Journal of Pathology and Translational Medicine

Original Article

Prognostic significance of viable tumor size measurement in hepatocellular carcinomas after preoperative locoregional treatment: Yoon Jung Hwang, Youngeun Lee, Hyunjin Park, Yangkyu Lee, Kyoungbun Lee, Haeryoung Kim; J Pathol Transl Med. 2021;55(5):338-348. Published online September 2, 2021; DOI: https://doi.org/10.4132/jptm.2021.07.26

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Background
Preoperative locoregional treatment (LRT) for hepatocellular carcinoma (HCC) often induces intratumoral necrosis without affecting the overall tumor size, and residual viable tumor size (VTS) on imaging is an important clinical parameter for assessing post-treatment response. However, for surgical specimens, it is unclear whether the VTS would be more relevant to prognosis compared to total tumor size (TTS).
Methods
A total of 142 surgically resected solitary HCC cases were retrospectively reviewed. The TTS and VTS were assessed by applying the modified Response Evaluation Criteria in Solid Tumors method to the resected specimens, and correlated with the clinicopathological features and survival.
Results
As applying VTS, 13/142 cases (9.2%) were down-staged to ypT1a. Although the survival analysis results for overall survival according to TTS or VTS were similar, VTS was superior to predict disease-free survival (DFS; p = .023) compared to TTS (p = .08). In addition, multivariate analysis demonstrated VTS > 2 cm to be an independent predictive factor for decreased DFS (p = .001). In the subpopulation of patients with LRT (n = 54), DFS in HCCs with TTS or VTS > 2 cm were significantly shorter than those with TTS or VTS ≤ 2 cm (p = .047 and p = .001, respectively). Interestingly, HCCs with TTS > 2 cm but down-staged to VTS ≤ 2 cm after preoperative LRT had similar survival to those with TTS ≤ 2 cm.
Conclusions
Although the prognostic impact of tumor size was similar regardless of whether TTS or VTS was applied, reporting VTS may help to increase the number of candidates for surgery in HCC patients with preoperative LRT.

Citations

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Measures for response assessment in HCC treatment
Fereshteh Yazdanpanah, Omar Al-Daoud, Moein Moradpour, Stephen Hunt
Hepatoma Research.2024;[Epub] CrossRef
Machine Learning for Dynamic Prognostication of Patients With Hepatocellular Carcinoma Using Time-Series Data: Survival Path Versus Dynamic-DeepHit HCC Model
Lujun Shen, Yiquan Jiang, Tao Zhang, Fei Cao, Liangru Ke, Chen Li, Gulijiayina Nuerhashi, Wang Li, Peihong Wu, Chaofeng Li, Qi Zeng, Weijun Fan
Cancer Informatics.2024;[Epub] CrossRef
Construction and validation of a novel signature based on epithelial-mesenchymal transition–related genes to predict prognosis and immunotherapy response in hepatocellular carcinoma by comprehensive analysis of the tumor microenvironment
Biao Gao, Yafei Wang, Shichun Lu
Functional & Integrative Genomics.2023;[Epub] CrossRef
Cellular senescence affects energy metabolism, immune infiltration and immunotherapeutic response in hepatocellular carcinoma
Biao Gao, Yafei Wang, Shichun Lu
Scientific Reports.2023;[Epub] CrossRef

Review

Hepatocellular adenomas: recent updates: Haeryoung Kim, Young Nyun Park; J Pathol Transl Med. 2021;55(3):171-180. Published online April 7, 2021; DOI: https://doi.org/10.4132/jptm.2021.02.27

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Abstract PDF

Hepatocellular adenoma (HCA) is a heterogeneous entity, from both the histomorphological and molecular aspects, and the resultant subclassification has brought a strong translational impact for both pathologists and clinicians. In this review, we provide an overview of the recent updates on HCA from the pathologists’ perspective and discuss several practical issues and pitfalls that may be useful for diagnostic practice.

