Cancer Research and Treatment

Original Articles

Clinical Significance of Protein Expression of Cyclooxygenase-2 and Somatostatin Receptors in Gastroenteropancreatic Neuroendocrine Tumors: Hee Sung Kim, Hye Seung Lee, Woo Ho Kim; Cancer Res Treat. 2011;43(3):181-188. Published online September 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.3.181

PURPOSE
This study was undertaken to evaluate the significance of cyclooxygenase-2 (COX2) overexpression and the expression of somatostatin receptor (SSTR) subtypes in gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
MATERIALS AND METHODS
Two hundred and forty-seven cases of GEP-NET, comprising 86 foregut and 156 hindgut primary NETs, and 5 metastatic NETs in the liver, were studied retrospectively with immunohistochemistry for COX2, chromogranin A, Ki-67, SSTR1, SSTR2, and SSTR5.
RESULTS
COX2 overexpression was observed in 54%(126 of 234), and SSTR1, SSTR2, and SSTR5 positivity in 84%(196 of 233), 72%(168 of 233), and 55%(128 of 232), respectively. COX2 overexpression was found to be positively correlated with Ki-67 labeling index and inversely correlated with the expression of SSTR subtypes. In addition, the expression of SSTR subtypes was tightly correlated in any comparative pairs. A significant inverse correlation was found between COX2 and SSTR2 expression in the foregut, but not hindgut NETs. Kaplan-Meier analyses showed that COX2 overexpression (p=0.003) and high Ki-67 labeling index (p<0.001) were associated with poor overall survival (OS), whereas expression of SSTR2 (p<0.001) was associated with better OS of GEP-NET patients. Multivariate analysis revealed negative SSTR2 expression as an independent prognostic marker in GEP-NET patients (p<0.001).
CONCLUSION
Our results suggest that expression of SSTR subtypes is associated with favorable prognosis, whereas COX2 overexpression is associated with poor prognosis in GEP-NETs. Taken together, COX2 could be a possible therapeutic target in some subsets of GEP-NETs.

Citations

Citations to this article as recorded by

Crosstalk of TGF-β and somatostatin signaling in adenocarcinoma and neuroendocrine tumors of the pancreas: a brief review
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Frontiers in Endocrinology.2025;[Epub] CrossRef
A Clinicopathological Analysis of Asian Patients with Adrenocortical Carcinoma: A Single-Center Experience
Wen-Hsuan Tsai, Shuen-Han Dai, Chun-Chuan Lee, Ming-Nan Chien, Yi-Hong Zeng
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Philippe Brunner, Ann-Catherine Jörg, Katharina Glatz, Lukas Bubendorf, Piotr Radojewski, Maria Umlauft, Nicolas Marincek, Petar-Marko Spanjol, Thomas Krause, Rebecca A. Dumont, Helmut R. Maecke, Jan Müller-Brand, Matthias Briel, Anja Schmitt, Aurel Perre
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Determination of Mammalian Target of Rapamycin Hyperactivation as Prognostic Factor in Well-Differentiated Neuroendocrine Tumors
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Small Cell Carcinomas of the Bladder Highly Express Somatostatin Receptor Type 2A
Nalan Neşe, Banu S. Kumbaraci, Dilek E. Baydar, Işin Kiliçaslan, Ayşegül A. Sari, Sait Şen, Ipek I. Gönül, Duygu Kankaya, Yasemin Özlük, Murat Ermete, Ayşim Özağari, Nebil Bal, Saba Kiremitçi, Kürşat Yildiz, Burçin Tuna, Nilay Şen, Kutsal Yörükoğlu
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Recent Updates on Neuroendocrine Tumors From the Gastrointestinal and Pancreatobiliary Tracts
Joo Young Kim, Seung-Mo Hong
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Kai Duan, Ozgur Mete
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Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors
Zhi Rong Qian, Tingting Li, Monica Ter-Minassian, Juhong Yang, Jennifer A. Chan, Lauren K. Brais, Yohei Masugi, Arunthathi Thiaglingam, Nichole Brooks, Reiko Nishihara, Mireille Bonnemarie, Atsuhiro Masuda, Kentaro Inamura, Sun A. Kim, Kosuke Mima, Yasuta
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Flávio L. L. SALGADO, Ricardo ARTIGIANI-NETO, Gaspar de Jesus LOPES-FILHO
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Cytoplasmic Expression of HuR is Related to Cyclooxygenase-2 Expression in Colon Cancer: Sung-Jig Lim, Suk-Hwan Lee, Sun Hyung Joo, Jeong Yoon Song, Sung Il Choi; Cancer Res Treat. 2009;41(2):87-92. Published online June 30, 2009; DOI: https://doi.org/10.4143/crt.2009.41.2.87

Abstract PDF PubReader ePub

Purpose

HuR, human family embryonic-lethal abnormal vision-like protein, can bind to mRNA and stabilizes the nucleic acid in the cytoplasm, resulting in more efficient translation. HuR is predominantly present in the nucleus and shuttles between the nucleus and cytoplasm. HuR stabilizes cyclooxygenase-2 (Cox-2) mRNA in several cancers, including breast, stomach, lung and brain cancer.

Materials and Methods

We investigated the expression and cellular location of HuR, as well as evaluated Cox-2 expression in 79 colorectal cancer patients with the use of immunohistochemical methods. The biological implications of HuR localization and Cox-2 expression in colorectal carcinoma were evaluated.

