Journal of Liver Cancer

Original Article

The dual role of transforming growth factor-beta signatures in human B viral multistep hepatocarcinogenesis: early and late responsive genes: Jeong Eun Yoo, Ji Hae Nahm, Young-Joo Kim, Youngsic Jeon, Young Nyun Park; J Liver Cancer. 2022;22(2):115-124. Published online May 20, 2022; DOI: https://doi.org/10.17998/jlc.2022.04.20

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Background/Aim
Transforming growth factor-beta (TGF-β) has a dichotomous role, functioning as a tumor suppressor and tumor promoter. TGF-β signatures, explored in mouse hepatocytes, have been reported to predict the clinical outcomes of hepatocellular carcinoma (HCC) patients; HCCs exhibiting early TGF-β signatures showed a better prognosis than those with late TGF-β signatures. The expression status of early and late TGF-β signatures remains unclear in defined lesions of human B-viral multistep hepatocarcinogenesis.
Methods
The expression of TGF-β signatures, early and late responsive signatures of TGF-β were investigated and analyzed for their correlation in cirrhosis, low-grade dysplastic nodules (DNs), high-grade DNs, early HCCs and progressed HCCs (pHCCs) by real-time PCR and immunohistochemistry.
Results
The expression levels of TGF-β signaling genes (TGFB1, TGFBR1, TGFBR2 and SMAD4) gradually increased with the progression of hepatocarcinogenesis, peaking in pHCCs. The expression of early responsive genes of TGF-β (GADD45B, FBP1, CYP1A2 and CYP3A4) gradually decreased, and that of the late TGF-β signatures (TWIST and SNAI1) significantly increased according to the progression of multistep hepatocarcinogenesis. Furthermore, mRNA levels of TWIST and SNAI1 were well correlated with those of stemness markers, with upregulation of TGF-β signaling, whereas FBP1 expression was inversely correlated with that of stemness markers.
Conclusions
The enrichment of the late responsive signatures of TGF-β with induction of stemness is considered to be involved in the progression of the late stage of multistep hepatocarcinogenesis, whereas the early responsive signatures of TGF-β are suggested to have tumor-suppressive roles in precancerous lesions of the early stage of multistep hepatocarcinogenesis.

Citations

Citations to this article as recorded by

Structure, unique biological properties, and mechanisms of action of transforming growth factor β
Nataliya Zelisko, Roman Lesyk, Rostyslav Stoika
Bioorganic Chemistry.2024; 150: 107611. CrossRef
TGFβ in Pancreas and Colorectal Cancer: Opportunities to Overcome Therapeutic Resistance
Allan M. Johansen, Steven D. Forsythe, Callum T. McGrath, Grayson Barker, Hugo Jimenez, Ravi K. Paluri, Boris C. Pasche
Clinical Cancer Research.2024; 30(17): 3676. CrossRef
Identification of potential biomarkers for lung adenocarcinoma: a study based on bioinformatics analysis combined with validation experiments
Chuchu Zhang, Ying Liu, Yingdong Lu, Zehui Chen, Yi Liu, Qiyuan Mao, Shengchuan Bao, Ge Zhang, Ying Zhang, Hongsheng Lin, Haiyan Li
Frontiers in Oncology.2024;[Epub] CrossRef

Case Report

A Case of Lymphocyte-Rich Hepatocellular Carcinoma in a Patient Who Was Treated for Colon Cancer: Jae Won Song, Ho Soo Chun, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Young Nyun Park, Dai Hoon Han, Do Young Kim; J Liver Cancer. 2021;21(1):69-75. Published online March 31, 2021; DOI: https://doi.org/10.17998/jlc.21.1.69

4,236 Views
91 Downloads
2 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) primarily originates in the liver with hepatic differentiation. However, HCCs are not homogenous, and approximately 35% of HCC cases are classified as histopathological variants that present distinct pathologic characteristics. In particular, the lymphocyte-rich variant is the rarest subtype accounting for less than 1% of HCCs, which is not well known to date about molecular features and pathophysiology. Herein, we present a case of a patient who was suspected of metastatic liver cancer and confirmed as lymphocyte-rich HCC pathologically. A 78-year-old woman who underwent a right hemicolectomy for colon cancer was referred to our hospital for a newly detected liver mass. We could not make a decision because of insufficient evidence for diagnosis from imaging studies. After resection, we found that it was a lymphocyte-rich HCC. The pathologic features and prognostic trends of this subtype are also discussed.

