometrial Cancer
Varol Gülseren, Ertuğrul Şen, Mehmet Dolanbay, Fulya Çağli, Nahit Topaloğlu, Figen Öztürk, Bülent Özçelik, Serdar Serin, Kemal Güngördük
International Journal of Gynecological Pathology.2024;[Epub] CrossRef
The vasculogenic mimicry, CD146 + and CD105 + microvessel density in the prognosis of endometrioid endometrial adenocarcinoma: a single-centre immunohistochemical study
Dmitry A. Zinovkin, Hongbo Wang, Zhicheng Yu, Qian Zhang, Yang Zhang, Sitian Wei, Ting Zhou, Qi Zhang, Jun Zhang, Eldar A. Nadyrov, Abdullah Farooq, Yulia Lyzikova, Ilya V. Vejalkin, Irina I. Slepokurova, Md Zahidul Islam Pranjol
Biomarkers.2024; : 1. CrossRef
Dynamic contrast-enhanced MR imaging of uterine endometrial carcinoma with/without squamous differentiation
Mayumi Takeuchi, Kenji Matsuzaki, Yoshimi Bando, Masafumi Harada
Abdominal Radiology.2023; 48(8): 2494. CrossRef
Role of adipocytokines in endometrial cancer progression
Ran Li, Fang Dong, Ling Zhang, Xiuqin Ni, Guozhi Lin
Frontiers in Pharmacology.2022;[Epub] CrossRef
Endometrial carcinoma: use of tracer kinetic modeling of dynamic contrast-enhanced MRI for preoperative risk assessment
Zhijun Ye, Gang Ning, Xuesheng Li, Tong San Koh, Huizhu Chen, Wanjing Bai, Haibo Qu
Cancer Imaging.2022;[Epub] CrossRef
Microcystic elongated and fragmented (MELF) pattern of invasion: Molecular features and prognostic significance in the PORTEC-1 and -2 trials
A.S.V.M. van den Heerik, K.T.S. Aiyer, E. Stelloo, I.M. Jürgenliemk-Schulz, L.C.H.W. Lutgens, J.J. Jobsen, J.W.M. Mens, E.M. van der Steen-Banasik, C.L. Creutzberg, V.T.H.B.M. Smit, N. Horeweg, T. Bosse
Gynecologic Oncology.2022; 166(3): 530. CrossRef
Pathological features, immunoprofile and mismatch repair protein expression status in uterine endometrioid carcinoma: focus on MELF pattern of myoinvasion
Angela Santoro, Giuseppe Angelico, Frediano Inzani, Saveria Spadola, Damiano Arciuolo, Michele Valente, Teresa Musarra, Giovanni Capelli, Francesco Fanfani, Valerio Gallotta, Giovanni Scambia, Gian Franco Zannoni
European Journal of Surgical Oncology.2021; 47(2): 338. CrossRef
Prognostic impact of tumor budding in endometrial carcinoma within distinct molecular subgroups
Tilman T. Rau, Eva Bettschen, Carol Büchi, Lucine Christe, Amanda Rohner, Michael D. Müller, Joseph W. Carlson, Sara Imboden, Inti Zlobec
Modern Pathology.2021; 34(1): 222. CrossRef
Sentinel Nodal Metastasis Detection in Endometrial Carcinoma With Microcystic, Elongated, and Fragmented (MELF) Pattern by Cytokeratin Immunostaining
Kimmie M Rabe, Molly E Klein, Sayak Ghatak, Irina Stout, Alexandra Schefter, Britt K Erickson, Mahmoud A Khalifa
American Journal of Clinical Pathology.2021; 156(5): 846. CrossRef
Patterns of Myometrial Invasion in Endometrial Adenocarcinoma with Emphasizing on Microcystic, Elongated and Fragmented (MELF) Glands Pattern: A Narrative Review of the Literature
Svetlana Mateva, Margarita Nikolova, Angel Yordanov
Diagnostics.2021; 11(9): 1707. CrossRef
Increase in FoxP3, CD56 immune cells and decrease in glands PGRMC1 expression in the endometrium are associated with recurrent miscarriages
Yulia Anatolievna Lyzikova, Dmitry Aleksandrovich Zinovkin, Md Zahidul Islam Pranjol
European Journal of Obstetrics & Gynecology and Reproductive Biology.2020; 245: 121. CrossRef
Clinicopathologic Association and Prognostic Value of MELF Pattern in Invasive Endocervical Adenocarcinoma (ECA) as Classified by IECC
Sheila E. Segura, Lien Hoang, Monica Boros, Cristina Terinte, Anna Pesci, Sarit Aviel-Ronen, Takako Kiyokawa, Isabel Alvarado-Cabrero, Esther Oliva, Kay J. Park, Robert A. Soslow, Simona Stolnicu
International Journal of Gynecological Pathology.2020; 39(5): 436. CrossRef
Usual-Type Endocervical Adenocarcinoma with a Microcystic, Elongated, and Fragmented Pattern of Stromal Invasion: A Case Report with Emphasis on Ki-67 Immunostaining and Targeted Sequencing Results
Sangjoon Choi, Soohyun Hwang, Sung-Im Do, Hyun-Soo Kim
Case Reports in Oncology.2020; 13(3): 1421. CrossRef
High Expression of Galectin-1, VEGF and Increased Microvessel Density Are Associated with MELF Pattern in Stage I-III Endometrioid Endometrial Adenocarcinoma
Dmitry Aleksandrovich Zinovkin, Sergey Leonidovich Achinovich, Mikhail Grigoryevich Zubritskiy, Jacqueline Linda Whatmore, Md Zahidul Islam Pranjol
Journal of Pathology and Translational Medicine.2019; 53(5): 280. CrossRef
The Roles of Melf Patterns, the Depth of Invasion and Number of Tumor Emboli as the Predictive Factors of the Survival Rate Among Patients with Endometrioid Adenocarcinoma of the Corpus Uterus
D. A. Zinovkin
Health and Ecology Issues.2019; (1): 49. CrossRef
Non-endometrioid and high-grade endometrioid endometrial cancers show DNA fragmentation factor 40 (DFF40) and B-cell lymphoma 2 protein (BCL2) underexpression, which predicts disease-free and overall survival, but not DNA fragmentation factor 45 (DFF45) u
Tomasz Banas, Kazimierz Pitynski, Krzysztof Okon, Aleksandra Winiarska
BMC Cancer.2018;[Epub] CrossRef
Tumor-Associated T-Lymphocytes and Macrophages are Decreased in Endometrioid Endometrial Carcinoma with MELF-Pattern Stromal Changes
Dmitry Aleksandrovich Zinovkin, Md Zahidul Islam Pranjol, Il’ya Andreevich Bilsky, Valeriya Alexandrovna Zmushko
Cancer Microenvironment.2018; 11(2-3): 107. CrossRef
MELF pattern of myometrial invasion and role in possible endometrial cancer diagnostic pathway: A systematic review of the literature
Anastasia Prodromidou, George Vorgias, Konstantinos Bakogiannis, Nikolaos Kalinoglou, Christos Iavazzo
European Journal of Obstetrics & Gynecology and Reproductive Biology.2018; 230: 147. CrossRef
CORRELATIVE INTERRELATIONS OF THE TUMOR MICROENVIRONMENT AND RELATIVE RISK OF UNFAVOURABLE OUTCOME OF ENDOMETRIOID ADENOCARCINOMA OF THE CORPUS UTERI
D. A. Zinovkin
Health and Ecology Issues.2018; (3): 48. CrossRef

