Journal of Pathology and Translational Medicine

Original Articles

The Role of TWIST in Ovarian Epithelial Cancers: Kyungbin Kim, Eun Young Park, Man Soo Yoon, Dong Soo Suh, Ki Hyung Kim, Jeong Hee Lee, Dong Hoon Shin, Jee Yeon Kim, Mee Young Sol, Kyung Un Choi; Korean J Pathol. 2014;48(4):283-291. Published online August 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.4.283

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Background

Epithelial-mesenchymal transition (EMT) is associated with tumor hypoxia. EMT is regulated, in part, by the action of TWIST, which inhibits of E-cadherin expression and may interfere with the p53 tumor-suppressor pathway.

Methods

We examined the expression of TWIST, E-cadherin, hypoxia-inducible factor 1α (HIF1α), and p53 by immunohistochemistry in 123 cases of ovarian epithelial cancers (OEC) to evaluate the role of TWIST in OEC. We assessed the association between protein expression and clinicopathologic parameters.

Results

The expression of TWIST, E-cadherin, HIF1α, and p53 proteins was found in 28.5%, 51.2%, 35.0%, and 29.3% of cases, respectively. TWIST expression was associated with higher histologic grade and unfavorable survival. TWIST expression was correlated with HIF1α expression and reduced E-cadherin expression. The altered HIF1α/TWIST/E-cadherin pathway was associated with lower overall survival (OS), while the co-expression of TWIST and p53 was correlated with lower progression-free survival. In the multivariate analyses, TWIST expression was an independent prognostic factor for OS.

Conclusions

Our data imply that TWIST expression could be a useful predictor of unfavorable prognosis for OEC. TWIST may affect the p53 tumor-suppressor pathway. Moreover, hypoxia-mediated EMT, which involves the HIF1α/TWIST/E-cadherin pathway may play an important role in the progression of OEC.

Citations

Citations to this article as recorded by

E-Cadherin Expression in Relation to Clinicopathological Parameters and Survival of Patients with Epithelial Ovarian Cancer
Michal Kielbik, Izabela Szulc-Kielbik, Magdalena Klink
International Journal of Molecular Sciences.2022; 23(22): 14383. CrossRef
Oxygen sensing, mitochondrial biology and experimental therapeutics for pulmonary hypertension and cancer
Danchen Wu, Asish Dasgupta, Austin D. Read, Rachel E.T. Bentley, Mehras Motamed, Kuang-Hueih Chen, Ruaa Al-Qazazi, Jeffrey D. Mewburn, Kimberly J. Dunham-Snary, Elahe Alizadeh, Lian Tian, Stephen L. Archer
Free Radical Biology and Medicine.2021; 170: 150. CrossRef
Hypoxia-Induced Epithelial-Mesenchymal Transition in Cancers: HIF-1α and Beyond
Shing Yau Tam, Vincent W. C. Wu, Helen K. W. Law
Frontiers in Oncology.2020;[Epub] CrossRef
Expression of selected epithelial–mesenchymal transition transcription factors in serous borderline ovarian tumors and type I ovarian cancers
Pawel Sadlecki, Jakub Jóźwicki, Paulina Antosik, Marek Grabiec
Tumor Biology.2018; 40(6): 101042831878480. CrossRef
Expression and prognostic significance of epithelial-mesenchymal transition-related markers and phenotype in serous ovarian cancer
In Hye Song, Kyu-Rae Kim, Sehun Lim, Seok-Hyung Kim, Chang Ohk Sung
Pathology - Research and Practice.2018; 214(10): 1564. CrossRef
Transcription factors controlling E-cadherin down-regulation in ovarian cancer
Holly Russell, Md Zahidul Islam Pranjol
Bioscience Horizons: The International Journal of Student Research.2018;[Epub] CrossRef
Immunohistochemical expression of TWIST in oral squamous cell carcinoma and its correlation with clinicopathologic factors
Maryam Seyedmajidi, Safoura Seifi, Dariush Moslemi, Seyyedeh-Fatemeh Mozaffari, Hemmat Gholinia, Zahra Zolfaghari
Journal of Cancer Research and Therapeutics.2018; 14(5): 964. CrossRef
Activation of TWIST1 by COL11A1 promotes chemoresistance and inhibits apoptosis in ovarian cancer cells by modulating NF‐κB‐mediated IKKβ expression
Yi‐Hui Wu, Yu‐Fang Huang, Tzu‐Hao Chang, Cheng‐Yang Chou
International Journal of Cancer.2017; 141(11): 2305. CrossRef
MicroRNA-219-5p inhibits the proliferation, migration, and invasion of epithelial ovarian cancer cells by targeting the Twist/Wnt/β-catenin signaling pathway
Chunyan Wei, Xi Zhang, Sai He, Bianli Liu, Hongfang Han, Xuejun Sun
Gene.2017; 637: 25. CrossRef
Inhibition of proliferation and invasion of hepatocellular carcinoma cells by lncRNA-ASLNC02525 silencing and the mechanism
Zi Chen, Dongwen Xu, Tao Zhang
International Journal of Oncology.2017; 51(3): 851. CrossRef
Is overexpression of TWIST, a transcriptional factor, a prognostic biomarker of head and neck carcinoma? Evidence from fifteen studies
Xianlu Zhuo, Huanli Luo, Aoshuang Chang, Dairong Li, Houyu Zhao, Qi Zhou
Scientific Reports.2015;[Epub] CrossRef

