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Original Article
Nuclear Expression of Hepatitis B Virus X Protein Is Associated with Recurrence of Early-Stage Hepatocellular Carcinomas: Role of Viral Protein in Tumor Recurrence
Jing Jin, Hae Yoen Jung, KyuHo Lee, Nam-Joon Yi, Kyung-Suk Suh, Ja-June Jang, Kyoung-Bun Lee
J Pathol Transl Med. 2016;50(3):181-189.   Published online April 17, 2016
DOI: https://doi.org/10.4132/jptm.2016.03.18
  • 17,703 View
  • 102 Download
  • 9 Web of Science
  • 7 Crossref
AbstractAbstract PDF
Background
Hepatitis B virus (HBV) plays well-known roles in tumorigenesis of hepatocellular carcinoma (HCC) in infected patients. However, HBV-associated protein status in tumor tissues and the relevance to tumor behavior has not been reported. Our study aimed to examine the expression of HBV-associated proteins in HCC and adjacent nontumorous tissue and their clinicopathologic implication in HCC patients.
Methods
HBV surface antigen (HBsAg), HBV core antigen (HBcAg), and HBV X protein (HBx) were assessed in 328 HBV-associated HCCs and in 155 matched nontumorous tissues by immunohistochemistry staining.
Results
The positive rates of HBsAg and cytoplasmic HBx staining in tumor tissue were lower than those in nontumorous tissue (7.3% vs. 57.4%, p < .001; 43.4% vs. 81.3%, p < .001). Conversely, nuclear HBx was detected more frequently in tumors than in nontumorous tissue (52.1% vs. 30.3%, p < .001). HCCs expressing HBsAg, HBcAg, or cytoplasmic HBx had smaller size; lower Edmondson-Steiner (ES) nuclear grade, pT stage, and serum alpha-fetoprotein, and less angioinvasion than HCCs not expressing HBV-associated proteins. Exceptionally, nuclear HBx-positive HCCs showed higher ES nuclear grade and more frequent large-vessel invasion than did nuclear HBx-negative HCCs. In survival analysis, only nuclear HBx-positive HCCs had shorter disease-free survival than nuclear HBx-negative HCCs in pT1 and ES nuclear grade 1–2 HCC subgroup (median, 126 months vs. 35 months; p = .015).
Conclusions
Our data confirmed that expression of normal HBV-associated proteins generally decreases in tumor cells in comparison to nontumorous hepatocytes, with the exception of nuclear HBx, which suggests that nuclear HBx plays a role in recurrence of well-differentiated and early-stage HCCs.

Citations

Citations to this article as recorded by  
  • Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis
    Anja Schollmeier, Mirco Glitscher, Eberhard Hildt
    International Journal of Molecular Sciences.2023; 24(5): 4964.     CrossRef
  • Nomogram to predict the prognosis of patients with AFP-negative hepatocellular carcinoma undergoing chemotherapy: A SEER based study
    Lei Wang, Jin-Lin Peng, Ji-Zhou Wu
    Medicine.2023; 102(13): e33319.     CrossRef
  • Tertiary Prevention of HCC in Chronic Hepatitis B or C Infected Patients
    Wei Teng, Yen-Chun Liu, Wen-Juei Jeng, Chien-Wei Su
    Cancers.2021; 13(7): 1729.     CrossRef
  • Suppression of hepatitis b virus by a combined activity of CRISPR/Cas9 and HBx proteins
    S. A. Brezgin, A. P. Kostyusheva, V. N. Simirsky, E. V. Volchkova, D. S. Chistyakov, D. S. Kostyushev, V. P. Chulanov
    Russian Journal of Infection and Immunity.2019; 9(3-4): 476.     CrossRef
  • Hepatitis B virus surface gene pre‐S2 mutant as a high‐risk serum marker for hepatoma recurrence after curative hepatic resection
    Chia‐Jui Yen, Yu‐Lin Ai, Hung‐Wen Tsai, Shih‐Huang Chan, Chia‐Sheng Yen, Kuang‐Hsiung Cheng, Yun‐Ping Lee, Chia‐Wei Kao, Yu‐Chun Wang, Yi‐Lin Chen, Cheng‐Han Lin, Tsunglin Liu, Huey‐Pin Tsai, Jen‐Ren Wang, Ih‐Jen Su, Wenya Huang
    Hepatology.2018; 68(3): 815.     CrossRef
  • Integrin α6 as an invasiveness marker for hepatitis B viral X-driven hepatocellular carcinoma
    Yi Rang Kim, Mi Ran Byun, Jin Woo Choi
    Cancer Biomarkers.2018; 23(1): 135.     CrossRef
  • Clinical Implications of Hepatitis B Virus RNA and Covalently Closed Circular DNA in Monitoring Patients with Chronic Hepatitis B Today with a Gaze into the Future: The Field Is Unprepared for a Sterilizing Cure
    Anastasiya Kostyusheva, Dmitry Kostyushev, Sergey Brezgin, Elena Volchkova, Vladimir Chulanov
    Genes.2018; 9(10): 483.     CrossRef
Case Studies
Mediastinal Glomus Tumor: A Case Report and Literature Review
Si-Hyong Jang, Hyun Deuk Cho, Ji-Hye Lee, Hyun Ju Lee, Hae Yoen Jung, Kyung-Ju Kim, Sung Sik Cho, Mee-Hye Oh
J Pathol Transl Med. 2015;49(6):520-524.   Published online August 4, 2015
DOI: https://doi.org/10.4132/jptm.2015.07.02
  • 9,999 View
  • 71 Download
  • 11 Web of Science
  • 11 Crossref
AbstractAbstract PDF
A glomus tumor in the mediastinum is very uncommon, and only five cases have been reported in the English literature. We recently encountered a 21-year-old woman with an asymptomatic mediastinal mass that measured 5.3 × 4.0 cm. Surgical excision was performed, and the tumor was finally diagnosed as mediastinal glomus tumor with an uncertain malignant potential. After reviewing this case and previous reports, we analyzed the clinicopathologic features associated with progression of such a tumor.