Citations

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Prognostic role of selection criteria for liver transplantation in patients with hepatocellular carcinoma: Review and bibliometric
Pamela Scarlett Espinoza Loyola, Diana Laura Muratalla Bautista, Karen Adela Hernández Bautista, Elizabeth Gil White, José Antonio González Moreno, Daniel Angel Torres del Real, Víctor Manuel Páez Zayas, Carla Escorza-Molina, Fernando Mondragón Rodríguez,
iLIVER.2024; 3(1): 100077. CrossRef
ACG Clinical Guideline: Focal Liver Lesions
Catherine Frenette, Mishal Mendiratta-Lala, Reena Salgia, Robert J. Wong, Bryan G. Sauer, Anjana Pillai
American Journal of Gastroenterology.2024; 119(7): 1235. CrossRef
Hepatocellular adenoma update: diagnosis, molecular classification, and clinical course
Sarah Poetter-Lang, Ahmed Ba-Ssalamah, Nina Bastati, Sami A Ba-Ssalamah, Jacqueline C Hodge, Giuseppe Brancatelli, Valérie Paradis, Valérie Vilgrain
British Journal of Radiology.2024; 97(1163): 1740. CrossRef
Fatal rupture of hepatic adenomatosis: Autopsy case and review of the literature
Sarra Ben Abderrahim, Khouloud Chérif, Zeineb Nfikha, Sarra Gharsallaoui, Imen El Aini, Maher Jedidi, Moncef Mokni, Mohamed Ben Dhiab
Journal of Forensic Sciences.2023; 68(4): 1393. CrossRef
Large Hepatocellular Adenoma Presenting with Iron Deficiency Anemia: A Case Report
Young Kwon Koh, Su Hyun Yoon, Sung Han Kang, Hyery Kim, Ho Joon Im, Suhyeon Ha, Jung-Man Namgoong, Kyung-Nam Koh
Clinical Pediatric Hematology-Oncology.2023; 30(1): 25. CrossRef
A Case Report on a Giant Hepatic Inflammatory Adenoma in a Young Female That Presented as Spontaneous Intrahepatic Hematoma
Andreas Kyvetos, Panagiota Voukelatou, Ioannis Vrettos, Spyridon Pantzios , Ioannis Elefsiniotis
Cureus.2023;[Epub] CrossRef
Advances in Histological and Molecular Classification of Hepatocellular Carcinoma
Joon Hyuk Choi, Swan N. Thung
Biomedicines.2023; 11(9): 2582. CrossRef
Estrobolome and Hepatocellular Adenomas—Connecting the Dots of the Gut Microbial β-Glucuronidase Pathway as a Metabolic Link
Sandica Bucurica, Mihaela Lupanciuc, Florentina Ionita-Radu, Ion Stefan, Alice Elena Munteanu, Daniela Anghel, Mariana Jinga, Elena Laura Gaman
International Journal of Molecular Sciences.2023; 24(22): 16034. CrossRef
Hepatocellular adenoma: what we know, what we do not know, and why it matters
Paulette Bioulac‐Sage, Annette S H Gouw, Charles Balabaud, Christine Sempoux
Histopathology.2022; 80(6): 878. CrossRef

Original Articles

Guanabenz Acetate Induces Endoplasmic Reticulum Stress–Related Cell Death in Hepatocellular Carcinoma Cells: Hyo Jeong Kang, Hyang Sook Seol, Sang Eun Lee, Young-Ah Suh, Jihun Kim, Se Jin Jang, Eunsil Yu; J Pathol Transl Med. 2019;53(2):94-103. Published online January 16, 2019; DOI: https://doi.org/10.4132/jptm.2019.01.14

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Abstract PDF Supplementary Material

Background
Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients.
Methods
Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 drugs from the Prestwick Chemical Library. The efficacy and mechanisms of action of the candidate anti-cancer drug were analyzed via cell viability, cell cycle assays, and western blotting.
Results
Guanabenz acetate, which has been used as an antihypertensive drug, was screened as a candidate anti-cancer agent for HCC through a drug sensitivity assay by using the primary cultured HCC cells and HCC cell lines. Guanabenz acetate reduced HCC cell viability through apoptosis and autophagy. This occurred via inhibition of growth arrest and DNA damage-inducible protein 34, increased phosphorylation of eukaryotic initiation factor 2α, increased activating transcription factor 4, and cell cycle arrest.
Conclusions
Guanabenz acetate induces endoplasmic reticulum stress–related cell death in HCC and may be repositioned as an anti-cancer therapeutic agent for HCC patients.

Citations

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Current trends and future prospects of drug repositioning in gastrointestinal oncology
Nayeralsadat Fatemi, Mina Karimpour, Hoda Bahrami, Mohammad Reza Zali, Vahid Chaleshi, Andrea Riccio, Ehsan Nazemalhosseini-Mojarad, Mehdi Totonchi
Frontiers in Pharmacology.2024;[Epub] CrossRef
ER stress signaling at the interphase between MASH and HCC
Younis Hazari, Eric Chevet, Béatrice Bailly-Maitre, Claudio Hetz
Hepatology.2024;[Epub] CrossRef
Small molecules for impairing endoplasmic reticulum in cancer
Tripti Mishra, Navneet Dubey, Sudipta Basu
Organic & Biomolecular Chemistry.2024; 22(44): 8689. CrossRef
Guanabenz acetate, an antihypertensive drug repurposed as an inhibitor of Escherichia coli biofilm
Arakkaveettil Kabeer Farha, Olivier Habimana, Harold Corke, Olaya Rendueles
Microbiology Spectrum.2024;[Epub] CrossRef
The integrated stress response in cancer progression: a force for plasticity and resistance
Caleb L. Lines, Morgan J. McGrath, Tanis Dorwart, Crystal S. Conn
Frontiers in Oncology.2023;[Epub] CrossRef
Endoplasmic reticulum stress: Multiple regulatory roles in hepatocellular carcinoma
Jiacheng Wu, Shan Qiao, Yien Xiang, Menying Cui, Xiaoxiao Yao, Ruixin Lin, Xuewen Zhang
Biomedicine & Pharmacotherapy.2021; 142: 112005. CrossRef
The two faces of the Integrated Stress Response in cancer progression and therapeutic strategies
Eugenia Licari, Luis Sánchez-del-Campo, Paola Falletta
The International Journal of Biochemistry & Cell Biology.2021; 139: 106059. CrossRef
Repurposing of Guanabenz acetate by encapsulation into long-circulating nanopolymersomes for treatment of triple-negative breast cancer
Yusuf A. Haggag, Mohamed Yasser, Murtaza M. Tambuwala, Suleiman S. El Tokhy, Mohammad Isreb, Ahmed A. Donia
International Journal of Pharmaceutics.2021; 600: 120532. CrossRef
Endoplasmic reticulum stress: New insights into the pathogenesis and treatment of retinal degenerative diseases
Marina S. Gorbatyuk, Christopher R. Starr, Oleg S. Gorbatyuk
Progress in Retinal and Eye Research.2020; 79: 100860. CrossRef
Delineating the role of eIF2α in retinal degeneration
Christopher R. Starr, Marina S. Gorbatyuk
Cell Death & Disease.2019;[Epub] CrossRef
Repositioning of Guanabenz in Conjugation with Gold and Silver Nanoparticles against Pathogenic Amoebae Acanthamoeba castellanii and Naegleria fowleri
Areeba Anwar, Mohammad Ridwane Mungroo, Ayaz Anwar, William J. Sullivan, Naveed Ahmed Khan, Ruqaiyyah Siddiqui
ACS Infectious Diseases.2019; 5(12): 2039. CrossRef