The Clinicopathological Significance of Epithelial Mesenchymal Transition Associated Protein Expression in Head and Neck Squamous Cell Carcinoma: Kyu Ho Kim, Lucia Kim, Suk Jin Choi, Jee Young Han, Joon Mee Kim, Young Chae Chu, Young-Mo Kim, In Suh Park, Joo Han Lim; Korean J Pathol. 2014;48(4):263-269. Published online August 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.4.263

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Abstract PDF

Background

Epithelial mesenchymal transition (EMT) has an important role in invasion and metastasis of tumor cells. The purpose of this study was to evaluate the roles of EMT-associated proteins on progression and metastasis as a prognostic/predictive factor in curatively-resected (R0) head and neck squamous cell carcinoma (HNSCC).

Methods

A total of 118 patients who received curative surgery for HNSCC at Inha University Hospital between January 1996 and December 2011 were included. We used protein immunohistochemistry to evaluate the expression of E-cadherin, vimentin, and EZH2 on tissue microarrays. Also, we reviewed all medical records and analyzed the relationship between the expression of EMT-associated proteins and prognosis.

Results

The E-cadherin-negative group showed more moderate/poor differentiation of cancer cell type than the higher E-cadherin-expressing group (p=.016) and high EZH2 expression was significantly correlated with nodal metastasis (p=.012). Our results demonstrate a significant association between high expression of EZH2 and vimentin and presence of distant progression (p=.026). However, expression of E-cadherin, vimentin, and EZH2 was not significantly associated with overall survival.

Conclusions

These findings suggest that an EMT-associated protein expression profile is correlated with aggressiveness of disease and prognosis, and could be a useful marker for determination of additional treatment in curatively-resected HNSCC patients.

