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

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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

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Recent Progress in Systemic Therapy for Advanced Hepatocellular Carcinoma
Narayanan Sadagopan, Aiwu Ruth He
International Journal of Molecular Sciences.2024; 25(2): 1259. CrossRef
Diagnostic value of expressions of cancer stem cell markers for adverse outcomes of hepatocellular carcinoma and their associations with prognosis: A Bayesian network meta‑analysis
Zhengrong Ou, Shoushuo Fu, Jian Yi, Jingxuan Huang, Weidong Zhu
Oncology Letters.2024;[Epub] 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
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Napabucasin Reduces Cancer Stem Cell Characteristics in Hepatocellular Carcinoma
Ya Li, Qiuju Han, Huajun Zhao, Quanjuan Guo, Jian Zhang
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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
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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
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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

Expression of CHOP in Squamous Tumor of the Uterine Cervix: Hyun Hee Chu, Jun Sang Bae, Kyoung Min Kim, Ho Sung Park, Dong Hyu Cho, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee, Myoung Ja Chung; Korean J Pathol. 2012;46(5):463-469. Published online October 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.5.463

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Abstract PDF

Background

High-risk human papillomavirus (HR-HPV) infection and abnormal p53 expression are closely involved in carcinogenesis of squamous cell carcinoma (SqCC) of uterine cervix. Recent studies have suggested that virus-induced endoplasmic reticulum (ER) stress modulates various cell survival and cell death signaling pathways. The C/EBP homologous protein (CHOP) is associated with ER stress-mediated apoptosis and is also involved in carcinogenesis of several human cancers. We hypothesized that CHOP is involved in the carcinogenesis of uterine cervical cancer in association with HR-HPV and/or p53.

Methods

Immunohistochemistry was used to analyze CHOP and p53 protein expression of tissue sections from 191 patients with invasive cancer or preinvasive lesions of the uterine cervix (61 cases of SqCC, 66 cases of cervical intraepithelial neoplasia [CIN] III, and 64 cases of CIN I).

Results

CHOP was expressed in 59.4% of CIN I, 48.5% of CIN III, and 70.5% of SqCC cases. It was also significantly more frequent in invasive SqCC than in preinvasive lesions (p=0.042). Moreover, CHOP expression significantly correlated with HR-HPV infection and p53 expression (p=0.009 and p=0.038, respectively).

Conclusions

Our results suggest that CHOP is involved in the carcinogenesis of the uterine cervix SqCC via association with HR-HPV and p53.

Citations

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Expression of GRP78 and its copartners in HEK293 and pancreatic cancer cell lines (BxPC-3/PANC-1) exposed to MRI and CT contrast agents
Ali Ahmed Azzawri, Ibrahim Halil Yildirim, Zeynep Yegin, Abdurrahim Dusak
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Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology
Elif Guzel, Sefa Arlier, Ozlem Guzeloglu-Kayisli, Mehmet Tabak, Tugba Ekiz, Nihan Semerci, Kellie Larsen, Frederick Schatz, Charles Lockwood, Umit Kayisli
International Journal of Molecular Sciences.2017; 18(4): 792. CrossRef
Endoplasmic reticulum stress pathway PERK‐eIF2α confers radioresistance in oropharyngeal carcinoma by activating NF‐κB
Qiao Qiao, Chaonan Sun, Chuyang Han, Ning Han, Miao Zhang, Guang Li
Cancer Science.2017; 108(7): 1421. CrossRef
Curcumin induces ER stress-mediated apoptosis through selective generation of reactive oxygen species in cervical cancer cells
Boyun Kim, Hee Seung Kim, Eun-Ji Jung, Jung Yun Lee, Benjamin K. Tsang, Jeong Mook Lim, Yong Sang Song
Molecular Carcinogenesis.2016; 55(5): 918. CrossRef
Down-regulation of C/EBP homologous protein (CHOP) expression in gastric cardia adenocarcinoma: Their relationship with clinicopathological parameters and prognostic significance
Xiao-Juan Zhu, She-Gan Gao, San-Qiang Li, Zhen-Guo Shi, Zhi-Kun Ma, Shan-Shan Zhu, Xiao-Shan Feng
Clinics and Research in Hepatology and Gastroenterology.2015; 39(3): 391. CrossRef
MG289 in <i>Mycoplasma genitalium</i> Enhances Microbial Invasion and Bacterial Persistence in Benign Human Prostate Cells
Wasia Rizwani, Leticia Reyes, Jeongsoon Kim, Steve Goodison, Charles J. Rosser
Open Journal of Urology.2013; 03(06): 232. CrossRef

Expression of Cortactin and Focal Adhesion Kinase in Colorectal Adenocarcinoma: Correlation with Clinicopathologic Parameters and Their Prognostic Implication: Yo Na Kim, Ji Eun Choi, Jun Sang Bae, Kyu Yun Jang, Myoung Ja Chung, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee, Ho Sung Park; Korean J Pathol. 2012;46(5):454-462. Published online October 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.5.454

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Abstract PDF

Background

Cortactin and focal adhesion kinase (FAK) are two important components among actin cross-linking proteins that play a central role in cell migration.