C-reactive Protein Overexpression in the Background Liver of Hepatitis B Virus–Associated Hepatocellular Carcinoma Is a Prognostic Biomarker: Jin Ho Shin, Eunsil Yu, Eun Na Kim, Chong Jai Kim; J Pathol Transl Med. 2018;52(5):267-274. Published online July 27, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.14

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Abstract PDF

Background
Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). Peripheral blood C-reactive protein (CRP) concentration and CRP overexpression in HCC cells are proven to be prognostic markers for HCC, but the significance of CRP expression in non-neoplastic hepatocytes, which are the primary origin of CRP, has not been studied. This study was conducted to determine the clinicopathologic significance of CRP immunoreactivity in the background liver of HBV-associated HCC.
Methods
CRP immunostaining was done on tissue microarrays of non-neoplastic liver tissues obtained from surgically resected, treatment-naïve HBV-associated HCCs (n = 156). The relationship between CRP immunoreactivity and other clinicopathologic parameters including cancer-specific survival was analyzed. CRP immunoreactivity was determined using a 4-tier grading system: grades 0, 1, 2, and 3.
Results
CRP was positive in 139 of 156 cases (89.1%) of non-neoplastic liver in patients with HCCs: grade 1 in 83 cases (53.2%); grade 2 in 50 cases (32.1%); and grade 3 in six cases (3.8%). The patients with diffuse CRP immunoreactivity (grade 3) had decreased cancer-specific survival (p = .031) and a tendency for shorter interval before early recurrence (p = .050). The degree of CRP immunoreactivity correlated with serum CRP concentration (p < .001).
Conclusions
CRP immunoreactivity in non-neoplastic liver is a novel biomarker for poor cancer-specific survival of HBV-associated HCC and correlates with serum CRP concentration.

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Analysis of Inflammatory and Thyroid Hormone Levels Based on Hepatitis A and B Virus Immunity Status: Age and Sex Stratification
Hyeokjun Yun, Jae-Sik Jeon, Jae Kyung Kim
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Ferritin and procalcitonin serve as discriminative inflammatory biomarkers and can predict the prognosis of severe fever with thrombocytopenia syndrome in its early stages
Keping Chen, Huidi Sun, Yu Geng, Chuankun Yang, Chun Shan, Yuxin Chen
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Evaluation of Serum Ferritin, Procalcitonin, and C-Reactive Protein for the Prediction of Severity and Mortality in Hemorrhagic Fever With Renal Syndrome
Lihe Che, Zedong Wang, Na Du, Liang Li, Yinghua Zhao, Kaiyu Zhang, Quan Liu
Frontiers in Microbiology.2022;[Epub] CrossRef
Hepatocellular adenomas: recent updates
Haeryoung Kim, Young Nyun Park
Journal of Pathology and Translational Medicine.2021; 55(3): 171. CrossRef
A prospective follow-up study of the relationship between high-sensitivity C-reactive protein and primary liver cancer
Sarah Tan Siyin, Tong Liu, Wenqiang Li, Nan Yao, Guoshuai Xu, Jun Qu, Yajun Chen
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CRP Levels in Viral Hepatitis: A Meta-Analysis Study
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Case Studies

Combined Hepatocellular Carcinoma and Neuroendocrine Carcinoma with Ectopic Secretion of Parathyroid Hormone: A Case Report and Review of the Literature: Hyun Jung Kwon, Ji-Won Kim, Haeryoung Kim, YoungRok Choi, Soomin Ahn; J Pathol Transl Med. 2018;52(4):232-237. Published online May 25, 2018; DOI: https://doi.org/10.4132/jptm.2018.05.17

