Journal of Pathology and Translational Medicine

Original Articles

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

8,526 View
72 Download
18 Web of Science
15 Crossref

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.

Citations

Citations to this article as recorded by

Recent Progress in Systemic Therapy for Advanced Hepatocellular Carcinoma
Narayanan Sadagopan, Aiwu Ruth He
International Journal of Molecular Sciences.2024; 25(2): 1259. CrossRef
Clinicopathological and prognostic value of epithelial cell adhesion molecule in solid tumours: a meta-analysis
Peiwen Ding, Panyu Chen, Jiqi Ouyang, Qiang Li, Shijie Li
Frontiers in Oncology.2023;[Epub] CrossRef
PD-L1 Downregulation and DNA Methylation Inhibition for Molecular Therapy against Cancer Stem Cells in Hepatocellular Carcinoma
Caecilia Sukowati, Loraine Kay D. Cabral, Beatrice Anfuso, Francesco Dituri, Roberto Negro, Gianluigi Giannelli, Claudio Tiribelli
International Journal of Molecular Sciences.2023; 24(17): 13357. CrossRef
EpCAM, Ki67, and ESM1 Predict Hepatocellular Carcinoma Recurrence After Liver Transplantation
Aiat Shaban Hemida, Doha Maher Taie, Moshira Mohamed Abd El-Wahed, Mohammed Ibrahim Shabaan, Mona Saeed Tantawy, Nermine Ahmed Ehsan
Applied Immunohistochemistry & Molecular Morphology.2023; 31(9): 596. CrossRef
The clinical, prognostic and therapeutic significance of liver cancer stem cells and their markers
Izabela Zarębska, Arkadiusz Gzil, Justyna Durślewicz, Damian Jaworski, Paulina Antosik, Navid Ahmadi, Marta Smolińska-Świtała, Dariusz Grzanka, Łukasz Szylberg
Clinics and Research in Hepatology and Gastroenterology.2021; 45(3): 101664. CrossRef
Detection of oncogenic mutations in paired circulating tumor DNA and circulating tumor cells in patients with hepatocellular carcinoma
Zhouhong Ge, Jean C.A. Helmijr, Maurice P.H.M. Jansen, Patrick P.C. Boor, Lisanne Noordam, Maikel Peppelenbosch, Jaap Kwekkeboom, Jaco Kraan, Dave Sprengers
Translational Oncology.2021; 14(7): 101073. CrossRef
Hepatocellular Carcinoma Score and Subclassification Into Aggressive Subtypes Using Immunohistochemical Expression of p53, β-Catenin, CD133, and Ki-67
Asmaa G. Abdou, Nanis S. Holah, Dina S. Elazab, Walaa G. El-Gendy, Mohammed T. Badr, Dalia R. Al-Sharaky
Applied Immunohistochemistry & Molecular Morphology.2021; 29(1): 20. CrossRef
The prognostic significance of neuroendocrine markers and somatostatin receptor 2 in hepatocellular carcinoma
Keigo Murakami, Hiroyuki Kumata, Shigehito Miyagi, Takashi Kamei, Hironobu Sasano
Pathology International.2021; 71(10): 682. CrossRef
Predictors of recurrence and survival of hepatocellular carcinoma: A prospective study including transient elastography and cancer stem cell markers
Hend Ibrahim Shousha, Rabab Fouad, Tamer Mahmoud Elbaz, Dina Sabry, Mohamed Mahmoud Nabeel, Ahmed Hosni Abdelmaksoud, Aisha Mahmoud Elsharkawy, Zeinab Abdellatif Soliman, Ghada Habib, Ashraf Omar Abdelaziz
Arab Journal of Gastroenterology.2020; 21(2): 95. CrossRef
Napabucasin Reduces Cancer Stem Cell Characteristics in Hepatocellular Carcinoma
Ya Li, Qiuju Han, Huajun Zhao, Quanjuan Guo, Jian Zhang
Frontiers in Pharmacology.2020;[Epub] CrossRef
The mRNA Distribution of Cancer Stem Cell Marker CD90/Thy-1 Is Comparable in Hepatocellular Carcinoma of Eastern and Western Populations
An B. Luong, Huy Q. Do, Paola Tarchi, Deborah Bonazza, Cristina Bottin, Loraine Kay D. Cabral, Long D. C. Tran, Thao P. T. Doan, Lory S. Crocè, Hoa L. T. Pham, Claudio Tiribelli, Caecilia H. C. Sukowati
Cells.2020; 9(12): 2672. CrossRef
Histological architectural classification determines recurrence pattern and prognosis after curative hepatectomy in patients with hepatocellular carcinoma
Hirohisa Okabe, Tomoharu Yoshizumi, Yo-ichi Yamashita, Katsunori Imai, Hiromitsu Hayashi, Shigeki Nakagawa, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Toru Beppu, Shinichi Aishima, Ken Shirabe, Hideo Baba, Yoshihiko Maehara, Motoyuki
PLOS ONE.2018; 13(9): e0203856. CrossRef
Overexpression of epithelial cell adhesion molecule as a predictor of poor outcome in patients with hepatocellular carcinoma
Chih‑Jan Ko, Chia‑Jung Li, Meng‑Yu Wu, Pei‑Yi Chu
Experimental and Therapeutic Medicine.2018;[Epub] CrossRef
Clinicopathologic Significance of Survivin Expression in Relation to CD133 Expression in Surgically Resected Stage II or III Colorectal Cancer
Wanlu Li, Mi-Ra Lee, EunHee Choi, Mee-Yon Cho
Journal of Pathology and Translational Medicine.2017; 51(1): 17. CrossRef
PIN1 in hepatocellular carcinoma is associated with TP53 gene status
Jun Sang Bae, Sang Jae Noh, Kyoung Min Kim, Kyu Yun Jang, Ho Sung Park, Myoung Ja Chung, Byung-Hyun Park, Woo Sung Moon
Oncology Reports.2016; 36(4): 2405. CrossRef