Citations

Citations to this article as recorded by  
  • Primary glomus tumor of the thymus in a 66-year-old patient
    Yibing Zang, Ruixing Zhao, Chengquan Ma, Dejun Gao
    Journal of Cardiothoracic Surgery.2024;[Epub]     CrossRef
  • A case of mediastinal mesenchymal tumor with pericytic neoplasm feature that responded to radiation therapy
    Miho Muramoto, Shintaro Kanda, Takashi Kobayashi, Hisashi Tamada, Ayumu Fukazawa, Keiichirou Koiwai, Tomonobu Koizumi
    Thoracic Cancer.2023; 14(13): 1204.     CrossRef
  • Report of a vagal paraganglioma at the cervicothoracic junction
    Jun Yun, Danielle Kapustin, Aisosa Omorogbe, Samuel J. Rubin, Daniel G. Nicastri, Reade A. De Leacy, Azita Khorsandi, Mark L. Urken
    Head & Neck.2023;[Epub]     CrossRef
  • Total-Body Irradiation Is Associated With Increased Incidence of Mesenchymal Neoplasia in a Radiation Late Effects Cohort of Rhesus Macaques (Macaca mulatta)
    W. Shane Sills, Janet A. Tooze, John D. Olson, David L. Caudell, Greg O. Dugan, Brendan J. Johnson, Nancy D. Kock, Rachel N. Andrews, George W. Schaaf, Richard A. Lang, J. Mark Cline
    International Journal of Radiation Oncology*Biology*Physics.2022; 113(3): 661.     CrossRef
  • Mesenchymal Tumors of the Mediastinum: An Update on Diagnostic Approach
    Joon Hyuk Choi, Jae Y. Ro
    Advances in Anatomic Pathology.2021; 28(5): 351.     CrossRef
  • La glomangiomatose médiastinale postérieure : localisation exceptionnelle d’une tumeur rare. À propos d’un cas
    A. Machboua, S. Hamraoui, S. Zarouki, I. Kamaoui, I. Alloubi
    Revue des Maladies Respiratoires.2021; 38(8): 848.     CrossRef
  • An unusual case of chest wall glomus tumor presenting with axillary pain: a case report and literature review
    Leila Oryadi Zanjani, Bahman Shafiee Nia, Farzad Vosoughi, Elham Mirzaian, Leila Aghaghazvini, Aidin Arabzadeh
    European Journal of Medical Research.2021;[Epub]     CrossRef
  • Clinical Implications of 18F-FDG PET/CT in Malignant Glomus Tumors of the Esophagus
    Romain-David Seban, Laurence Bozec, Laurence Champion
    Clinical Nuclear Medicine.2020; 45(6): e301.     CrossRef
  • Symplastic glomus tumor of the urinary bladder treated by robot-assisted partial cystectomy: a case report and literature review
    Franco Palmisano, Franco Gadda, Matteo G. Spinelli, Marco Maggioni, Bernardo Rocco, Emanuele Montanari
    Urologia Journal.2018; 85(3): 130.     CrossRef
  • Thoracoscopic Surgery for Glomus Tumor: An Uncommon Mediastinal Neoplasm and Iatrogenic Tracheal Rupture
    Zhongjie Fang, Dehua Ma, Baofu Chen, Huarong Luo
    Case Reports in Surgery.2017; 2017: 1.     CrossRef
  • Asymptomatic Glomus Tumor of the Mediastinum
    Meletios Kanakis, Nikoletta Rapti, Maria Chorti, Achilleas Lioulias
    Case Reports in Surgery.2015; 2015: 1.     CrossRef
A Rare Case of Primary Tubular Adenocarcinoma of the Thymus, Enteric Immunophenotype: A Case Study and Review of the Literature
Hae Yoen Jung, Hyundeuk Cho, Jin-Haeng Chung, Sang Byoung Bae, Ji-Hye Lee, Hyun Ju Lee, Si-Hyong Jang, Mee-Hye Oh
J Pathol Transl Med. 2015;49(4):331-334.   Published online June 1, 2015
DOI: https://doi.org/10.4132/jptm.2015.04.16
  • 8,952 View
  • 82 Download
  • 10 Web of Science
  • 12 Crossref
AbstractAbstract PDF
Thymic carcinomas are uncommon malignant tumors, and thymic adenocarcinomas are extremely rare. Here, we describe a case of primary thymic adenocarcinoma in a 59-year-old woman. Histological examination of the tumor revealed tubular morphology with expression of cytokeratin 20 and caudal-type homeobox 2 according to immunohistochemistry, suggesting enteric features. Extensive clinical and radiological studies excluded the possibility of an extrathymic primary tumor. A review of the literature revealed only two global cases of primary tubular adenocarcinomas of the thymus with enteric immunophenotype.