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Abstract PDF

Primary combined hepatocellular carcinoma (HCC) and neuroendocrine carcinoma is a rare entity, and so is hypercalcemia due to ectopic parathyroid hormone (PTH) secretion by tumor. A 44-year old man with hepatitis B virus associated chronic liver disease presented with a hepatic mass. Hemihepatectomy discovered the mass as combined HCC and poorly differentiated cholangiocarcinoma. During adjuvant chemoradiation therapy, he presented with nausea, and multiple systemic metastases were found. Laboratory tests revealed hypercalcemia with markedly elevated PTH and neuron specific enolase. Parathyroid scan showed normal uptake in parathyroid glands, suggestive of ectopic PTH secretion. Subsequently, immunohistochemistry of neuroendocrine marker was performed on the primary lesion, and confirmed the neuroendocrine differentiation in non-HCC component. The patient died 71 days after surgery. This report may suggest the possibility of ectopic PTH secretion by neuroendocrine carcinoma of hepatic origin causing hypercalcemia. Caution for neuroendocrine differentiation should be exercised when diagnosing poorly differentiated HCC.

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Case report: mixed large-cell neuroendocrine and hepatocellular carcinoma of the liver
Xin Gao, Heng Wang, Zheyu Niu, Meng Liu, Xiaohan Kong, Hongrui Sun, Chaoqun Ma, Huaqiang Zhu, Jun Lu, Xu Zhou
Frontiers in Oncology.2024;[Epub] CrossRef
Mixed glandular neuroendocrine carcinoma of the endometrium with hypercalcemic crisis
Mei Luo, Xiaoxia Yu, Zhongpei Chen, Zhenhan Li
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Mixed Primary Hepatocellular Carcinoma and Hepatic Neuroendocrine Carcinoma: Case Report and Literature Review
Woo Young Shin, Keon Young Lee, Kyeong Deok Kim
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Comparison of Metastatic Patterns Among Neuroendocrine Tumors, Neuroendocrine Carcinomas, and Nonneuroendocrine Carcinomas of Various Primary Organs
Hyung Kyu Park, Ghee Young Kwon
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Immunohistochemical characterization of a steroid-secreting oncocytic adrenal carcinoma responsible for paraneoplastic hyperparathyroidism
Magalie Haissaguerre, Estelle Louiset, Christofer C Juhlin, Adam Stenman, Christophe Laurent, Hélène Trouette, Hervé Lefebvre, Antoine Tabarin
European Journal of Endocrinology.2023; 188(4): K11. CrossRef
Neuroendocrine neoplasms of the biliary tree, liver and pancreas: a pathological approach
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Contrast-Enhanced Ultrasound Findings of Hepatocellular Carcinoma With Neuroendocrine Carcinoma: A Case Report
Hong Wang, Dan Yang, Zhenru Wu, Yan Luo, Wenwu Ling
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Combined primary hepatic neuroendocrine carcinoma and hepatocellular carcinoma: case report and literature review
Akira Nakano, Kenichi Hirabayashi, Hiroshi Yamamuro, Taro Mashiko, Yoshihito Masuoka, Seiichiro Yamamoto, Soji Ozawa, Toshio Nakagohri
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Filomena Cetani, Elena Pardi, Claudio Marcocci
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Chikara Ebisutani, Seitetsu Yoon, Toshiki Hyodo, Takafumi Watanabe, Hirofumi Okada, Yutaka Shirakawa, Yoshio Sakamoto, Shigeya Hirohata
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Two-in-one: A pooled analysis of primary hepatic neuroendocrine carcinoma combined/collided with hepatocellular carcinoma
Jia-Xi Mao, Fei Teng, Ke-Yan Sun, Cong Liu, Guo-Shan Ding, Wen-Yuan Guo
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Primary hepatic neuroendocrine carcinoma coexisting with distal cholangiocarcinoma
Qi Xin, Rong Lv, Cheng Lou, Zhe Ma, Gui-Qiu Liu, Qin Zhang, Hai-Bo Yu, Chuan-Shan Zhang
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Nusrat Jahan, Irfan Warraich, Edwin Onkendi, Sanjay Awasthi
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Hepatocellular Carcinoma Arising in a Huge Hepatocellular Adenoma with Bone Marrow Metaplasia: Hyo Jeong Kang, Hui Jeong Jeong, So-Woon Kim, Eunsil Yu, Young-Joo Lee, So Yeon Kim, Jihun Kim; J Pathol Transl Med. 2018;52(4):226-231. Published online December 27, 2017; DOI: https://doi.org/10.4132/jptm.2017.11.12

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Abstract PDF

Hepatocellular adenoma (HCA) is the most common type of benign liver tumor, and its major complication is malignant transformation to hepatocellular carcinoma (HCC). Here, we report a case of HCC arising in HCA with bone marrow metaplasia in a 24-year-old Korean woman who presented with abdominal discomfort. A huge liver mass was found on abdominal ultrasonography. She underwent surgical hepatic resection, and the resected specimen was entirely involved by a 20-cm-sized tumor. Histological review revealed a well differentiated HCC arising from inflammatory HCA with β-catenin nuclear positivity and bone marrow metaplasia that contained hematopoietic cells. This case was unique because malignant transformation, inflammatory type HCA, β-catenin nuclear staining, and bone marrow metaplasia were simultaneously observed. Additionally, it should be noted that a large HCA with β-catenin activation can undergo malignant transformation and should be surgically resected in a timely manner.