Differential Features of Microsatellite-Unstable Colorectal Carcinomas Depending on EPCAM Expression Status: Jung Ho Kim, Jeong Mo Bae, Kyung-Ju Kim, Ye-Young Rhee, Younghoon Kim, Nam-Yun Cho, Hye Seung Lee, Mee Soo Chang, Gyeong Hoon Kang; Korean J Pathol. 2014;48(4):276-282. Published online August 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.4.276

10,469 View
58 Download
15 Crossref

Abstract PDF

Background

Recent studies have revealed that a small subset of Lynch syndrome-associated colorectal carcinomas (CRCs) is caused by a germline EPCAM deletion-induced MSH2 epimutation. Based on the finding of this genetic alteration, we investigated the implications of EPCAM expression changes in microsatellite instability-high (MSI-H) CRCs.

Methods

Expression of EPCAM and DNA mismatch repair proteins was assessed by immunohistochemistry in 168 MSI-H CRCs. Using DNA samples of these tumors, MLH1 promoter methylation status was also determined by methylation-specific real-time polymerase chain reaction method (MethyLight).

Results

Among 168 MSI-H CRCs, complete loss (CL) and focal loss (FL) of EPCAM expression was observed in two (1.2%) and 22 (13.1%) cases, respectively. Both of the EPCAM-CL cases were found in MSH2-negative tumors without MLH1 promoter methylation. However, only nine of the 22 EPCAM-FL tumors had MSH2 deficiency. Of the 22 EPCAM-FL tumors, 13 showed MLH1 loss, and among them, nine cases were determined to have MLH1 methylation. EPCAM-FL was significantly associated with advanced stage (p=.043), distant metastasis (p=.003), poor differentiation (p=.001), and signet ring cell component (p=.004).

Conclusions

Loss of EPCAM expression is differentially associated with clinicopathological and molecular features, depending on the completeness of the loss, in MSI-H CRCs.

