Journal of Pathology and Translational Medicine

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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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.

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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,
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Fatal rupture of hepatic adenomatosis: Autopsy case and review of the literature
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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

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.

Citations

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Stemness markers in hepatocellular carcinoma of Eastern vs. Western population: Etiology matters?
Caecilia HC Sukowati, Korri El-Khobar, Chyntia Olivia Maurine Jasirwan, Juferdy Kurniawan, Rino Alvani Gani
Annals of Hepatology.2024; 29(1): 101153. CrossRef
Research progress and prospects of AFP-positive gastric cancer
Long Zhao, Changjiang Yang, Yilin Lin, Shan Wang, Yingjiang Ye, Zhanlong Shen
Foregut Surgery.2022; 2(1): 29. CrossRef
SALL4 and microRNA: The Role of Let-7
Jun Liu, Madeline A. Sauer, Shaza G. Hussein, Junyu Yang, Daniel G. Tenen, Li Chai
Genes.2021; 12(9): 1301. CrossRef
Hepatoid Teratoma, Hepatoid Yolk Sac Tumor, and Hepatocellular Carcinoma
Khaleel I. Al-Obaidy, Sean R. Williamson, Nathan Shelman, Muhammad T. Idrees, Thomas M. Ulbright
American Journal of Surgical Pathology.2021; 45(1): 127. CrossRef
Targeting an Inducible SALL4-Mediated Cancer Vulnerability with Sequential Therapy
Junyu Yang, Chong Gao, Miao Liu, Yao-Chung Liu, Junsu Kwon, Jun Qi, Xi Tian, Alicia Stein, Yanjing V. Liu, Nikki R. Kong, Yue Wu, Shenyi Yin, Jianzhong Xi, Zhiyuan Chen, Kalpana Kumari, Hannan Wong, Hongbo Luo, Leslie E. Silberstein, Julie A.I. Thoms, Ash
Cancer Research.2021; 81(23): 6018. CrossRef
Lipoprotein‐Like Nanoparticle Carrying Small Interfering RNA Against Spalt‐Like Transcription Factor 4 Effectively Targets Hepatocellular Carcinoma Cells and Decreases Tumor Burden
William Cruz, Huang Huang, Brian Barber, Elisa Pasini, Lili Ding, Gang Zheng, Juan Chen, Mamatha Bhat
Hepatology Communications.2020; 4(5): 769. CrossRef
Hepatoid adenocarcinoma of the stomach: a unique subgroup with distinct clinicopathological and molecular features
Yakun Wang, Li Sun, Zhongwu Li, Jing Gao, Sai Ge, Cheng Zhang, Jiajia Yuan, Xicheng Wang, Jian Li, Zhihao Lu, Jifang Gong, Ming Lu, Jun Zhou, Zhi Peng, Lin Shen, Xiaotian Zhang
Gastric Cancer.2019; 22(6): 1183. CrossRef
Gynecologic Serous Carcinoma: An Immunohistochemical Analysis of Malignant Body Fluid Specimens
Shuyue Ren, William Klump
Archives of Pathology & Laboratory Medicine.2019; 143(6): 677. CrossRef
The pluripotency network in colorectal cancer pathogenesis and prognosis: an update
Ioannis A Voutsadakis
Biomarkers in Medicine.2018; 12(6): 653. CrossRef
Cancer stem cells in hepatocellular carcinoma: an overview and promising therapeutic strategies
Nuozhou Wang, Shanshan Wang, Ming-Yue Li, Bao-guang Hu, Li-ping Liu, Sheng-li Yang, Shucai Yang, Zhongqin Gong, Paul B. S. Lai, George G. Chen
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DNA demethylation induces SALL4 gene re-expression in subgroups of hepatocellular carcinoma associated with Hepatitis B or C virus infection
H Fan, Z Cui, H Zhang, S K Mani, A Diab, L Lefrancois, N Fares, P Merle, O Andrisani
Oncogene.2017; 36(17): 2435. CrossRef
Higher expression of SALL4 predicts poor cancer prognosis: A meta-analysis
Hongyu Shen, Liangpeng Li, Dandan Wang, Sujin Yang, Xiu Chen, Siying Zhou, Shanliang Zhong, Jianhua Zhao, Jinhai Tang
Cancer Biomarkers.2017; 19(4): 365. CrossRef
SALL4 suppresses PTEN expression to promote glioma cell proliferation via PI3K/AKT signaling pathway
Chuanjin Liu, Haibin Wu, Yanyan Li, Liang Shen, Renchun Yu, Hongwei Yin, Ting Sun, Chunming Sun, Youxin Zhou, Ziwei Du
Journal of Neuro-Oncology.2017; 135(2): 263. CrossRef
Liver Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells
Germana Castelli, Elvira Pelosi, Ugo Testa
Cancers.2017; 9(9): 127. CrossRef
Oncofetal gene SALL4 and prognosis in cancer: A systematic review with meta-analysis
Lorenzo Nicolè, Tiziana Sanavia, Nicola Veronese, Rocco Cappellesso, Claudio Luchini, Paolo Dabrilli, Ambrogio Fassina
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SALL4, the missing link between stem cells, development and cancer
Hiro Tatetsu, Nikki R. Kong, Gao Chong, Giovanni Amabile, Daniel G. Tenen, Li Chai
Gene.2016; 584(2): 111. CrossRef
A New Cell Block Method for Multiple Immunohistochemical Analysis of Circulating Tumor Cells in Patients with Liver Cancer
Soo Jeong Nam, Hyun Yang Yeo, Hee Jin Chang, Bo Hyun Kim, Eun Kyung Hong, Joong-Won Park
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Functional and clinical significance of SALL4 in breast cancer
Ebubekir Dirican, Mustafa Akkiprik
Tumor Biology.2016; 37(9): 11701. CrossRef
MicroRNA-33b suppresses the proliferation and metastasis of hepatocellular carcinoma cells through the inhibition of Sal-like protein 4 expression
Qinggang Tian, Yao Xiao, Yanting Wu, Yun Liu, Zhiqing Song, Wenfeng Gao, Jing Zhang, Jingling Yang, Yuguo Zhang, Tuankui Guo, Furong Dai, Zhigang Sun
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