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Adult Hepatocellular Carcinoma Coexisting with Extramedullary Hematopoiesis
Hirotsugu Noguchi, Michiyo Higashi, Ryo Desaki, Takashi Tasaki, Mari Kirishima, Ikumi Kitazono, Kazuhiro Tabata, Akihide Tanimoto
International Journal of Surgical Pathology.2022; 30(3): 339. CrossRef
Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice
Wenhua Shao, Orgil Jargalsaikhan, Mayuko Ichimura-Shimizu, Qinyi Cai, Hirohisa Ogawa, Yuko Miyakami, Kengo Atsumi, Mitsuru Tomita, Mitsuko Sutoh, Shunji Toyohara, Ryoji Hokao, Yasusei Kudo, Takeshi Oya, Koichi Tsuneyama
International Journal of Molecular Sciences.2022; 23(19): 11923. CrossRef
Bilateral Diffuse Nodular Pulmonary Ossification Mimicking Metastatic Disease in a Patient with Fibrolamellar Hepatocellular Carcinoma
Pattamon Sutthatarn, Cara E. Morin, Jessica Gartrell, Wayne L. Furman, Max R. Langham, Teresa Santiago, Andrew J. Murphy
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Malignant transformation of liver fatty acid binding protein-deficient hepatocellular adenomas: histopathologic spectrum of a rare phenomenon
Juan Putra, Linda D. Ferrell, Annette S.H. Gouw, Valerie Paradis, Arvind Rishi, Christine Sempoux, Charles Balabaud, Swan N. Thung, Paulette Bioulac-Sage
Modern Pathology.2020; 33(4): 665. CrossRef
Hepatocellular carcinoma arising from hepatic adenoma in a young woman
Haythem Yacoub, Hela Kchir, Dhouha Cherif, Hajer Hassine, Slim Haouet, Asma Ayari, Habiba Mizouni, Saber Mannai, Mohamed Tahar Khalfallah, Nadia Maamouri
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Metanephric adenoma with osseous metaplasia and bone marrow elements
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Original Articles

The Clinicopathological and Prognostic Significance of the Gross Classification of Hepatocellular Carcinoma: Yangkyu Lee, Hyunjin Park, Hyejung Lee, Jai Young Cho, Yoo-Seok Yoon, Young-Rok Choi, Ho-Seong Han, Eun Sun Jang, Jin-Wook Kim, Sook-Hyang Jeong, Soomin Ahn, Haeryoung Kim; J Pathol Transl Med. 2018;52(2):85-92. Published online November 24, 2017; DOI: https://doi.org/10.4132/jptm.2017.11.13

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Abstract PDF

Background
We aimed to determine the clinicopathological significance of the gross classification of hepatocellular carcinoma (HCC) according to the Korean Liver Cancer Association (KLCA) guidelines.
Methods
A retrospective analysis was performed on 242 cases of consecutively resected solitary primary HCC between 2003 and 2012 at Seoul National University Bundang Hospital. The gross classification (vaguely nodular [VN], expanding nodular [EN], multinodular confluent [MC], nodular with perinodular extension [NP], and infiltrative [INF]) was reviewed for all cases, and were correlated with various clinicopathological features and the expression status of “stemness”-related (cytokeratin 19 [CK19], epithelial cell adhesion molecule [EpCAM]), and epithelial-mesenchymal transition (EMT)–related (urokinase plasminogen activator receptor [uPAR] and Ezrin) markers.
Results
Significant differences were seen in overall survival (p=.015) and disease-free survival (p = .034) according to the gross classification; INF type showed the worst prognosis while VN and EN types were more favorable. When the gross types were simplified into two groups, type 2 HCCs (MC/NP/INF) were more frequently larger and poorly differentiated, and showed more frequent microvascular and portal venous invasion, intratumoral fibrous stroma and higher pT stages compared to type 1 HCCs (EN/VN) (p<.05, all). CK19, EpCAM, uPAR, and ezrin expression was more frequently seen in type 2 HCCs (p<.05, all). Gross classification was an independent predictor of both overall and disease-free survival by multivariate analysis (overall survival: p=.030; hazard ratio, 4.118; 95% confidence interval, 1.142 to 14.844; disease-free survival: p=.016; hazard ratio, 1.617; 95% confidence interval, 1.092 to 2.394).
Conclusions
The gross classification of HCC had significant prognostic value and type 2 HCCs were associated with clinicopathological features of aggressive behavior, increased expression of “stemness”- and EMT-related markers, and decreased survival.