Prognostic Relevance of the Expression of CA IX, GLUT-1, and VEGF in Ovarian Epithelial Cancers: Kyungbin Kim, Won Young Park, Jee Yeon Kim, Mee Young Sol, Dong Hun Shin, Do Youn Park, Chang Hun Lee, Jeong Hee Lee, Kyung Un Choi; Korean J Pathol. 2012;46(6):532-540. Published online December 26, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.532

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Abstract PDF

Background

Tumor hypoxia is associated with malignant progression and treatment resistance. Hypoxia-related factors, such as carbonic anhydrase IX (CA IX), glucose transporter-1 (GLUT-1), and vascular endothelial growth factor (VEGF) permit tumor cell adaptation to hypoxia. We attempted to elucidate the correlation of these markers with variable clinicopathological factors and overall prognosis.

Methods

Immunohistochemistry for CA IX, GLUT-1, and VEGF was performed on formalin-fixed, paraffin-embedded tissues from 125 cases of ovarian epithelial cancer (OEC).

Results

CA IX expression was significantly associated with an endometrioid and mucinous histology, nuclear grade, tumor necrosis, and mitosis. GLUT-1 expression was associated with tumor necrosis and mitosis. VEGF expression was correlated only with disease recurrence. Expression of each marker was not significant in terms of overall survival in OECs; however, there was a significant correlation between poor overall survival rate and high coexpression of these markers.