Fine Needle Aspiration Cytology of Hepatoblastoma: Report of Two Cases.: Young Nyun Park, Kwang Gil Lee, Chan II Park; Korean J Cytopathol. 1990;1(1):98-102.

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Abstract PDF: Hepatoblastoma(HB) is a rare embryonic malignant tumor of the liver. Most morphological studies on HB have limited to the histological characteristics and only 3 cases of HB have been described in the cytology literature. We present 2 cases of HB occurring in children aged 1 year and 3 years, respectively. The distinctive cytologic features of fine needle aspiration of HB were clusters of tumor cells showing acinar and trabecular pattern, smaller tumor cells with a high nuclear-cytoplasmic ratio and hyperchromatic nuclei having prominent nucleoli, and the presence of extramedullary hematopoiesis and osteoid material. These features were also found in the cell block and the biopsy specimen, and appeared very useful in the differentiation of HB from hepatocellular carcinoma.

Fine needle aspiration cytology of malignant thymoma: two cases of invasive thymoma and thymic carcinoma.: Mee Yon Cho, Young Nyun Park, Kwang Gil Lee; Korean J Cytopathol. 1991;2(1):36-42.

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Abstract PDF: We report 4 cases of malignant thymoma which were composed of 2 cases of invasive thymoma and 2 cases of thymic carcinoma. The cytologic findings of invasive thymoma were similar to those of benign thymoma. The distinctive cytologic features of thymic carcinoma were necrotic background, irregular clusters and individually scattered arrangement of anaplastic epithelial cells, and some scattered mature small lymphocytes. These findings may be found in the Hodgkin'slymphoma, seminoma, and metastatic squamous cell carcinoma, undifferentiated carcinoma, and large cell carcinoma of the. lung. But, the feature of irregular clustering of anaplastic epithelial cell having scanty cytoplasm was different from Hodgkin'slymphoma and seminoma. Clinical and radiologic findings as well as cytologic finding were helpful in differential diagnosis of thymic carcinoma from metastatic carcinoma.