Citations

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  • Clinical characteristics and prognosis of primary thymic adenocarcinoma: A single‐center retrospective analysis
    Qian Hong, Rui Han, Chen Chen, Fuquan Wang, Sining Zhang, Chenguang Zhao, Fang Li, Juwei Mu, Jiagen Li
    Thoracic Cancer.2024; 15(24): 1815.     CrossRef
  • Case report: Primary adenocarcinoma NOS of the thymus and cytological features
    Jonathan Willner, Osvaldo Hernandez, Lea Azour, Andre L. Moreira
    Diagnostic Cytopathology.2023;[Epub]     CrossRef
  • Enteric-type thymic adenocarcinoma: a case report and literature review focusing on prognosis based on histological subtypes
    Rurika Hamanaka, Kei Nakano, Takaaki Tsuboi, Kazuhito Hatanaka, Mitsutomo Kohno, Ryota Masuda, Masayuki Iwazaki
    General Thoracic and Cardiovascular Surgery.2022; 70(5): 501.     CrossRef
  • Metastatic thymic-enteric adenocarcinoma responding to chemoradiation plus anti-angiogenic therapy: A case report
    Man Li, Xiao-Yu Pu, Li-Hua Dong, Peng-Yu Chang
    World Journal of Clinical Cases.2021; 9(7): 1676.     CrossRef
  • A case report: primary thymic adenocarcinoma with enteric differentiation
    Yuuki Kou, Hirokazu Tanaka, Nobuhisa Yamazaki, Hiroyoshi Watanabe, Makoto Sonobe
    The Journal of the Japanese Association for Chest Surgery.2020; 34(2): 107.     CrossRef
  • Thymic enteric type adenocarcinoma: A case report with cytological features
    Marie Tamai, Mitsuaki Ishida, Yusuke Ebisu, Hisashi Okamoto, Chika Miyasaka, Chisato Ohe, Yoshiko Uemura, Tomohito Saito, Tomohiro Murakawa, Koji Tsuta
    Diagnostic Cytopathology.2018; 46(1): 92.     CrossRef
  • Histologic characteristics of thymic adenocarcinomas: Clinicopathologic study of a nine-case series and a review of the literature
    Ah-Young Kwon, Joungho Han, Jinah Chu, Yong Soo Choi, Byeong-Ho Jeong, Myung-Ju Ahn, Yong Chan Ahn
    Pathology - Research and Practice.2017; 213(2): 106.     CrossRef
  • Characterization of genetic aberrations in a single case of metastatic thymic adenocarcinoma
    Yeonghun Lee, Sehhoon Park, Se-Hoon Lee, Hyunju Lee
    BMC Cancer.2017;[Epub]     CrossRef
  • Cytologic Characteristics of Thymic Adenocarcinoma with Enteric Differentiation: A Study of Four Fine-Needle Aspiration Specimens
    Ah-Young Kwon, Joungho Han, Hae-yon Cho, Seokhwi Kim, Heejin Bang, Jiyeon Hyeon
    Journal of Pathology and Translational Medicine.2017; 51(5): 509.     CrossRef
  • Mucinous cystic tumor with CK20 and CDX2 expression of the thymus: Is this a benign counterpart of adenocarcinoma of the thymus, enteric type?
    Jun Akiba, Hiroshi Harada, Shintaro Yokoyama, Toshihiro Hashiguchi, Akihiko Kawahara, Masahiro Mitsuoka, Shinzo Takamori, Hirohisa Yano
    Pathology International.2016; 66(1): 29.     CrossRef
  • Colon cancer chemotherapy for a patient with CDX2-expressing metastatic thymic adenocarcinoma: a case report and literature review
    Akihiko Sawaki, Mikiya Ishihara, Yuji Kozuka, Hiroyasu Oda, Satoshi Tamaru, Yumiko Sugawara, Yoshiki Yamashita, Toshiro Mizuno, Taizo Shiraishi, Naoyuki Katayama
    International Cancer Conference Journal.2016; 5(2): 113.     CrossRef
  • Metastatic Thymic Adenocarcinoma from Colorectal Cancer
    Mina Lee, Suk Jin Choi, Yong Han Yoon, Joung-Taek Kim, Wan Ki Baek, Young Sam Kim
    The Korean Journal of Thoracic and Cardiovascular Surgery.2015; 48(6): 447.     CrossRef
Original Articles
The Histologic Cut-off Point for Adjacent and Remote Non-neoplastic Liver Parenchyma of Hepatocellular Carcinoma in Chronic Hepatitis B Patients
Hae Yoen Jung, Soo Hee Kim, Jin Jing, Jae Moon Gwak, Chul Ju Han, Ja-June Jang, Kyoung-Bun Lee
Korean J Pathol. 2012;46(4):349-358.   Published online August 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.349
  • 7,084 View
  • 51 Download
  • 6 Crossref
AbstractAbstract PDF
Background