Conclusions

The present study suggests that it is questionable whether CA IX, GLUT-1, or VEGF can be used alone as independent prognostic factors in OECs. Using at least two markers helps to predict patient outcomes in total OECs. Moreover, the inhibition of two target gene combinations might prove to be a novel anticancer therapy.

Citations

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Effect of Ultrasound Therapy at the ST11 on Sympathetic Nervous System Change: A Prospective Randomized Controlled Study
Shinwoo Kang, Dongho Keum
Journal of Korean Medicine Rehabilitation.2023; 33(4): 167. CrossRef
A systematic review verified by bioinformatic analysis based on TCGA reveals week prognosis power of CAIX in renal cancer
Zikuan Zhang, Bo Wu, Yuan Shao, Yongquan Chen, Dongwen Wang, Lucia Magnelli
PLOS ONE.2022; 17(12): e0278556. CrossRef
Effect of Acupuncture at the Field of the Auricular Branch of the Vagus Nerve on Autonomic Nervous System Change
Sunjoo An, Dongho Keum
Journal of Korean Medicine Rehabilitation.2021; 31(2): 81. CrossRef
Responses of Autonomic Nervous System and Gastrointestinal Function to Acupuncture at Abdominal Anterior Cutaneous Nerve : A Pilot Study
Seohyun Park, Hojun Kim, Dongho Keum
Journal of Korean Medicine.2019; 40(1): 99. CrossRef
Omega-3 polyunsaturated fatty acid docosahexaenoic acid and its role in exhaustive-exercise-induced changes in female rat ovulatory cycle
Abeer F. Mostafa, Shereen M. Samir, R.M. Nagib
Canadian Journal of Physiology and Pharmacology.2018; 96(4): 395. CrossRef
Clear cell carcinomas of the ovary and kidney: clarity through genomics
Jennifer X Ji, Yi Kan Wang, Dawn R Cochrane, David G Huntsman
The Journal of Pathology.2018; 244(5): 550. CrossRef
Prognostic Significance of Carbonic Anhydrase IX Expression in Cancer Patients: A Meta-Analysis
Simon J. A. van Kuijk, Ala Yaromina, Ruud Houben, Raymon Niemans, Philippe Lambin, Ludwig J. Dubois
Frontiers in Oncology.2016;[Epub] CrossRef
Review of Research Topics on Abdominal Examination
Jihye Kim, Jeong Hwan Park, Keun Ho Kim
Journal of Korean Medicine.2016; 37(3): 1. CrossRef
Expression of hypoxic markers and their prognostic significance in soft tissue sarcoma
JEUNG IL KIM, KYUNG UN CHOI, IN SOOK LEE, YOUNG JIN CHOI, WON TACK KIM, DONG HOON SHIN, KYUNGBIN KIM, JEONG HEE LEE, JEE YEON KIM, MEE YOUNG SOL
Oncology Letters.2015; 9(4): 1699. CrossRef
Evaluation of a Hypoxia Regulated Gene Panel in Ovarian Cancer
Amanda F. Baker, Scott W. Malm, Ritu Pandey, Cindy Laughren, Haiyan Cui, Denise Roe, Setsuko K. Chambers
Cancer Microenvironment.2015; 8(1): 45. CrossRef
Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells independently of their resistance to chemotherapy
MICHAL PASTOREK, VERONIKA SIMKO, MARTINA TAKACOVA, MONIKA BARATHOVA, MARIA BARTOSOVA, LUBA HUNAKOVA, OLGA SEDLAKOVA, SONA HUDECOVA, OLGA KRIZANOVA, FRANCK DEQUIEDT, SILVIA PASTOREKOVA, JAN SEDLAK
International Journal of Oncology.2015; 47(1): 51. CrossRef
Overexpression of Glucose Transporter-1 (GLUT-1) Predicts Poor Prognosis in Epithelial Ovarian Cancer
Hanbyoul Cho, You Sun Lee, Julie Kim, Joon-Yong Chung, Jae-Hoon Kim
Cancer Investigation.2013; 31(9): 607. CrossRef
Towards Lipidomics of Low-Abundant Species for Exploring Tumor Heterogeneity Guided by High-Resolution Mass Spectrometry Imaging
Jonathan Cimino, David Calligaris, Johann Far, Delphine Debois, Silvia Blacher, Nor Sounni, Agnès Noel, Edwin De Pauw
International Journal of Molecular Sciences.2013; 14(12): 24560. CrossRef