Clinicopathologic Characteristics of Left-Sided Colon Cancers with High Microsatellite Instability.: Sang Kyum Kim, Junjeong Choi, Hyun Ki Kim, Young Nyun Park, Si Young Song, Hoguen Kim; Korean J Pathol. 2009;43(5):428-434.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.428

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Abstract PDF

BACKGROUND
High microsatellite instability (MSI-H) colorectal carcinomas (CRCs) with numerous mutations in the microsatellite sequence are characterized by a right-sided preponderance, frequent peritumoral and intratumoral lymphocytic infiltration, and frequent mucin production. However, no study has correlated anatomic site and type of genetic changes with clinicopathologic changes.
METHODS
We analyzed the histopathologic features of 135 MSI-H CRCs and compared them to 140 microsatellite stable (MSS) CRCs. Histopathologic changes in MSI-H were further analyzed according to anatomic sites and genetic changes.
RESULTS
MSI-H CRCs showed previously reported clinicopathologic findings; a right-sided preponderance, an increased number of mucinous carcinomas, and peritumoral lymphoid reactions (p<0.001 for each variable). Increased serum CEA levels showed an MSS CRC preponderance (p=0.013). We further analyzed the histologic differences between right- and left-sided MSI-H tumors. We found that MSI-H CRCs on both sides had similar clinicopathologic findings, except for higher tumor stage (p=0.048) and less frequent abnormal CEA levels in left-sided MSI-H tumors (p=0.027). We found that not all clinicopathologic features were different between hereditary nonpolyposis colorectal cancers (HNPCCs) and sporadic MSI-H CRCs.
CONCLUSIONS
These findings indicate that MSI-H CRCs of the left colon have similar clinicopathologic characteristics as right-sided MSI-H CRCs. We did not find any significant clinicopathological difference between HNPCCs and sporadic MSI-H CRCs.

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Fibroblast Growth Factor Receptor 1 Gene Copy Number and mRNA Expression in Primary Colorectal Cancer and Its Clinicopathologic Correlation
Yoonjin Kwak, Soo Kyung Nam, An Na Seo, Duck-Woo Kim, Sung-Bum Kang, Woo Ho Kim, Hye Seung Lee
Pathobiology.2015; 82(2): 76. CrossRef

Primary Biliary Cirrhosis-Autoimmune Hepatitis Overlap Syndrome.: Jong Yup Bae, Young Nyun Park, Chanil Park; Korean J Pathol. 1997;31(1):87-90.

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Abstract PDF: Cases sharing features of both primary biliary cirrhosis and autoimmune hepatitis have been reported as a mixed type, overlap syndrome, immunocholangitis and autoimmune cholangiopathy. A primary biliary cirrhosis- autoimmune hepatitis overlap syndrome is unusual and characterized by overlapping features; cholestasis, high titer of alkaline phosphatase, bile duct damage and granulomas in the liver biopsy, high antinuclear antibody, increased IgG and IgM and intra-acinar hepatitis with piecemeal necrosis. Autoimmune mechanisms are thought to play a major role in the pathogenesis of the overlapping syndrome and the bases of immunosuppressive therapy. A 58-year-old female patient shows overlapping clinical and laboratory findings, chronic active hepatitis in initial liver biopsy which transits to primary biliary cirrhosis with cholangitis and granulomas. This is a case of hepatobiliary lesion showing overlapping features of both primary biliary cirrhosis and autoimmune hepatitis over 3-year period.

Clonality of Large Regenerative Nodule Accompanied by Hepatocellular Carcinoma.: Zhe Piao, Bong Kyun Chun, Woo Jung Lee, Young Nyun Park, Ho guen Kim, Chanil Park; Korean J Pathol. 1997;31(9):884-890.

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Abstract PDF: In order to clarify the preneoplastic nature of large regenerative nodules without dysplastic change, we analysed the clonality of hepatocellular carcinomas (HCCs) and large nodules, diameter > or =0.5 cm, of cirrhotic liver by X-linked human androgen receptor (HUMARA) gene assay, using the principle of random X chromosome methylation and inactivation in female. Ten cases of HCC and 5 cases of large nodules without dysplasia from 9 female patients were selected. All the tumors, large nodules and paired normal control cells were selectively microdissected from deparaffinized hematoxylin and eosin stained slides. Genomic DNA was isolated and digested with HhaI. Polymerase chain reaction(PCR) amplication of the HUMARA locus was performed using 32P-a-dCTP containing PCR mixtures. The PCR amplified products were separated by gel electrophoresis and analysed by autoradiography. Nine HCCs from 8 patients were monoclonal and 1 case was polyclonal and the remaining 1 case was not polymorphic at the HUMARA locus. The HCC case which showed polyclonality contained many inflammatory cells. All the large nodules were polyclonal by HUMARA assay. These results suggest that all or most of the cells composing the large regenerative nodules without dysplasia are polyclonal. This assay may be informative for the differentiation between regenerative and preneoplastic nodules in cirrhotic liver and the size of nodule may be not important in hepatocarcinogenesis.