Methods

The aims of this study were to evaluate the expression of cortactin and FAK in normal colorectal mucosa and colorectal adenocarcinoma (CRC) using tissue microarray of 2 mm cores to correlate their expression with other clinicopathological factors and, investigate their prognostic significance.

Results

Twenty (9%) and 24 cases (11%) of normal colorectal mucosa were immunoreactive for cortactin and FAK. In addition, 184 (84%) and 133 cases (61%) of CRCs were immunoreactive for cortactin and FAK, respectively. Cortactin expression was associated with histologic differentiation and FAK expression. Cortactin, but not FAK expression was also correlated with poor overall and relapse-free survival and served well as an independent prognostic factor for poor survival.

Conclusions

Cortactin expression, in association with FAK expression, may plays an important role in tumor progression. Furthermore, it may also be a satisfactory biomarker to predict tumor progression and survival in CRC patients.

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Lik Hang Lee, Lindy Davis, Lourdes Ylagan, Angela R Omilian, Kristopher Attwood, Canan Firat, Jinru Shia, Philip B Paty, William G Cance
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PZR promotes metastasis of colorectal cancer through increasing FAK and Src phosphorylation
Dan Tan, Wenpeng Zhang, Yu Tao, Yesseyeva Galiya, Mingliang Wang
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Overexpression and Tyr421-phosphorylation of cortactin is induced by three-dimensional spheroid culturing and contributes to migration and invasion of pancreatic ductal adenocarcinoma (PDAC) cells
Katharina Stock, Rebekka Borrink, Jan-Henrik Mikesch, Anna Hansmeier, Jan Rehkämper, Marcel Trautmann, Eva Wardelmann, Wolfgang Hartmann, Jan Sperveslage, Konrad Steinestel
Cancer Cell International.2019;[Epub] CrossRef
Cortactin promotes colorectal cancer cell proliferation by activating the EGFR-MAPK pathway
Xiaojian Zhang, Kun Liu, Tao Zhang, Zhenlei Wang, Xuan Qin, Xiaoqian Jing, Haoxuan Wu, Xiaopin Ji, Yonggang He, Ren Zhao
Oncotarget.2017; 8(1): 1541. CrossRef
Prognostic Value of Focal Adhesion Kinase (FAK) in Human Solid Carcinomas: A Meta-Analysis
Xiao-Qing Zeng, Na Li, Li-Li Ma, Yu-Jen Tseng, Nai-Qing Zhao, Shi-Yao Chen, Han-Chung Wu
PLOS ONE.2016; 11(9): e0162666. CrossRef
Regulators of Actin Dynamics in Gastrointestinal Tract Tumors
Konrad Steinestel, Eva Wardelmann, Wolfgang Hartmann, Inga Grünewald
Gastroenterology Research and Practice.2015; 2015: 1. CrossRef

Expressions of E-cadherin, Cortactin and MMP-9 in Pseudoepitheliomatous Hyperplasia and Squamous Cell Carcinoma of the Head and Neck: Their Relationships with Clinicopathologic Factors and Prognostic Implication: Tack Kune You, Kyoung Min Kim, Sang Jae Noh, Jun Sang Bae, Kyu Yun Jang, Myoung Ja Chung, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee, Ho Sung Park; Korean J Pathol. 2012;46(4):331-340. Published online August 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.331

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Abstract PDF

Background

E-cadherin, cortactin, and matrix metalloproteinase (MMP)-9 have roles in tumor development or progression, but their expression has not been fully investigated in pseudoepitheliomatous hyperplasia (PEH) and squamous cell carcinoma (SCC) of the head and neck.

Methods

We evaluated the immunohistochemical expression of E-cadherin, cortactin, and MMP-9 in 29 cases of PEH and 97 cases of SCC. Additionally, we evaluated their relationship with clinicopathologic factors and prognostic implications in SCC.

Results

Thirty-five cases of SCC showed reduced expression of E-cadherin, whereas none of the PEH did. A total of 20 cases and 11 cases of SCC were immunoreactive for cortactin and MMP-9, respectively, whereas none of the PEH did. In SCC, reduced expression of E-cadherin was correlated with cortactin expression and invasion depth. Cortactin expression was correlated with differentiation, T classification, and recurrence and/or metastasis. MMP-9 expression was correlated with invasion depth. Cortactin expression was correlated with poor overall survival and relapse-free survival and it was an independent prognostic factor.

Conclusions

The reduced expression of E-cadherin and the expression of cortactin may be helpful for the differential diagnosis of PEH and SCC. Furthermore, cortactin expression in association with reduced E-cadherin expression is correlated with poor prognosis in SCC.

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