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European Journal of Gastroenterology & Hepatology.2023; 35(4): 431. CrossRef
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Salvatore Lorenzo Renne, Samantha Sarcognato, Diana Sacchi, Maria Guido, Massimo Roncalli, Luigi Terracciano, Luca Di Tommaso
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Prognostic significance of viable tumor size measurement in hepatocellular carcinomas after preoperative locoregional treatment
Yoon Jung Hwang, Youngeun Lee, Hyunjin Park, Yangkyu Lee, Kyoungbun Lee, Haeryoung Kim
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Prognosis of Hepatocellular Carcinoma after Liver Transplantation: Comparative Analysis with Partial Hepatectomy: Kyuho Lee, Kyoung-Bun Lee, Nam-Joon Yi, Kyung-Suk Suh, Ja-June Jang; J Pathol Transl Med. 2017;51(1):79-86. Published online December 25, 2016; DOI: https://doi.org/10.4132/jptm.2016.10.13

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Background
Liver transplantation (LT) is the treatment of choice for hepatocellular carcinoma (HCC). The aim of this study was to investigate the recurrence rate of HCC after LT and prognostic factors for recurrence by comparing LT with non-transplanted resection. Methods: The participants were 338 patients who underwent LT between 1996 and 2012 at Seoul National University Hospital (LT group) and 520 HCC patients who underwent partial hepatectomy between 1995 and 2006 (control group, non-LT group). Results: In the LT group, 68 of 338 patients (19.8%) showed relapse, and the recurrence rate was lower than that in the non-LT group (64.9%, 357/520, p < .001). Stratification analysis by American Joint Committee on Cancer (AJCC) stage showed that the stage I-II LT group had a lower recurrence rate than the non-LT group. Univariate comparative analysis demonstrated that multiplicity of tumor, tumor size, gross type, Edmondson- Steiner (ES) nuclear grade, extent of tumor, angioinvasion, AJCC stage, Milan criteria, University of California at San Francisco criteria on explant pathology (all p < .001), positive expression of cytokeratin 19 (p = .002), and preoperative α-fetoprotein (AFP) (p < .001) were predictors of tumor recurrence. In multivariate analysis, LT, preoperative AFP, multiplicity of tumor, extent of tumor, size of tumor, and ES nuclear grade were independent prognostic factors. Conclusions: LT might have a protective effect against the late recurrence of stage I-II HCC compared to non-LT, and the prognostic factors for recurrence were similar to previously well-known prognostic factors for HCC.

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SIRT7, H3K18ac, and ELK4 Immunohistochemical Expression in Hepatocellular Carcinoma: Hye Seung Lee, Wonkyung Jung, Eunjung Lee, Hyeyoon Chang, Jin Hyuk Choi, Han Gyeom Kim, Aeree Kim, Baek-hui Kim; J Pathol Transl Med. 2016;50(5):337-344. Published online August 5, 2016; DOI: https://doi.org/10.4132/jptm.2016.05.20

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Abstract PDF

Background
SIRT7 is one of the histone deacetylases and is NAD-dependent. It forms a complex with ETS-like transcription factor 4 (ELK4), which deacetylates H3K18ac and works as a transcriptional suppressor. Overexpression of SIRT7 and deacetylation of H3K18ac have been shown to be associated with aggressive clinical behavior in some cancers, including hepatocellular carcinoma (HCC). The present study investigated the immunohistochemical expression of SIRT7, H3K18ac, and ELK4 in hepatocellular carcinoma.
Methods
A total of 278 HCC patients were enrolled in this study. Tissue microarray blocks were made from existing paraffin-embedded blocks. Immunohistochemical expressions of SIRT7, H3K18ac and ELK4 were scored and analyzed.
Results
High SIRT7 (p = .034), high H3K18ac (p = .001), and low ELK4 (p = .021) groups were associated with poor outcomes. Age < 65 years (p = .028), tumor size ≥ 5 cm (p = .001), presence of vascular emboli (p = .003), involvement of surgical margin (p = .001), and high American Joint Committee on Cancer stage (III&V) (p < .001) were correlated with worse prognoses. In multivariate analysis, H3K18ac (p = .001) and ELK4 (p = .015) were the significant independent prognostic factors.
Conclusions
High SIRT7 expression with poor overall survival implies that deacetylation of H3K18ac contributes to progression of HCC. High H3K18ac expression with poor prognosis is predicted due to a compensation mechanism. In addition, high ELK4 expression with good prognosis suggests another role of ELK4 as a tumor suppressor beyond SIRT7’s helper. In conclusion, we could assume that the H3K18ac deacetylation pathway is influenced by many other factors.

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Oncotarget.2017; 8(44): 77309. CrossRef

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

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Abstract 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.

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Immunohistochemical Expression and Clinical Significance of Suggested Stem Cell Markers in Hepatocellular Carcinoma: Jong Jin Sung, Sang Jae Noh, Jun Sang Bae, Ho Sung Park, Kyu Yun Jang, Myoung Ja Chung, Woo Sung Moon; J Pathol Transl Med. 2016;50(1):52-57. Published online November 18, 2015; DOI: https://doi.org/10.4132/jptm.2015.10.09