Case Report

Adreno-Hepatic Fusion: A case report.: Kyung Moo Yang, Young Nyun Park, Chan Il Park; Korean J Pathol. 1998;32(5):385-387.

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Abstract: Adreno-hepatic fusion is rare condition defined as adhesion of the liver and right adrenal cortex with close intermingling of the respective parenchyme. It is suggested to be an aging phenomenon, because its incidence is much higher in older age group. Clinically it may pose a problem of operability of the organ involved. We report a case of incidentally found adreno-hepatic fusion in a 49 year old female patient with adenocarcinoma of the sigmoid colon. The segementectomy of VIII segement of the liver was done due to a 6 4 cm sized metastatic nodule of adenocarcioma. Pathological examination of the liver revealed an ovoid shaped, 1 0.5 cm sized adrenal cortical tissue. It was subcapsularly located and about 1cm apart from the metastatic adenocarcinoma with an intervening normal hepatic tissue. The adrenal tissue was mainly composed of zona fasciculata without medullary tissue. In the interphase, the adrenal tissue and liver tissue were admixed closely and partially septated by thin fibrous tissue. There was no inflammatory response to the heterotropically located adrenal tissue and there was no symptom related to the adrenal gland.

Original Articles

Histological Grading and Staging of Chronic Hepatitis Standardized Guideline Proposed by the Korean Study Group for the Pathology of Digestive Diseases .: Young Nyun Park, Ho guen Kim, Chae Yoon Chon, Jae Bok Park, Jin Hee Sohn, Seung Ha Yang, Eun Sil Yu, Mi Seon Lee, Ja June Jang, Hee Kyung Chang, Jong Jae Jeong, Dae Young Kang, Yong Il Kim, Chan Il Park; Korean J Pathol. 1999;33(5):337-346.

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Abstract PDF: The terms chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and chronic lobular hepatitis (CLH) should be discontinued in favor of etiologic terminology. The activity of necro-inflammation and the degree of fibrosis should be evaluated for grading the severity and for the stage of disease. Members of the Korean Study Group for the Pathology of Digestive Diseases reviewed 30 cases of chronic hepatitis and reached the following consensus: 1) The pathology report of the biopsy samples with features of chronic hepatitis should include the etiology, grade and stage. 2) Grade and stage should be semiquantitatively evaluated as none, minimal, mild, moderate and severe. 3) For grading, lobular activity and periportal activity should be evaluated, separately. 4) To avoid confusion with other grading systems, simple report using descriptive terms rather than numerical records is recommended in daily practice. Criteria for each grade and stage should be presented and discussed. Histologic grading and staging of chronic hepatitis by new standardized guidelines will give more information about the prognosis as well as the present status of hepatitis. The terms CAH, CPH and CLH may be used in parentheses to facilitate relearning.

p21 Protein Expression and Cell Proliferation Activity in Human Multistep Hepatocarcinogenesis.: Kye Weon Kwon, Young Nyun Park, Chan Il Park; Korean J Pathol. 2000;34(5):325-330.

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Abstract PDF: p21 is a universal inhibitor of cyclin-dependent kinase (cdk) and of cell-cycle progression. p21 expression is variable according to the type of tissue and the pathologic condition. To study the role of p21 in the multistep hepatocarcinogenesis, the expression of p21, p53 and Ki-67 was investigated in 53 cases of inactive liver cirrhosis, 4 cases of low grade dysplastic nodules, 3 cases of high grade dysplastic nodules, 7 cases of early hepatocellular carcinomas (HCCs), 27 cases of small HCCs (< or =3 cm), and 52 cases of advanced HCCs (>3 cm). p21 expression was not detected in liver cirrhosis, low grade dysplastic nodules, high grade dysplastic nodules and early HCCs which were mitotically inactive. p21 expression was significantly increased in small HCCs and advanced HCCs which were mitotically active. p21 expression was significantly correlated with Ki-67 labelling indices. p53 protein was not expressed in liver cirrhosis, dysplastic nodules, and early HCCs. The expression of p53 protein was, however, significantly increased in small and advanced HCCs. The p21 expression was not correlated with p53 expression. Therefore, p21 is suggested to play a role in the mitotically active small and advanced HCCs, but not in the mitotically inactive lesion of dysplastic nodules and early HCC in multistep hepatocarcinogenesis. These findings suggest that homeostatic mechanism of growth control is not totally destroyed in HCC.