Citations

Citations to this article as recorded by

Polycomb repressive complex 2 and its core component EZH2: potential targeted therapeutic strategies for head and neck squamous cell carcinoma
Yuxi Cheng, Zhengzheng Song, Xiaodan Fang, Zhangui Tang
Clinical Epigenetics.2024;[Epub] CrossRef
Prognostic Value of TWIST1 and EZH2 Expression in Colon Cancer
Samar M. Abdel Raouf, Taiseer R. Ibrahim, Lobna A. Abdelaziz, Mohamed I. Farid, Salem Y Mohamed
Journal of Gastrointestinal Cancer.2021; 52(1): 90. CrossRef
HOXB5 acts as an oncogenic driver in head and neck squamous cell carcinoma via EGFR/Akt/Wnt/β-catenin signaling axis
Kyungmin Lee, Jae Won Chang, Chan Oh, Lihua Liu, Seung-Nam Jung, Ho-Ryun Won, Young Il Kim, Ki-Sang Rha, Bon Seok Koo
European Journal of Surgical Oncology.2020; 46(6): 1066. CrossRef
EZH2 overexpression in head and neck cancer is related to lymph node metastasis
Julie C. Nienstedt, Cornelia Schroeder, Till Clauditz, Ronald Simon, Guido Sauter, Adrian Muenscher, Marco Blessmann, Henning Hanken, Christina Pflug
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Lizandra Jimenez, Jihyeon Lim, Berta Burd, Thomas M. Harris, Thomas J. Ow, Nicole Kawachi, Thomas J. Belbin, Ruth Angeletti, Michael B. Prystowsky, Geoffrey Childs, Jeffrey E. Segall
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Xiaobing Liu, Qingjian Wu, Longkun Li
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Shanshan Sun, Feng Yu, Lun Zhang, Xuan Zhou
Cellular Signalling.2016; 28(5): 481. CrossRef
High EZH2 Protein Expression Is Associated with Poor Overall Survival in Patients with Luminal A Breast Cancer
Si-Hyong Jang, Jong Eun Lee, Mee-Hye Oh, Ji-Hye Lee, Hyun Deuk Cho, Kyung-Ju Kim, Sung Yong Kim, Sun Wook Han, Han Jo Kim, Sang Byung Bae, Hyun Ju Lee
Journal of Breast Cancer.2016; 19(1): 53. CrossRef
EZH2 promotes invasion and metastasis of laryngeal squamous cells carcinoma via epithelial-mesenchymal transition through H3K27me3
HuaNan Luo, Yuan Jiang, SiJing Ma, HuanHuan Chang, ChunXi Yi, Hui Cao, Ying Gao, HaiLi Guo, Jin Hou, Jing Yan, Ying Sheng, XiaoYong Ren
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Loss of E-cadherin and Acquisition of Vimentin in Epithelial-Mesenchymal Transition are Noble Indicators of Uterine Cervix Cancer Progression: Na-Hye Myong; Korean J Pathol. 2012;46(4):341-348. Published online August 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.341

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Abstract PDF

Background

Epithelial-mesenchymal transition (EMT) has been known to play a key role in the stromal invasion of carcinoma in situ (CIS) lesion. Loss of E-cadherin and acquisition of vimentin are two critical steps in EMT, that are induced by Snail-1 upregulation associated with overexpression of epidermal growth factor receptor (EGFR). However, roles of EMT-related proteins in human cervical tissues have not been fully elucidated. In this study, we investigated the immunoexpressions of EMT-related proteins in CIS, microinvasive squamous cell carcinoma (SCC), and invasive SCC to demonstrate their key roles in tumor progression.

Methods

Eighty one CIS, 17 microinvasive, and 21 invasive SCC cases were immunostained with primary antibodies for Snail-1, EGFR, E-cadherin, and vimentin on paraffin-embedded tissue microarray blocks.

Results

EGFR and Snail-1 proteins were highly expressed but the levels were not significantly different between the three groups. However, loss of E-cadherin and acquisition of vimentin were proven to occur significantly higher in microinvasive and invasive SCC cases than in CIS.

Conclusions

E-cadherin and vimentin were found to be two useful indicators of EMT in evaluating stromal invasion of CIS. However, it was not demonstrated for Snail-1 and EGFR proteins to play any key role in the progression of cervix cancer.

Citations

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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.