Vascular Endothelial Growth Factor Bioactivity and Its Receptors in Patients with Acute Respiratory Distress Syndrome.: Simona Gurzu, Ioan Jung, Leonard Azamfirei, Bong Young Shin, Raluca Solomon, Daria Demian, Judith Kovacs, Han Kyeom Kim; Korean J Pathol. 2011;45(2):139-145.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.139

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Abstract PDF

BACKGROUND
Pathogenesis of acute respiratory distress syndrome (ARDS) is a controversial issue. Few studies have analyzed the possible role of vascular endothelial growth factor (VEGF) and its receptors in this lesion.
METHODS
We compared the immunohistochemical expression of VEGF, its receptors (VEGFR1, VEGFR2) and CD68, in normal lungs and lungs with ARDS. Fifty necropsy cases and 12 lung biopsies with ARDS were analyzed. In total, eight cases were in the early stage and 54 cases were in late stage of ARDS. In addition, the serum level of VEGF165 was also determined.
RESULTS
In normal lungs, all antibodies marked the endothelial cells (EC) and pneumocytes (PC), except for CD68, which was expressed in the alveolar macrophages. In early ARDS, the intensity of VEGF165 and VEGFR2 decreased in both EC and PC. VEGF121 was absent in PC but its expression increased in bronchial epithelium. VEGFR1 was expressed in the integral PC. In late ARDS, VEGF165 down-regulation was more significant in PC and EC but its intensity increased in hyaline membranes (HM). In some cases, HM were CD68 positive. The serum level of VEGF165 was up-regulated, while VEGF165 intensity in PC decreased and the HM appeared in alveolar spaces.
CONCLUSIONS
Sporadic positivity of HM for CD68 and decreasing of VEGF165 expression in EC proved that VEGF165 is produced by PC, destroyed macrophages, and extravasated serum.

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Hallazgos similares al COVID-19 en un caso fatal de neumonía intersticial descamativa asociada con glomerulonefritis por IgA en una niña de 13 meses de edad
Simona Gurzu, Catalin-Bogdan Satala, Lorena Elena Melit, Adrian Streinu-Cercel, Dan Otelea, Brandusa Capalna, Claudiu Ioan Puiac, Janos Szederjesi, Ioan Jung
Kompass Neumología.2021; 3(2): 69. CrossRef
COVID-19 Like Findings in a Fatal Case of Idiopathic Desquamative Interstitial Pneumonia Associated With IgA Glomerulonephritis in a 13-Month-Old Child
Simona Gurzu, Catalin Bogdan Satala, Lorena Elena Melit, Adrian Streinu-Cercel, Dan Otelea, Brandusa Capalna, Claudiu Ioan Puiac, Janos Szederjesi, Ioan Jung
Frontiers in Pediatrics.2020;[Epub] CrossRef

Microvessel and Lymphatic Vessel Density and VEGFR-3 Expression of Papillary Thyroid Carcinoma with Comparative Analysis of Clinicopathological Characteristics.: Harin Cheong, Hanna Kang, Hyung Kyung Kim, Ji Yoon Bae, Dong Eun Song, Min Sun Cho, Sun Hee Sung, Woon Sup Han, Heasoo Koo; Korean J Pathol. 2010;44(3):243-251.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.243

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Abstract PDF

BACKGROUND
This study was done to see if there were correlations between anatomic and molecular parameters such as microvessel density (MVD), lymphatic vessel density (LVD), and vascular endothelial growth factor receptor (VEGFR)-3 expression and various clinical parameters for papillary thyroid carcinomas of size > 1.0 cm (PTCs) and size < or = 1.0 cm (papillary thyroid microcarcinomas, PTMCs). PTMCs were divided into two subgroups (0-5 mm and 6-10 mm).
METHODS
We analyzed 197 thyroid carcinomas including 113 PTCs and 84 PTMCs. Tissue samples form 30 patients from each group matched for clinical characteristics were selected for immunostaining.
RESULTS
Although PTCs and PTMCs showed significant differences in clinical characteristics, they did not show significant difference in MVD, LVD, or VEGFR-3 expression. There was a significantly higher LVD in the PTMC subgroup with the larger tumors but no difference in clinical characteristics. LVD was higher in patients > 45 years old (more apparent in the PTC group) and LVD had suggestive correlations with multicentricity and extrathyroidal extension depending on analytic conditions.
CONCLUSIONS
Since LVD showed variable correlations with clinical variables for papillary carcinoma of the thyroid depending on analytic conditions, the individually planned treatments based on overall clinicopathological factors are advised.