Case Reports

Hepatic Veno-occlusive Disease Developed after Irradiation: A report of three cases .: Kyoungsoo Har, Se Hoon Kim, Young Nyun Park, Chanil Park; Korean J Pathol. 2000;34(5):381-385.

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Abstract PDF: Hepatic veno-occlusive disease (VOD) is a rare disease due to occlusion of the terminal hepatic venules and/or sublobular veins, which is a result of endothelial damage from pyrrolizidine alkaloids in herbal teas, irradiation of the liver, or chemotherapy particularly in association with bone marrow transplantation. We recently experienced three cases of VOD developed after radiation therapy. Two cases occurred in hepatocellular carcinoma patients of a 37-year-old man with B viral chronic hepatitis and a 22-year-old man with B viral cirrhosis and the other in a 64-year-old patient with esophageal squamous cell carcinoma. For the treatment of hepatocellular carcinoma, chemoembolization with lipiodol and adriamycin, and external irradiation on the liver mass were done. The total radiation dose was 5400 cGy and 3000 cGy in each case. Five months and 3 months after irradiation, respectively, the resected liver masses showed extensive necrosis due to pre-operative treatment. To treat esophageal carcinoma, pre-operative concurrent chemotherapy of 5-FU and radiation of 4500 cGY were done. One month after irradiation, the radical esophgectomy and wedge biopsy of the liver were done. The liver of all 3 cases showed a dark red appearance with severe congestion in contrast to the pale brown normal liver, which was not included in the radiation field. On micoscopic examination, the terminal hepatic venules and sublobular veins showed subintimal edema, fibrin deposition, and partial or total luminal occlusion by loose fibrous tissue. The centrizonal sinusoids were markedly dilatated and congested with atrophy of hepatocytes.

Non-cirrhotic Portal Hypertension in Idiopathic Myelofibrosis: A case report.: Sung Eun Kim, Young Nyun Park, Woo Ick Yang, Jin Sup Choi, Chanil Park; Korean J Pathol. 2000;34(5):386-388.

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Abstract PDF: We report a case of non-cirrhotic portal hypertension in a 73 year-old woman, who had 19-year history of idiopathic myelofibrosis. There were esophageal varix, splenomegaly, and ascites. The biopsied liver showed irregular sinusoidal/ perisinusoidal fibrosis and occasional central-to-central fibrous connection. In areas with extensive fibrosis, coarse collagen fibers filled the sinusoidal spaces and compressed hepatocytes. However, nodular regeneration was absent. Double immunohistochemical stain for smooth muscle actin and proliferation cell nuclear antigen (PCNA) revealed diffusely activated stellate cells, some of which showed nuclear PCNA staining. There was also extramedullary hematopoiesis with bizarre megakaryocytes. The portal vein and its branches were patent. Idiopathic myelofibrosis is a rare cause of non-cirrhotic portal hypertension: the portal hypertension was considered to be the result of sinusoidal/perisinusoidal fibrosis in this case.

Original Articles

Pathological Analysis of 62 Liver Biopsy Cases with Hepatocellular Cholestasis: Drug and Toxin Induced Liver Injury.: Min Sun Cho, Young Nyun Park, Myeong Jin Kim, Kwang Jo Chae, Chanil Park; Korean J Pathol. 2001;35(2):123-128.

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Abstract PDF: BACKGROUND
Hepatocellular cholestasis denotes the alteration of bile secretion by hepatocytes. The causes, degree of hepatocyte injury and concomitant bile duct loss are considered to influence the clinical course.
METHODS
The causes and pathological features of hepatocellular cholestasis were analyzed in 62 cases of liver biopsies; and the causes of primary biliary cirrhosis, primary sclerosing cholangitis, and biliary obstruction were not included.
RESULTS
The mean age of the patients was 42.2 years, and the ratio of male to female was 1.8:1. Fifty-eight cases (94%) showed cholestatic hepatitis, and 4 cases (6%) showed pure cholestasis without hepatitis activity. The majority of the cases (52 cases, 84%), including 19 cases of herbal medicine, was related to drugs. Loss of bile duct was found in 12 cases (19%), which were all cases of chronic cholestasis. All of them had drug histories, including 9 cases of herbal medicine. Clinical follow-up was performed in 9 out of the 12 cases with bile duct loss, and all of them showed elevated total bilirubin and/or alkaline phosphatase levels for more than 6 months.
CONCLUSION
Drugs are the major cause of hepatocellular cholestatic hepatitis/cholestasis; and information about drugs, including herbal medicines, should be considered for proper evaluation of liver biopsy with hepatocellular cholestasis. Bile duct loss should be evaluated in the cases of chronic hepatocellular cholestasis, especially in drug induced cases.

