Journal of Pathology and Translational Medicine

Original Articles

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.

Citations

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Related Factors of Hepatocellular Carcinoma Recurrence Associated With Hyperglycemia After Liver Transplantation
Yujian Zheng, Qing Cai, Lishan Peng, Shibo Sun, Shaoping Wang, Jie Zhou
Transplantation Proceedings.2021; 53(1): 177. CrossRef
Oncological Outcomes of Hepatic Resection vs Transplantation for Localized Hepatocellular Carcinoma
A.T. Akcam, A.G. Saritas, A. Ulku, A. Rencuzogullari
Transplantation Proceedings.2019; 51(4): 1147. CrossRef
Clustering Asian Countries According to the Trend of liver cancer Mortality Rates: an Application of Growth Mixture Models
Maryam Salari, Anoshirvan Kazemnejad, Farid Zayeri
Iranian Red Crescent Medical Journal.2017;[Epub] 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.

Citations

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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

Clinicopathological Analysis of Hepatocellular Adenoma According to New Bordeaux Classification: Report of Eight Korean Cases: Hyunchul Kim, Ja-June Jang, Dong-Sik Kim, Beom Woo Yeom, Nam Hee Won; Korean J Pathol. 2013;47(5):411-417. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.411

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Abstract PDF

Background

Hepatocellular adenoma (HCA) is a rare benign tumor of the liver. A subtype classification of HCA (hepatocyte nuclear factor 1α [HNF1α]-mutated, β-catenin-mutated HCA, inflammatory HCA, and unclassified HCA) has recently been established based on a single institutional review of a HCA series by the Bordeaux group.

Methods

We used histologic and immunohistochemical parameters to classify and evaluate eight cases from our institution. We evaluated the new classification method and analyzed correlations between our results and those of other reports.

Results

Seven of our eight cases showed histologic and immunohistochemical results consistent with previous reports. However, one case showed overlapping histologic features, as previously described by the Bordeaux group. Four cases showed glutamine synthetase immunohistochemical staining inconsistent with their classification, indicating that glutamine synthetase staining may not be diagnostic for β-catenin-mutated HCA. HNF1α-mutated HCA may be indicated by the absence of liver fatty acid binding protein expression. Detection of amyloid A may indicate inflammatory HCA. HCA with no mutation in the HNF1α or β-catenin genes and no inflammatory protein expression is categorized as unclassified HCA.

Conclusions

Although the new classification is now generally accepted, validation through follow-up studies is necessary.

Citations

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Relevance of morphological features for hepatocellular adenoma classification in pathology practice
Carla Henriques Agostini, Osmar Damasceno Ribeiro, Arlete Fernandes, Adriana Caroli-Bottino, Vera Lucia Pannain
Surgical and Experimental Pathology.2020;[Epub] CrossRef
The molecular functions of hepatocyte nuclear factors – In and beyond the liver
Hwee Hui Lau, Natasha Hui Jin Ng, Larry Sai Weng Loo, Joanita Binte Jasmen, Adrian Kee Keong Teo
Journal of Hepatology.2018; 68(5): 1033. CrossRef
Hepatocellular adenoma: Classification, variants and clinical relevance
Paulette Bioulac-Sage, Christine Sempoux, Charles Balabaud
Seminars in Diagnostic Pathology.2017; 34(2): 112. CrossRef
A Limited Immunohistochemical Panel Can Subtype Hepatocellular Adenomas for Routine Practice
Brent K. Larson, Maha Guindi
American Journal of Clinical Pathology.2017; 147(6): 557. CrossRef
Hepatocellular Neoplasms Arising in Association With Androgen Use
Sounak Gupta, Bita V. Naini, Richard Munoz, Rondell P. Graham, Benjamin R. Kipp, Michael S. Torbenson, Taofic Mounajjed
American Journal of Surgical Pathology.2016; 40(4): 454. CrossRef
Pigmented hepatocellular adenomas have a high risk of atypia and malignancy
Taofic Mounajjed, Saba Yasir, Patrice A Aleff, Michael S Torbenson
Modern Pathology.2015; 28(9): 1265. CrossRef

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

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51 Download
6 Crossref

Abstract 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

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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
Prognostic value of non-invasive fibrosis indices post-curative resection in hepatitis-B-associated hepatocellular carcinoma patients
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
Fibrosis-4 Model Influences Results of Patients with Hepatocellular Carcinoma Undergoing Hepatectomy
Haiqing Wang, Aixiang Liu, Wentao Bo, Xielin Feng, Yong Hu, Lang Tian, Hui Zhang, Xiaoli Tang, Lixia Zhang
BioMed Research International.2018; 2018: 1. CrossRef
Forns index predicts recurrence and death in patients with hepatitis B‐related hepatocellular carcinoma after curative resection
Won‐Mook Choi, Jeong‐Hoon Lee, Hongkeun Ahn, Hyeki Cho, Young Youn Cho, Minjong Lee, Jeong‐ju Yoo, Yuri Cho, Dong Hyeon Lee, Yun Bin Lee, Eun Ju Cho, Su Jong Yu, Nam‐Joon Yi, Kwang‐Woong Lee, Yoon Jun Kim, Jung‐Hwan Yoon, Kyung‐Suk Suh, Chung Yong Kim, Hy
Liver International.2015; 35(8): 1992. CrossRef
Renal Histologic Parameters Influencing Postoperative Renal Function in Renal Cell Carcinoma Patients
Myoung Ju Koh, Beom Jin Lim, Kyu Hun Choi, Yon Hee Kim, Hyeon Joo Jeong
Korean Journal of Pathology.2013; 47(6): 557. CrossRef

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