Citations

Citations to this article as recorded by

Characterization of lymphocyte‐rich hepatocellular carcinoma and the prognostic role of tertiary lymphoid structures
Bokyung Ahn, Hee‐Sung Ahn, Jinho Shin, Eunsung Jun, Eun‐Young Koh, Yeon‐Mi Ryu, Sang‐Yeob Kim, Chang Ohk Sung, Ju Hyun Shim, JeongYeon Hong, Kyunggon Kim, Hyo Jeong Kang
Liver International.2024; 44(5): 1202. CrossRef
Uncommon variants of hepatocellular carcinoma: Not one size fits all
Reetu Kundu, Nalini Gupta, Debajyoti Chatterjee, Ajay Duseja
Diagnostic Cytopathology.2022; 50(1): 28. CrossRef

Review Articles

Update on Pathologic and Radiologic Diagnosis of Combined Hepatocellular-Cholangiocarcinoma: Hyungjin Rhee, Jae Hyon Park, Young Nyun Park; J Liver Cancer. 2021;21(1):12-24. Published online March 31, 2021; DOI: https://doi.org/10.17998/jlc.21.1.12

6,807 Views
325 Downloads
4 Citations

Abstract PDF

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a malignant primary liver carcinoma characterized by the unequivocal presence of both hepatocytic and cholangiocytic differentiation within the same tumor. Recent research has highlighted that cHCC-CCAs are more heterogeneous than previously expected. In the updated consensus terminology and WHO 2019 classification, “classical type” and “subtypes with stem-cell features” of the WHO 2010 classification are no longer recommended. Instead, it is recommended that the presence and percentages of various histopathologic components and stem-cell features be mentioned in the pathologic report. The new terminology and classification enable the exchange of clearer and more objective information about cHCC-CCAs, facilitating multi-center and multinational research. However, there are limitations to the diagnosis of cHCC-CCA by imaging and biopsy. cHCC-CCAs showing typical imaging findings of HCC could be misdiagnosed as HCC and subjected to inappropriate treatment, if other clinical findings are not sufficiently considered. cHCC-CCAs showing at least one of the CCA-like imaging features or unusual clinical features should be subjected to biopsy. There may be a sampling error for the biopsy diagnosis of cHCC-CCA. An optimized diagnostic algorithm integrating clinical, radiological, and histopathologic information of biopsy is required to resolve these diagnostic pitfalls.

Citations

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Enhancing liver cirrhosis varices and CSPH risk prediction with spleen stiffness measurement using 100-Hz probe
Jeong-Ju Yoo, Sun Ah Maeng, Young Chang, Sae Hwan Lee, Soung Won Jeong, Jae Young Jang, Gab Jin Cheon, Young Seok Kim, Hong Soo Kim, Sang Gyune Kim
Scientific Reports.2024;[Epub] CrossRef
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Noor Fatima Majeed, Mathew Macey, Marta Braschi Amirfarzan, Sheida Sharifi, Jeremy R Wortman
Abdominal Radiology.2024;[Epub] CrossRef
Differentiation between hepatic angiomyolipoma and hepatocellular carcinoma in individuals who are not at-risk for hepatocellular carcinoma
Sungtae Park, Myeong-Jin Kim, Kyunghwa Han, Jae Hyon Park, Dai Hoon Han, Young Nyun Park, Jaehyo Kim, Hyungjin Rhee
European Journal of Radiology.2023; 166: 110957. CrossRef
The Human TOR Signaling Regulator Is the Key Indicator of Liver Cancer Patients’ Overall Survival: TIPRL/LC3/CD133/CD44 as Potential Biomarkers for Early Liver Cancers
Soo Young Jun, Hyang Ran Yoon, Ji-Yong Yoon, Su-Jin Jeon, Jeong-Ju Lee, Debasish Halder, Jin-Man Kim, Nam-Soon Kim
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Histopathological Variants of Hepatocellular Carcinomas: an Update According to the 5th Edition of the WHO Classification of Digestive System Tumors: Haeryoung Kim, Mi Jang, Young Nyun Park; J Liver Cancer. 2020;20(1):17-24. Published online March 31, 2020; DOI: https://doi.org/10.17998/jlc.20.1.17

15,797 Views
1,065 Downloads
33 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) is heterogeneous in pathogenesis, phenotype and biological behavior. Various histopathological features of HCC had been sporadically described, and with the identification of common molecular alterations of HCC and its genomic landscape over the last decade, morpho-molecular correlation of HCC has become possible. As a result, up to 35% of HCCs can now be classified into histopathological variants, many of which have unique molecular characteristics. This review will provide an introduction to the variously described histopathological variants of HCC in the updated WHO Classification of Digestive System Tumors.