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Freeze-dried bovine amniotic membrane as a cell delivery scaffold in a porcine model of radiation-induced chronic wounds
Daemyung Oh, Daegu Son, Jinhee Kim, Sun-Young Kwon
Archives of Plastic Surgery.2021; 48(4): 448. CrossRef
Polydeoxyribonucleotide Improves Peripheral Tissue Oxygenation and Accelerates Angiogenesis in Diabetic Foot Ulcers
Seoyoung Kim, Junhyung Kim, Jaehoon Choi, Woonhyeok Jeong, Sunyoung Kwon
Archives of Plastic Surgery.2017; 44(06): 482. CrossRef

Expression of E-cadherin, Matrix Metalloproteinase, and Vascular Endothelial Growth Factor in Squamous Cell Carcinoma and Adenocarcinoma of the Lung.: Ji Sun Song, Mee Yon Cho, Kwang Hwa Park, Soon Hee Jung, Kwang Gil Lee; Korean J Pathol. 2000;34(12):972-981.

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Abstract PDF: E-cadherin is a calcium-dependent epithelial adhesion molecule which plays a role in the initial step of invasion of cancer cells. The step that follows the migration of separated tumor cells is a proteolytic lysis of basement membrane and extracellular matrix by protease of epithelial and endothelial cells such as matrix metalloproteinase (MMP). Vascular endothelial growth factor (VEGF) is known to be an endothelial cell-specific powerful mitogen as well as a vascular permeability factor. This study is aimed to evaluate the correlation between expression of these factors and pathologic or clinical variables and the roles and prognostic significance of those factors in squmous cell carcinoma and adenocarcinoma of the lung. Immunohistochemical stains were performed for E-cadherin, MMP-2, and VEGF in surgically resected specimens from 90 patients with squmous cell carcinoma and adenocarcinoma of the lung. Mean age of the patients was 59.7 years. Histologic type was categorized into 56 cases of squamous cell carcinoma and 34 cases of adenocarcinoma. Mean survival period of the 35 patients was 54 months. The immunohistochemical stains for E-cadherin, MMP-2, and VEGF revealed positive reaction in 67 cases (74.4%), 43 cases (47.8%), and 34 cases (37.8%), respectively. The expression of E-cadherin was higher in adenocarcinoma (82.4%) than in squamous cell carcinoma (69.6%). MMP-2 was expressed in the tumor cells, especially those invading into the surrounding stroma. The expression of MMP-2 was significantly correlated with the survival rate (p<0.05). The expression of VEGF in the tumor cells was significantly higher in cases with lymph node metastasis (p<0.05). In conclusion, these findings suggest that the expression of MMP-2 and VEGF predict poor prognosis of patients with squmous cell carcinoma and adenocarcinoma of the lung and that VEGF may play a role in tumor metastasis.

Expression of p53 and Vascular Endothelial Growth Factor mRNA in Angiogenesis of Non-Small Cell Lung Carcinoma.: Jun Seog Kim, Tae In Park, Myoung Hoon Lee, Eun Kyoung Kwak, Ji Young Park, Jung Sik Kwak, Jong Min Chae; Korean J Pathol. 2003;37(1):35-40.

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Abstract PDF: BACKGROUND
Angiogenesis is one of the most important factors in the progression and me-tastasis of malignancies. Angiogenesis is a multistep process requiring the interaction of numerous factors able to stimulate the growth and development of new vessels. But, understanding of the mechanism involved in VEGF expression is unclear.
METHODS
Expressions of p53 and VEGF, and neovasculiarization were examined in 19 cases of surgically resected non-small cell carcinoma of the lung by the immunohistochemical staining. Furthermore, VEGF mRNA expressions were quantified in all cases using the real-time quantitative RT-PCR. These results were compared with clinicopathologic parameters such as histologic grade and stage.
RESULTS
Tumors with high aberrant p53 expressions showed significantly higher VEGF mRNA ex-pressions and microvessel counts than those with low p53 expressions. Expressions of p53 as well as VEGF and micovessel counts were closely associated with the tumor stage, but not with the histologic grade and other clinical parameters.
CONCLUSIONS
These results suggest that aberrant p53 expression may play a role in the regulation of VEGF expression and may be involved in controlling angiogenesis in non-small cell carcinoma of the lung.

Expression of VEGF, MMP-9 and Neovascularization in Relationship to the Clinical Behavior of Giant Cell Tumors of Bone.: Kyung Hwa Lee, Jo Heon Kim, Min Keun Shim, Chang Woo Han, Sung Sun Kim, Sang Woo Juhng, Sung Taek Jung, Jae Hyuk Lee; Korean J Pathol. 2006;40(6):420-426.