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Abstract PDF

Background
Increasing evidence has shown that tumor initiation and growth are nourished by a small subpopulation of cancer stem cells (CSCs) within the tumor mass. CSCs are posited to be responsible for tumor maintenance, growth, distant metastasis, and relapse after curative operation. We examined the expression of CSC markers in paraffin-embedded tissue sections of hepatocellular carcinoma (HCC) and correlated the results with clinicopathologic characteristics. Methods: Immunohistochemical staining for the markers believed to be expressed in the CSCs, including epithelial cell adhesion molecule (EpCAM), keratin 19 (K19), CD133, and CD56, was performed in 82 HCC specimens. Results: EpCAM expression was observed in 56% of the HCCs (46/82) and K19 in 6% (5/82). EpCAM expression in HCC significantly correlated with elevated α-fetoprotein level, microvessel invasion of tumor cells, and high histologic grade. In addition, Ep- CAM expression significantly correlated with K19 expression. The overall survival and relapsefree survival rates in patients with EpCAM-expressing HCC were relatively lower than those in patients with EpCAM-negative HCC. All but two of the 82 HCCs were negative for CD133 and CD56, respectively. Conclusions: Our results suggest that HCCs expressing EpCAM are associated with unfavorable prognostic factors and have a more aggressive clinical course than those not expressing EpCAM. Further, the expression of either CD133 or CD56 in paraffin-embedded HCC tissues appears to be rare.

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Caecilia Sukowati, Loraine Kay D. Cabral, Beatrice Anfuso, Francesco Dituri, Roberto Negro, Gianluigi Giannelli, Claudio Tiribelli
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Aiat Shaban Hemida, Doha Maher Taie, Moshira Mohamed Abd El-Wahed, Mohammed Ibrahim Shabaan, Mona Saeed Tantawy, Nermine Ahmed Ehsan
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Asmaa G. Abdou, Nanis S. Holah, Dina S. Elazab, Walaa G. El-Gendy, Mohammed T. Badr, Dalia R. Al-Sharaky
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SALL4 Expression in Hepatocellular Carcinomas Is Associated with EpCAM-Positivity and a Poor Prognosis: Hyunjin Park, Hyejung Lee, An Na Seo, Jai Young Cho, Young Rok Choi, Yoo-Seok Yoon, Ho-Seong Han, Young Nyun Park, Haeryoung Kim; J Pathol Transl Med. 2015;49(5):373-381. Published online August 10, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.09

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Abstract PDF

Background
There is increasing interest in hepatocellular carcinomas (HCC) expressing “stemness”-related markers, as they have been associated with aggressive behavior and poor prognosis. In this study, we investigated the usefulness of Sal-like protein 4 (SALL4), a recently proposed candidate marker of “stemness.” Methods: Immunohistochemical stains were performed for SALL4, K19, and epithelial cellular adhesion molecule (EpCAM) on tissue microarrays constructed from 190 surgically resected HCCs, and the results were correlated with the clinicopathological features and patient survival data. Results: Nuclear SALL4 expression was observed in 39/190 HCCs (20.5%), while K19 and EpCAM were expressed in 30 (15.9%) and 92 (48.7%) HCCs, respectively. The nuclear expression was generally weak, punctate or clumped. SALL4 expression was significantly associated with a poor overall survival compared to SALL4-negative HCCs (p = .014) compared to SALL4-negative HCCs. On multivariate analysis adjusted for tumor size, multiplicity, vascular invasion, and pathological tumor stage, SALL4 remained as a significant independent predictor of decreased overall survival (p= .004). SALL4 expression was positively correlated with EpCAM expression (p = .013) but not with K19 expression. HCCs that expressed both SALL4 and EpCAM were associated with significantly decreased overall survival, compared to those cases which were negative for both of these markers (p = .031). Conclusions: Although SALL4 expression was not significantly correlated with other clinicopathological parameters suggestive of tumor aggressiveness, SALL4 expression was an independent predictor of poor overall survival in human HCCs, and was also positively correlated with EpCAM expression.

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Oncogene.2017; 36(17): 2435. CrossRef
Higher expression of SALL4 predicts poor cancer prognosis: A meta-analysis
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Oncotarget.2017; 8(14): 22968. CrossRef
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International Journal of Molecular Medicine.2016; 38(5): 1587. CrossRef
Oncogenic protein SALL4 and ZNF217 as prognostic indicators in solid cancers: a meta-analysis of individual studies
Ji Cheng, Jinbo Gao, Xiaoming Shuai, Kaixiong Tao
Oncotarget.2016; 7(17): 24314. CrossRef

Review

Pathology-MRI Correlation of Hepatocarcinogenesis: Recent Update: Jimi Huh, Kyung Won Kim, Jihun Kim, Eunsil Yu; J Pathol Transl Med. 2015;49(3):218-229. Published online May 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.04.15

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Abstract PDF

Understanding the important alterations during hepatocarcinogenesis as well as the characteristic magnetic resonance imaging (MRI) and histopathological features will be helpful for managing patients with chronic liver disease and hepatocellular carcinoma. Recent advances in MRI techniques, such as fat/iron quantification, diffusion-weighted images, and gadoxetic acid-enhanced MRI, have greatly enhanced our understanding of hepatocarcinogenesis.