Citations

Citations to this article as recorded by

Unraveling the multifaceted role of EpCAM in colorectal cancer: an integrated review of its function and interplay with non-coding RNAs
Xingyu Jiang, Sumeng Wang, Qi Liang, Yiqian Liu, Lingxiang Liu
Medical Oncology.2023;[Epub] CrossRef
Outcomes of Definitive Treatment of Signet Ring Cell Carcinoma of the Rectum: Is Minimal Invasive Surgery Detrimental in Signet Ring Rectal Cancers?
S. Raghavan, Deepak Kumar Singh, J. Rohila, A. DeSouza, R. Engineer, A. Ramaswamy, V. Ostwal, A. Saklani
Indian Journal of Surgical Oncology.2020; 11(4): 597. CrossRef
Evaluation of the Role of Circulating Tumor Cells and Microsatellite Instability Status in Predicting Outcome of Advanced CRC Patients
Ippokratis Messaritakis, Maria Sfakianaki, Konstantinos Vogiatzoglou, Asimina Koulouridi, Chara Koutoulaki, Dimitrios Mavroudis, Maria Tzardi, Nikolaos Gouvas, John Tsiaoussis, John Souglakos
Journal of Personalized Medicine.2020; 10(4): 235. CrossRef
Is Ep-CAM Expression a Diagnostic and Prognostic Biomarker for Colorectal Cancer? A Systematic Meta-Analysis
Susu Han, Shaoqi Zong, Qi Shi, Hongjia Li, Shanshan Liu, Wei Yang, Wen Li, Fenggang Hou
EBioMedicine.2017; 20: 61. CrossRef
Prognostic factors in sporadic colon cancer with high-level microsatellite instability
Bo Young Oh, Jung Wook Huh, Yoon Ah Park, Yong Beom Cho, Seong Hyeon Yun, Hee Cheol Kim, Woo Yong Lee, Ho-Kyung Chun
Surgery.2016; 159(5): 1372. CrossRef
Clinical significance of fibroblast growth factor receptor 2 expression in patients with residual rectal cancer after preoperative chemoradiotherapy: relationship with KRAS or BRAF mutations and MSI status
Ghilsuk Yoon, Hwayoung Lee, Jae-Hoon Kim, Keun Hur, An Na Seo
Tumor Biology.2016; 37(8): 10209. CrossRef
Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis
Raj Thani Somasundaram, Jatinder Kaur, Iona Leong, Christina MacMillan, Ian J. Witterick, Paul G. Walfish, Ranju Ralhan
BMC Cancer.2016;[Epub] CrossRef
BRAF, PIK3CA, and HER2 Oncogenic Alterations According to KRAS Mutation Status in Advanced Colorectal Cancers with Distant Metastasis
Soo Kyung Nam, Sumi Yun, Jiwon Koh, Yoonjin Kwak, An Na Seo, Kyoung Un Park, Duck-Woo Kim, Sung-Bum Kang, Woo Ho Kim, Hye Seung Lee, Wayne A Phillips
PLOS ONE.2016; 11(3): e0151865. CrossRef
Twist1-induced epithelial-mesenchymal transition according to microsatellite instability status in colon cancer cells
Bo Young Oh, So-Young Kim, Yeo Song Lee, Hye Kyung Hong, Tae Won Kim, Seok Hyung Kim, Woo Yong Lee, Yong Beom Cho
Oncotarget.2016; 7(35): 57066. CrossRef
Clinicopathologic, molecular, and prognostic implications of the loss of EPCAM expression in colorectal carcinoma
Jung Ho Kim, Jeong Mo Bae, Young Seok Song, Nam-Yun Cho, Hye Seung Lee, Gyeong Hoon Kang
Oncotarget.2016; 7(12): 13372. CrossRef
Pathologic Factors Associated with Prognosis after Adjuvant Chemotherapy in Stage II/III Microsatellite-Unstable Colorectal Cancers
Jung Ho Kim, Jeong Mo Bae, Hyeon Jeong Oh, Hye Seung Lee, Gyeong Hoon Kang
Journal of Pathology and Translational Medicine.2015; 49(2): 118. CrossRef
HER3 protein expression in relation to HER2 positivity in patients with primary colorectal cancer: clinical relevance and prognostic value
An Na Seo, Yoonjin Kwak, Woo Ho Kim, Duck-Woo Kim, Sung-Bum Kang, Gheeyoung Choe, Hye Seung Lee
Virchows Archiv.2015; 466(6): 645. CrossRef
Clinical and prognostic value of MET gene copy number gain and chromosome 7 polysomy in primary colorectal cancer patients
An Na Seo, Kyoung Un Park, Gheeyoung Choe, Woo Ho Kim, Duck-Woo Kim, Sung-Bum Kang, Hye Seung Lee
Tumor Biology.2015; 36(12): 9813. CrossRef
c-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients with Colorectal Cancer
Kyu Sang Lee, Yoonjin Kwak, Kyung Han Nam, Duck-Woo Kim, Sung-Bum Kang, Gheeyoung Choe, Woo Ho Kim, Hye Seung Lee, Andreas Krieg
PLOS ONE.2015; 10(10): e0139727. CrossRef
Nuclear Ep-ICD accumulation predicts aggressive clinical course in early stage breast cancer patients
Gunjan Srivastava, Jasmeet Assi, Lawrence Kashat, Ajay Matta, Martin Chang, Paul G Walfish, Ranju Ralhan
BMC Cancer.2014;[Epub] CrossRef

First
Prev
Page of 1
Next
Last

Search