The Expression of Extracellular Signal Regulated Kinase (ERK) in Non-Small Cell Lung Carcinoma.: Se Hoon Kim, Hyung Jung Kim, Young Nyun Park, Sang Ho Cho; Korean J Pathol. 2001;35(5):361-367.

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Abstract PDF: BACKGROUND
Although it was suggested that constitutive extracellular signal regulated kinase (ERK) activation plays a pivotal role in intracellular signal transduction related to oncogenesis, a consistent relationship between constitutive ERK activation and oncogenesis has not yet been clearly demonstrated. The purpose of this study is to evaluate the expression frequencies and pattern of phosphorylated ERK (p-ERK) in the non-small cell lung carcinoma (NSCLC) and to evaluate whether p-ERK is a useful prognostic factor.
METHODS
One hundred sixty cases of NSCLC tissue specimens were investigated by immunohistochemical staining for p-ERK. Clinicopathologic values (tumor stage, cell type, differentiation and presence of metastasis) and p-ERK expression of normal alveolar pneumocytes around NSCLC were compared with the incidence of tumor p-ERK expression.
RESULTS
Fifty-three out of 160 cases (33%) of NSCLC showed expression of p-ERK. There was no statistical correlation between the expression of p-ERK in the NSCLC neoplastic cells and the corresponding tumor stage, cell type and presence of metastasis. There was statistical significance between the expressions of p-ERK in alveolar pneumocytes around NSCLC (odds ratio: 6.130).
CONCLUSIONS
Based on these results, we suggest that p-ERK expression is not useful in predicting the prognosis of NSCLC. In regard to the theory of "field cancerization" and the phenomenon of "allele-specific loss or allele-specific mutations", the statistically significant p-ERK expression in alveolar pneumocytes around NSCLC suggests that constitutive ERK activation is involved in the early stage of NSCLC carcinogenesis rather than in proliferation, differentiation or metastasis of NSCLC.

Expression of Matrix Metalloproteinase (MMP)-2, MMP-9, Tissue Inhibitor of Metalloproteinase (TIMP)-1 and TIMP-2 in Adenocarcinomas of The Gallbladder.: Jong Yup Bae, Jinsub Choi, Hyun Cheol Chung, Chanil Park, Young Nyun Park; Korean J Pathol. 2003;37(1):1-9.

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Abstract PDF: BACKGROUND
Matrix metalloproteinase (MMP)-2 and MMP-9 degrade type IV collagen and are antagonized by the tissue inhibitors of metalloproteinase (TIMP)-2 and TIMP-1, respectively.
METHODS
We studied by immunohistochemistry the expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 in 72 cases of adenocarcinoma of the gallbladder.
RESULTS
The MMP-2, MMP-9 and TIMP-1 expressions were significantly higher in well/moderately differentiated adenocarcinomas than in poorly differentiated adenocarcinomas, in adenocarcinomas that had invaded the lamina propria/proper muscle than in those that had invaded the perimuscular connective tissue or beyond the serosa, and in adenocarcinomas with fungating growth than in those with infiltrative growth. The TIMP-2 expression showed a similar pattern without statistical significance. Regarding the status of lymph node metastasis, the MMP-2 expression was significantly higher in cases without lymph node metastasis. The MMP-2 and MMP-9 expressions were significantly related to those of TIMP-2 and TIMP-1, respectively, with regard to depth of invasion, differentiation, and growth patterns of the adenocarcinomas.
CONCLUSIONS
MMP-2, MMP-9, TIMP-1 and TIMP-2 are suggested to play important roles in the progression to early invasion of adenocarcinomas, in which the function of MMP-2 is inhibited by TIMP-2.

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