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Journal of Pathology Informatics.2024; 15: 100357. CrossRef
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Original Article

Loss of Liver Fatty Acid Binding Protein Expression in Hepatocellular Carcinomas is Associated with a Decreased Recurrence-Free Survival: Haeryoung Kim, Hyejung Lee, Young Nyun Park; J Liver Cancer. 2015;15(1):30-35. Published online March 31, 2015; DOI: https://doi.org/10.17998/jlc.15.1.30

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1 Citation

Abstract PDF

Background/Aims
Loss of liver fatty acid binding protein (LFABP) expression by immunohistochemistry is a useful marker for the identification of hepatocyte nuclear factor 1α (HNF1α)- inactivated hepatocellular adenomas; however, the expression status of LFABP in hepatocellular carcinomas (HCCs) is still unclear. We aimed to investigate the expression status of LFABP in HCCs and examine the clinicopathological characteristics of LFABP-negative HCCs.
Methods
Immunohistochemical stains LFABP, K19 (mouse monoclonal, Dako, Glostrup, Denmark) and EpCAM (mouse monoclonal, Calbiochem, Darmstadt, Germany) were performed on tissue microarray sections from 188 surgically resected HCCs, and the association between LFABP expression status and the clinicopathological features, survival and “stemness”-related marker expression status were analyzed.
Results
Loss of LFABP expression was noted in 30 (16%) out of 188 HCCs. LFABP-negative HCCs were associated with a decreased recurrence-free survival (LFABP-negative: 17.0 ± 4.84 months [95% confidence interval [CI]: 7.5–26.5 months] versus LFABP-positive: 51.0 ± 8.7 months [95% CI: 34.0–68.0 months]; P=0.004). HCCs with LFABP expression loss were more frequently larger and showed more frequent vascular invasion, although not statistically significant; and an inverse correlation was seen between LFABP expression and K19 expression status (P=0.001).
Conclusions
Loss of LFABP expression is seen in HCCs, and is associated with a decreased recurrence-free survival.

Citations

Citations to this article as recorded by

Hepatocellular adenomas: recent updates
Haeryoung Kim, Young Nyun Park
Journal of Pathology and Translational Medicine.2021; 55(3): 171. CrossRef

Case Reports

A Case of Advanced Hepatocellular Carcinoma which was Supervening with Renal Cell Cancer Cured by Repeated Transarterial Chemoembolization and Sorafenib after Resection: Bun Kim, Jae Hoon Min, Seung Up Kim, Jun Yong Park, Kwang Hoon Lee, Do Youn Lee, Jin Sub Choi, Young Deuk Choi, Nam Hoon Cho, Young Nyun Park, Sang Hoon Ahn, Kwang Hyub Han, Chae Yoon Chon, Do Young Kim; Journal of the Korean Liver Cancer Study Group. 2012;12(1):51-57. Published online February 28, 2012

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Abstract PDF: Advanced hepatocellular carcinoma (HCC) is difficult to treat and the survival is poor. Here, we present a patient diagnosed as advanced HCC (stage IIIa) which was supervening with early renal cell cancer (stage I). The patient was treated with pre-operational transarterial chemoembolization (TACE) and surgical resection (right hepatectomy, right nephrectomy, and cholecystectomy). Sorafenib were taken continually after surgery. Multiple recurred HCC nodules in remnant liver were detected 2 months later after surgery. Combined treatment modalities including 4 sessions of TACE, and 12 cycles of 5-flurouracil (FU)/carboplatin based hepatic arterial infusional chemotherapy (HAIC) induced complete response. After the diagnosis of advanced HCC, the patient survived 36 months and experienced disease-free status for 19 months.

A Case of Early Recurred Hepatocellular Carcinoma with Initial Expectation of Good outcome by Surgical Resection: Jung Min Lee, Jun Yong Park, Do Young Kim, Kyung Sik Kim, Young Nyun Park, Myeong-Jin Kim, Chae Yoon Chon, Kwang-Hyub Han; Journal of the Korean Liver Cancer Study Group. 2009;9(1):41-44. Published online June 30, 2009

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Abstract PDF: Hepatocellular carcinoma (HCC) is one of the cancers with poor prognosis as HCC develops on base of cirrhosis in majority cases, which requires multidisciplinary approach. If feasible, however, surgical resection is the choice of treatment, and many previous studies and guidelines offered appropriate indications for surgical resection; firstly, preservation of liver function should be confirmed with traditional Child-Pugh classification or more recently with Indocyanine Green retention test or absence of portal hypertension. Secondly, several variables about the size, number, and vascular invasion of tumor should be taken into consideration. It is suggested that to lessen the risk of recurrence gross vascular invasion be absent and the number of tumor be single. Regarding the size of tumor, although risk of dissemination increases with size, some tumors may grow as a single mass and thus the size of tumor is not a clear-cut limiting factor. Based on above suggestions, we herein offer our experience of a patient with initial hopeful expectation of good outcome with surgical resection, but who eventually turned out to result in disseminated tumor recurrence. Further study, maybe regarding a combination of adjuvant or neoadjuvant transarterial chemoembolization/chemotherapy or radiotherapy, is necessary on how to manage such patient.

