- The Clinicopathological and Prognostic Significance of the Gross Classification of Hepatocellular Carcinoma
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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
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J Pathol Transl Med. 2018;52(2):85-92. Published online November 24, 2017
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DOI: https://doi.org/10.4132/jptm.2017.11.13
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 Abstract
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- 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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Citations
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- SALL4 Expression in Hepatocellular Carcinomas Is Associated with EpCAM-Positivity and a Poor Prognosis
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Hyunjin Park, Hyejung Lee, An Na Seo, Jai Young Cho, Young Rok Choi, Yoo-Seok Yoon, Ho-Seong Han, Young Nyun Park, Haeryoung Kim
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J Pathol Transl Med. 2015;49(5):373-381. Published online August 10, 2015
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DOI: https://doi.org/10.4132/jptm.2015.07.09
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9,055
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Abstract
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- 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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Citations
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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
Therapeutic Advances in Medical Oncology.2018; 10: 175883591881628. CrossRef - 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
Oncotarget.2017; 8(14): 22968. CrossRef - 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
Cancer Research and Treatment.2016; 48(4): 1229. CrossRef - 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
- Chemotherapy-Associated Hepatopathy in Korean Colorectal Cancer Liver Metastasis Patients: Oxaliplatin-Based Chemotherapy and Sinusoidal Injury
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Soo Jeong Nam, Jai Young Cho, Hye Seung Lee, Gheeyoung Choe, Ja June Jang, Yoo-Seok Yoon, Ho-Seong Han, Haeryoung Kim
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Korean J Pathol. 2012;46(1):22-29. Published online February 23, 2012
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DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.22
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6,692
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Abstract
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- Background
Although chemotherapy-related hepatic injury has been reported in colorectal cancer liver metastasis (CRLM) patients, the morphologic changes caused by chemotherapeutic agents and the effect of chemotherapy on postoperative outcome remain ill-defined. A comprehensive review of the morphologic changes in the post-chemotherapy non-neoplastic liver was performed and the clinical effect of preoperative chemotherapy in CRLM patients was analyzed. MethodsHematoxylin-eosin, Masson's trichrome and reticulin-stained slides from non-neoplastic livers obtained from 89 CRLM patients were analyzed, and the clinicopathologic features were correlated with the status of chemotherapy exposure. ResultsHistopathologic features of sinusoidal injury (sinusoidal dilatation, centrilobular perivenular fibrosis, parenchymal extinction lesions, small vessel obliteration, and hepatocyte plate disruption) were significantly more frequent in oxaliplatin-exposed livers (p<0.05). The extent of sinusoidal dilatation was positively correlated with increasing numbers of chemotherapy cycles (p=0.022). Abnormal preoperative liver function tests were more frequently seen (p<0.05) and postoperative total bilirubin was higher in the chemotherapy group (p=0.008). Postoperative morbidity was more common in the chemotherapy group (p=0.044). ConclusionsSinusoidal injury is frequently seen in oxaliplatin-treated livers, and its presence, especially when extensive, should be documented in surgical pathology practice. The recognition of sinusoidal injury may provide helpful guidelines for surgeons in deciding the extent of hepatic resection.
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Citations
Citations to this article as recorded by - Model establishment and microarray analysis of mice with oxaliplatin‑induced hepatic sinusoidal obstruction syndrome
Chen Zhu, Xinwei Cheng, Ping Gao, Qianyan Gao, Ximin Wang, Dong Liu, Xiuhua Ren, Chengliang Zhang
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Chen Zhu, Xiuhua Ren, Dong Liu, Chengliang Zhang
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