Citations

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p16INK4a, PTEN, E-cadherin, Bcl-2 and Ki-67 Expression in Prostate Cancer: Its Relationship with the Metastatic Potential and Known Prognostic Factors.: Seok Ju Park, Woo Jung Sung, Mi Jin Kim; Korean J Pathol. 2010;44(6):597-604.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.597

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Abstract PDF

BACKGROUND
At present, adequate prognostic markers for prostate cancer progression are still lacking, in spite of intensive investigation. Accordingly, our study examined the relationship between expression of candidate biomarkers and metastasis in prostate cancer patients. Correlation of molecular markers with prostate-specific antigen (PSA) level, Gleason sum score and tumor stage were also evaluated.
METHODS
A total of 105 prostate tumor specimens and specimens from 19 cases of nodular hyperplasia were obtained through Yeungnam University Hospital from 2007 to 2008. Immunohistochemical analyses for p16INK4a, phosphatase and tensin homolog (PTEN), E-cadherin, Ki-67 and Bcl-2 were performed.
RESULTS
Overexpression of Bcl-2 was significantly related to bone (p = 0.006) and nodal metastases (p = 0.017). Other biomarkers were not related to metastatic potential. There were statistically significant relationships between increased PSA level and loss of expression of PTEN (p = 0.019) and E-cadherin (p = 0.001). High Ki-67 index was significantly correlated with nodal metastasis (p = 0.029) as well as with loss of p16INK4a expression (p = 0.002) and high Gleason score (p = 0.011).
CONCLUSIONS
High Gleason score, Bcl-2 overexpression and increased Ki-67 labeling have significant predictive value in assessing the potential for prostate cancer metastasis. In addition, a high Ki-67 index is related to high Gleason score and loss of p16INK4a expression.

Citations

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beta-Catenin Expression in Gastric Carcinogenesis.: Haeyoun Kang, Yon Rak Choi, Hoguen Kim; Korean J Pathol. 2001;35(5):376-382.

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Abstract PDF: BACKGROUND
The molecular pathogenesis of gastric carcinoma is not yet well characterized. The purpose of this study is to assess the role of beta-catenin in gastric carcinogenesis.
METHODS
We analyzed beta-catenin expression using immunohistochemistry on 68 gastric adenomas and 34 gastric adenocarcinomas, and compared the result with pathological and molecular types of tumors and E-cadherin expression.
RESULTS
Nuclear expression of beta-catenin was noted more frequently in gastric adenomas than in carcinomas (40% vs. 21%, 0.05< or = P<1). There was no significant relationship between nuclear beta-catenin expression and histologic degree of adenoma, histologic type of carcinoma or microsatellite instability. E-cadherin expression showed significantly more frequent decrease in the membrane stainability of carcinomas compared to adenomas (P<0.01).
CONCLUSIONS
The frequent nuclear beta-catenin expression in gastric adenomas suggests that the beta-catenin alteration might play an early role in gastric carcinogenesis.

E-cadherin Expression in Distinguishing Ductal and Lobular Carcinomas of the Breast.: Eun Deok Chang, An Hi Lee, Eun Jung Lee, Seok Jin Kang, Chang Suk Kang; Korean J Pathol. 2002;36(5):323-327.

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Abstract PDF: BACKGROUND
Most breast carcinomas are easily categorized as ductal or lobular. However, in some cases the distinction can be difficult since some tumors may have intermediate features of these two. Prior studies suggest that E-cadherin is useful to classify tumors as ductal or lobular, as it is lost in lobular but not in ductal carcinomas.
METHODS
We studied the histologic features and E-cadherin expression by immunohistochemistry in 57 cases of breast carcinomas, which were divided into three groups based on histology. Group 1 included 4 cases of infiltrating lobular carcinoma (IFL) and 1 case of lobular carcinoma in situ (LCIS) (n=5). Group 2 included infiltrating ductal carcinoma (IFD) with some features of IFL (n=48). Group 3 included a solid type of intraductal carcinoma (DCIS) (n=4). E-cadherin staining was scored as negative or positive.
RESULTS
All 5 cases from group 1 were E-cadherin negative, and all 4 DCIS cases were positive. Only 2 (0.04%) of the 48 cases from group 2 were E-cadherin negative.
CONCLUSIONS
Our findings suggest that the majority of cases with morphologically IFD with some IFL features are ductal. E-cadherin immunostaining is of value in helping to characterize breast carcinomas with indeterminate morphologic features.

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