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Abstract PDF: BACKGROUND
Giant cell tumors (GCT(s)) of bone are benign but can be locally aggressive neoplasms. Their clinical behavior has been difficult to predict on the basis of histology alone. This study investigated the neovascularization and expression of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase-9 (MMP-9) in GCT(s) of bone; in addition we evaluated their relationship to clinical behavior.
METHODS
We evaluated the microvessel number and density in 33 samples of giant cell tumor using CD34 immunohistochemistry. In addition, we examined the immunohistochemical expression of VEGF and MMP-9.
RESULTS
The microvessel number alone, not the microvessel density, had statistical association with the clinical stage of GCT(s) (p=0.045). The proportion of cases with strong expression of VEGF increased with advancing clinical stage, however, these results were not statistically significant (p=0.257). The percentage of the cases with strong expression of MMP-9 also increased with advancing clinical stage and this was statistically significant (p=0.022).
CONCLUSIONS
These results suggest that intratumor microvessel count and the expression of MMP-9 correlate with GCT stage. Evaluation of their expression may therefore provide prognostic information on the aggressive behavior of GCT(s) of bone.

Expression of Vascular Endothelial Growth Factors A,C and D in Gastric Adenocarcinoma.: Myoung Ja Chung, Jin Wook Lee, Ki Hoon Yu, Doo Hyun Yang, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee; Korean J Pathol. 2005;39(2):99-105.

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Abstract PDF: BACKGROUND
Vascular endothelial growth factor (VEGF)-C and VEGF-D are novel growth factors that regulate lymphatic vessel growth. This study was designed to examine whether the expression of three VEGF family members, VEGF-A, VEGF-C and VEGF-D are associated with the clinicopathologic parameters, especially with lymph node metastasis, in advanced gastric carcinomas.
METHODS
Immunohistochemical staining was performed for VEGF-A, VEGF-C, and VEGF-D in the surgically resected specimens from 102 patients with advanced gastric carcinoma. The mRNA expressions of the three VEGF family members were assessed in 16 cases of tumor tissues and their corresponding non-neoplastic tissues.
RESULTS
Of the 102 gastric carcinomas, 74 (73%), 82 (80%), and 34 (33%) cases showed cytoplasmic immunoreactivity for VEGF-A, VEGF-C and VEGF-D, respectively. Both VEGF-A and VEGF-C expressions were associated with lymphatic invasion and lymph node metastasis (p<0.05), but the VEGF-D expression was not associated with them (p>0.05). In the tumor tissue, VEGF-C mRNA expression was greater, while VEGF-D mRNA expression was lower than in the nonneoplatic tissue adjacent to the tumor.
CONCLUSIONS
VEGF-A and VEGF-C may play important roles for the lymphatic spread of gastric carcinoma. We suggest that neutralizing both VEGF-A and VEGF-C may be reguired to block lymph node metastasis.

The Relationship between PTEN Tumor Suppressor Gene and Vascular Endothelial Growth Factor-Mediated Angiogenesis in Breast Cancer.: Jean Kyung Park, Min Jung Jung, Bong Kwon Chun, Bang Hur; Korean J Pathol. 2004;38(2):100-105.

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Abstract PDF: BACKGROUND
PTEN is a novel tumor suppressor gene located at chromosome 10q23.3. Loss of PTEN function has been implicated in the progression of several types of cancer. Angiogenesis is a critical factor in tumor growth and metastasis. We investigated PTEN expression in invasive breast cancers and described its role in the regulation of angiogenesis related to vascular endothelial growth factor (VEGF).
METHODS
Forty-five, surgically resected, formalin-fixed and paraffin embedded breast cancer tissue samples were analyzed for PTEN and VEGF expressions by immunohistochemistry and for microvessel density (MVD) by CD34 immunostaining.
RESULTS
Loss of PTEN expression was found in 35.6% (16/45) of the breast cancer tissues, all of which showed positive VEGF expression. Among 29 cases with normal PTEN expression, 15 (51.7%) were VEGF positive. MVD was significantly higher in tumors with a loss of PTEN expression than in those with normal PTEN expression.
CONCLUSION
A loss of PTEN expression might increase the VEGF-related angiogenesis in breast cancer. There was no correlation between PTEN expression and clinicopathologic parameters. Detection of the loss of PTEN expression may serve as a useful biologic marker for progression in invasive breast cancer.

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