The molecular profile of peritumoral non-neoplastic liver parenchyma (PNLP) has recently been suggested as predictive factor of early and late recurrence of hepatocellular carcinoma (HCC). However, there is no definite cut-off point for tumor-free PNLP in terms of either histological or molecular changes. Therefore, our aim is to determine the numerical cut-off point for separating adjacent PNLP and remote PNLP in histopathologic perspective.

Methods

Peritumoral tissues from 20 resected HCC patients were sampled from 0 to 40 mm distance from the tumor border (divided into 5-mm columns). Histopathologic parameters such as necroinflammatory activity, fibrosis, bile ductular reaction, hepatic venulitis, peliosis, and steatosis were compared between each column.

Results

The morphologic changes just adjacent to the tumor were notably severe and faded with distance. The parenchyma within 10 mm of the tumor showed significantly severe inflammation, fibrosis, peliosis and hepatic venulitis compared with those from farther areas. The histopathologic changes of the parenchyma became stable beyond 20 mm.

Conclusions

Results of this study revealed that the parenchyma within 10 mm distance from the tumor, or adjacent PNLP, has histopathologic changes that are directly affected by the tumor, and the parenchyma beyond 20 mm as the remote PNLP without tumor effect.

Citations

Citations to this article as recorded by  
  • Peritumoral histopathologic findings in patients with chronic viral hepatitis‐associated hepatocellular carcinoma
    Burcin Pehlivanoglu, Anil Aysal, Cihan Agalar, Tufan Egeli, Mucahit Ozbilgin, Tarkan Unek, Tugba Unek, Ilhan Oztop, Ozgul Sagol
    APMIS.2022; 130(6): 346.     CrossRef
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    Ting-Ting Zhang, Si-Si Ye, Jun Liang, Li Bai
    Experimental Biology and Medicine.2020; 245(8): 703.     CrossRef
  • Evaluation of Peritumoral Fibrosis in Metastatic Colorectal Adenocarcinoma to the Liver Using Digital Image Analysis
    Kevin M Waters, Tricia R Cottrell, Sepideh Besharati, Qingfeng Zhu, Robert A Anders
    American Journal of Clinical Pathology.2019; 151(2): 226.     CrossRef
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    BioMed Research International.2018; 2018: 1.     CrossRef
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    Korean Journal of Pathology.2013; 47(6): 557.     CrossRef
Cyclooxygenase-2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma
Ji Won Lee, Jeong Hwan Park, Ja Hee Suh, Kyung Han Nam, Ji-Young Choe, Hae Yoen Jung, Ji Yoen Chae, Kyung Chul Moon
Korean J Pathol. 2012;46(3):237-245.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.237
  • 7,736 View
  • 48 Download
  • 16 Crossref
AbstractAbstract PDF
Background

The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines.

Methods

Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines.

Results

Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity.

Conclusions

This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.

Citations

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