A Case of Hepatocellular Carcinoma in a Pregnant Patient in Twenties: Kang Kook Choi, Young Ju Hong, Sae Byeol Choi, Nam Joon Yi, Shin Hwang, Young Nyun Park, Jin Sub Choi, Kyung Suk Suh, Chae Yoon Chon, Kyung Sik Kim; Journal of the Korean Liver Cancer Study Group. 2009;9(1):76-81. Published online June 30, 2009

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Abstract PDF: Hepatocellular carcinoma (HCC) in pregnancy is very rare. The cirrhosis which is present in the majority of patients with HCC induces infertility. The diagnostic methods and treatment modalities in HCC during pregnancy are different from those of usual types of other HCC. A 26-year-old, 32th-gestational-week pregnant female was sent to our hospital because of abnormal liver function test. A 1.5cm sized mass was identified in segment 6 of liver which was compatible to AJCC stage I. She did not have any other medical history except Hepatitis B Virus carrier and the HBs Ag of her mother also was positive. At the 40th gestational week, the female baby was delivered uneventfully. And then she underwent the transarterial chemoembolization (TACE) following the Rt. Hemihepatectomy. Since she underwent a surgical resection, the tumors have been recurred in the remnant liver only. Whenever the tumors were founded, the aggressive surgical approaches were performed including 3 times of hepatic resection with TACE or TACI. She is still alive with good general condition and normal liver function for 9 years since the first diagnosis was made. Therefore an extremely rare case of hepatocellular carcinoma in pregnancy is treated successfully because of aggressive therapies.

A Case of Curative Resection of Advanced Hepatocellular Carcinoma After Localized Concurrent Chemo-Radiation Therapy: Wonseok Kang, Ki Tae Yoon, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Chae Yoon Chon, Kyung Sik Kim, Young Nyun Park, Jin Sil Seong, Kwang Hyub Han; Journal of the Korean Liver Cancer Study Group. 2008;8(1):98-101. Published online June 30, 2008

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Abstract PDF: Most patients with advanced hepatocellular carcinoma (HCC) are not suitable candidates for surgical treatment at the time of diagnosis because of poor liver function, extensive tumor involvement of the liver, vascular involvement, and/or intra/extrahepatic metastasis. We attempted localized concurrent chemo-radiation therapy (CCRT) followed by hepatic arterial infusion chemotherapy (HAIC) in patients having locally advanced HCC with vascular involvement and preserved hepatic function. We report a case of locally advanced HCC patient who became surgically resectable by downstaging after localized CCRT followed by HAIC. Localized CCRT was performed with a total radiation dose of 4,500 cGy (180 cGy × 25 times) and hepatic arterial infusion of 5-fluorouracil (5-FU, 500 mg/day) via implantable port system during the first and the last weeks of the radiotherapy. Following localized CCRT, the patient was scheduled to receive HAIC with 5-FU (500 mg/m2 for 5 hours, days 1～3) and cisplatin (60 mg/m2 for 2 hours, day 2) every 4 weeks. Marked contraction of HCC was noted on follow up computerized tomography (CT) and positron emission tomography (PET) after localized CCRT and HAIC, and subsequently surgical resection with curative aim was performed. The patient is in complete remission status without recurrence to date.