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Journal of Gastrointestinal Cancer.2018; 49(3): 302. CrossRef

Original Article

Overexpression of C-reactive Protein as a Poor Prognostic Marker of Resectable Hepatocellular Carcinomas: Jin Ho Shin, Chong Jai Kim, Eun Jeong Jeon, Chang Ohk Sung, Hwa Jeong Shin, Jene Choi, Eunsil Yu; J Pathol Transl Med. 2015;49(2):105-111. Published online March 12, 2015; DOI: https://doi.org/10.4132/jptm.2015.01.19

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Abstract PDF

Background
C-reactive protein (CRP) is an acute phase reactant synthesized in the liver. CRP immunoreactivity is a feature of inflammatory hepatocellular adenomas with a higher risk of malignant transformation. A high serum CRP level denotes poor prognosis in hepatocellular carcinoma (HCC) patients. This study was conducted to determine whether CRP is produced in HCC and to assess the clinicopathologic significance of CRP expression in cancer cells. Methods: CRP immunoreactivity was examined in treatment-naïve HCCs (n=224) using tissue microarrays and was correlated with clinicopathologic parameters. The expression of CRP mRNA and protein was also assessed in 12 HCC cases by quantitative real-time polymerase chain reaction and immunoblotting. Hep3B and SNU-449 HCC cell lines were used for the analysis of CRP mRNA regulation by interleukin 6 (IL-6). Results: CRP was expressed in 133 of 224 HCCs (59.4%) with a variable degree of immunoreactivity (grade 1 in 25.9%; grade 2 in 20.1%; grade 3 in 13.4%). There was an inverse relationship between grade 3 CRP immunoreactivity and cancer-specific survival (p=.0047), while no associations were found with other parameters, including recurrence-free survival. The CRP mRNA expression level was significantly higher in CRP immunopositive cases than in immunonegative cases (p<.05). CRP mRNA expression was increased in Hep3B cells, but was not detected in SNU-449 cells even after IL-6 treatment. Conclusions: We report the expression of CRP in HCC for the first time. CRP expression was associated with poor cancer-specific survival in patients with resectable HCC.

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The quest for precision oncology with immune checkpoint inhibitors for hepatocellular carcinoma
Giuseppe Cabibbo, Amit G. Singal
Journal of Hepatology.2022; 76(2): 262. CrossRef
HNF-1β is a More Sensitive and Specific Marker Than C-Reactive Protein for Identifying Biliary Differentiation in Primary Hepatic Carcinomas
Pallavi A. Patil, Tamar Taddei, Dhanpat Jain, Xuchen Zhang
Archives of Pathology & Laboratory Medicine.2022; 146(2): 220. CrossRef
Malignant transformation of hepatocellular adenoma
Céline Julien, Brigitte Le Bail, Laurence Chiche, Charles Balabaud, Paulette Bioulac-Sage
JHEP Reports.2022; 4(3): 100430. CrossRef
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Cardiovascular Therapeutics.2022; 2022: 1. CrossRef
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American Journal of Surgical Pathology.2021; 45(9): 1252. CrossRef
Cytochrome P450 4A11 expression in tumor cells: A favorable prognostic factor for hepatocellular carcinoma patients
Hyuk Soo Eun, Sang Yeon Cho, Byung Seok Lee, Sup Kim, In‐Sang Song, Kwangsik Chun, Cheong‐Hae Oh, Min‐Kyung Yeo, Seok Hyun Kim, Kyung‐Hee Kim
Journal of Gastroenterology and Hepatology.2019; 34(1): 224. CrossRef
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Yoon Ah Cho, Ji Myung Chung, Hyunmi Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
Cancer Research and Treatment.2019; 51(3): 1052. CrossRef
Increased systemic zonula occludens 1 associated with inflammation and independent biomarker in patients with hepatocellular carcinoma
Amit Kumar Ram, Biju Pottakat, Balasubramaniyan Vairappan
BMC Cancer.2018;[Epub] CrossRef
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Jin Ho Shin, Eunsil Yu, Eun Na Kim, Chong Jai Kim
Journal of Pathology and Translational Medicine.2018; 52(5): 267. CrossRef
Efficacy of vasopressin V2 receptor antagonist tolvaptan in treatment of hepatic edema
Yasunari Hiramine, Hirofumi Uto, Yasushi Imamura, Takuya Hiwaki, Takeshi Kure, Sho Ijuin, Kohei Oda, Seiichi Mawatari, Kotaro Kumagai, Koki Tokunaga, Hirofumi Higashi, Ichiro Kanetsuki, Osamu Kubozono, Shigeho Maenohara, Akio Ido
Hepatology Research.2017; 47(6): 542. CrossRef
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Oncotarget.2017; 8(29): 47090. CrossRef
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International Journal of Clinical Oncology.2016; 21(2): 373. CrossRef
Current Proceedings in the Molecular Dissection of Hepatocellular Adenomas: Review and Hands-on Guide for Diagnosis
Diane Goltz, Hans-Peter Fischer
International Journal of Molecular Sciences.2015; 16(9): 20994. CrossRef

Brief Case Report

Periductal Stromal Tumor of Breast: A Case Report and A Review of Literature: Salma L. Abbasi, Kate McNamara, Mohammed S. Absar, Alison Darlington, Francene Clucas, Sami Titi; Korean J Pathol. 2014;48(6):442-444. Published online December 31, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.6.442

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