Review Article

Primary hepatic carcinoma with mixed features: Young Nyun Park; Journal of the Korean Liver Cancer Study Group. 2007;7(1):13-15. Published online June 30, 2007

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Case Reports

A Case of Focal Nodular Hyperplasia-like Nodules in Cirrhosis: Young Joon Yoon, Ki Tae Yoon, Jun Yong Park, Hyun Woong Lee, Hwa Sook Kim, Jae Kyung Kim, Young Nyun Park, Kwang-Hyub Han, Chae Yoon Chon, Young Myung Moon, Mi-Suk Park, Sang Hoon Ahn; Journal of the Korean Liver Cancer Study Group. 2007;7(1):41-44. Published online June 30, 2007

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41 Downloads

Abstract PDF: Focal nodular hyperplasia (FNH) usually occurs in non-cirrhotic livers and was defined as a nodule composed of benign appearing hepatocytes occurring in a liver that is otherwise histologically normal or nearly normal. However, due to improvements in imaging techniques and pathological evaluation of explant livers, a focal lesion that is very similar to the classic form of focal nodular hyperplasia that occurs in cirrhotic liver has been described by several reports. Therefore, the term FNH-like nodules has been proposed. In this report, we report a case of focal nodular hyperplasia-like nodules in cirrhosis. A 59 year old woman with known hepatitis B virus infection visited our institution for routine check up. She was diagnosed as having liver cirrhosis and 3.5 cm sized liver mass on abdomen ultrasonography (US). Because tumor marker was negative and US findings are not compatible with hepatocellular carcinoma, other imaging modalities were performed. Magnetic resonance imaging (MRI) documented a 3.5 cm sized hypervascular nodule with internal aberrant vascular structure and multiple small sized nodules in remaining liver. Needle biopsy was targeted to the liver main mass. Microscopic finding revealed FNH-like nodule and underlying liver cirrhosis.

Two cases of Vessel invasion of Hepatocellular carcinoma: Sae Byeol Choi, Jae Yeon Seok, Kyung Sik Kim, Young Nyun Park, Kwang-Hyub Han, Jong Tae Lee; Journal of the Korean Liver Cancer Study Group. 2007;7(1):71-76. Published online June 30, 2007

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Abstract PDF: Despite growing information on the clinical behavior of hepatocellular carcinoma(HCC), the histologic features associated with survival are not well characterized. Several different staging systems are suggested for use in predicting the prognosis of HCC. American Joint Committee on Cancer/International Union Against Cancer Staging System (AJCC/UICC) 6th edition divided T stages according to vessel invasion, T1 without microvessel invasion, T2 showing microvessel invasion and T3 showing major vessel invasion. The vessel invasion is generally considered a poor prognostic factor for HCC. Our report of the two patients with HCC run along similar terms. The patient diagnosed HCC with microvessel invasion underwent left lateral sectionectomy. Although the presence of microvessel invasion was found, this patient has survived without any recurrence for over 5 years now. The other patient underwent S8 segmentectomy and lived 10 years disease-free. After 10 years, although an intrahepatic recurred HCC successfully treated with local therapy, the recurred and newly developed multiple lesions were found again leading to a decision to perform operation. The HCC invaded into the portal vein and constituted portal vein thrombosis. The patient expired after 3 months postoperatively due to intrahepatic dissemination of the tumor. Therefore the impact of the vascular invasion on long-term survivors remains to be determined.

A Case of Advanced Hepatocellular Carcinoma with Inferior Vena Caval Invasion, Resected with a Curative Aim after Concurrent Chemo-Radiation Therapy: Seung Up Kim, Kwang Hyub Han, Jin Sil Sung, Do Young Kim, Sang Hoon Ahn, Gyeong Sig Kim, Young Nyun Park, Chae Yoon Chon; Journal of the Korean Liver Cancer Study Group. 2007;7(1):77-81. Published online June 30, 2007

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Abstract PDF: Hepatocellular carcinoma (HCC) with tumor thrombus in inferior vena cava (IVC) is difficult to treat. Therefore, there are no specific treatment modalities for such case. Here, we present a patient diagnosed as hepatocellular carcinoma with tumor thrombus in inferior vena cava (stage IVa). The patient was treated with concurrent chemo-radiation therapy (CCRT) for 5 weeks. After that, tumor size was markedly decreased, and 9th courses of additional intra-arterial chemotherapy were performed. Follow-up positron emission tomography- computed tomography (PET-CT) showed shrinked hepatocellular carcinoma and right lobe, disappearance of IVC tumor thrombus, decreased size of right hepatic vein thrombus and a faint uptake at gallbladder. Residual malignancy could not be excluded. So, right hepatic lobectomy with a curative aim was performed and its result was successful.

Review Articles

Well-differentiated Samll Hepatocellular Carcinoma, Early Hepatocellular Carcinoma and Dysplastic Nodule: Young Nyun Park; Journal of the Korean Liver Cancer Study Group. 2004;4(1):7-11. Published online June 30, 2004

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Pathologic Findings of Variants and Uncommon Types of Primary Liver Cancers: Young Nyun Park; Journal of the Korean Liver Cancer Study Group. 2002;2(1):27-35. Published online July 31, 2002

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