Results

Nuclear HuR expression was observed in 59 (74.7%) tumors and cytoplasmic HuR expression was seen in 25 (31.6%) tumors. Cox-2 immunoreactivity was noted in 42 (53%) tumors. The expression of cytoplasmic HuR was significantly associated with Cox-2 expression (p=0.004). Cytoplasmic expression of HuR showed a correlation with lymphatic invasion (p=0.025) and the presence of a lymph node metastasis (p=0.027). The presence of nuclear HuR showed no correlation with Cox-2 expression or any other of the clinicopathological parameters that were examined.

Conclusion

These results suggest that cytoplasmic translocation of HuR is associated with Cox-2 expression for some colorectal carcinomas.

Citations

Citations to this article as recorded by

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Expression of Cyclooxygenase-2 in Human Breast Cancer: Relationship with HER-2/neu and other Clinicopathological Prognostic Factors: Eunmi Nam, Soon Nam Lee, Seock-Ah Im, Do-Yeun Kim, Kyoung Eun Lee, Sun Hee Sung; Cancer Res Treat. 2005;37(3):165-170. Published online June 30, 2005; DOI: https://doi.org/10.4143/crt.2005.37.3.165

Abstract PDF PubReader ePub

Purpose

Previous epidemiologic studies have demonstrated that nonsteroidal anti-inflammatory drugs can reduce the risk of breast cancer, and this possibly happens via cyclooxygenase (COX) inhibition. Moreover, growth factor-inducible COX-2, which is overexpressed in neoplastic tissue, is an attractive therapeutic target. Thus, we evaluated the expression of COX-2 in breast cancer tissues, and we assessed the association between COX-2 expression and HER-2/neu expression and also with several clinicopathological features.

Materials and Methods

We analyzed the surgical specimens from 112 women with breast cancer who had undergone lumpectomy or mastectomy. The expressions of COX-2, HER-2/neu, MMP-2 and TIMP-2 were determined immunohistochemically. The correlations between COX-2 expression and several variables, including clinicopathological factors, HER-2/neu expression, MMP-2 expression and TIMP-2 expression were analyzed. Survival analysis was also performed with respect to COX-2 overexpression.

Results

The overexpression of COX-2 protein was observed in 28.6% of the breast cancer tissues. Tumors with lymph node metastasis more frequently showed COX-2 overexpression than did those tumors without metastasis (p=0.039), and the increased COX-2 expression correlated positively with HER-2/neu overexpression (p=0.000). No significant differences were found for the MMP-2 or TIMP-2 expression rates in the COX-2 positive and negative groups. The survival analysis revealed no significant differences according to the COX-2 expression.

Conclusion

This study results suggest that increased COX-2 expression is related with the progression of breast cancer, e.g., with lymph node invasion. COX-2 overexpression found to be related with HER-2/neu overexpression, but not with MMP-2 or TIMP-2 expression. These results support the potential use of selective agents that inhibit COX-2 or HER-2/neu for the management of breast cancer.

Citations

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Postoperative administration of ketorolac averts morphine-induced angiogenesis and metastasis in triple-negative breast cancer
Zhongqi Liu, Shi Cheng, Ganglan Fu, Fengtao Ji, Chengli Wang, Minghui Cao
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Molecular and Clinical Oncology.2017; 6(4): 494. CrossRef
Cyclooxygenase-2 Expression in Invasive Breast Carcinomas of No Special Type and Correlation with Pathological Profiles Suggest a Role in Tumorigenesis Rather than Cancer Progression
Nurul Akmar Misron, Lai-Meng Looi, Nik Raihan Nik Mustapha
Asian Pacific Journal of Cancer Prevention.2015; 16(4): 1553. CrossRef
Stromal, rather than epithelial cyclooxygenase-2 (COX-2) expression is associated with overall survival of breast cancer patients
Justyna Urban, Łukasz Kuźbicki, Grzegorz Szatkowski, Agata Stanek-Widera, Dariusz Lange, Barbara W Chwirot
BMC Cancer.2014;[Epub] CrossRef
Prognostic influence of cyclooxygenase-2 protein and mRNA expression in node-negative breast cancer patients
Isabel Sicking, Karlien Rommens, Marco J Battista, Daniel Böhm, Susanne Gebhard, Antje Lebrecht, Cristina Cotarelo, Gerald Hoffmann, Jan G Hengstler, Marcus Schmidt
BMC Cancer.2014;[Epub] CrossRef

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Clinical Value of Cyclooxygenase-2 Expression in Human Breast Carcinoma: Jin-Hee Ahn, Sung-Bae Kim, Sei-Hyun Ahn, Gyung-Yub Gong, Myung-Ju Ahn, Yoon-Koo Kang, Jung-Shin Lee, Woo Kun Kim; Cancer Res Treat. 2004;36(3):192-198. Published online June 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.3.192

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Purpose

To determine whether COX-2 expression is associated with clinicopathological parameters, including c-erb-B2 overexpression and angiogenesis, and the disease-free survival of patients with operable breast cancer.

Materials and Methods

Paraffin-embedded tissue samples were selected from 205 patients surgically resected for breast cancer, between 1991 and 1997, and followed-up for at least 4 years. Samples were immunohistochemically stained with antibodies to COX-2, c-erb-B2 and CD34.

Results

COX-2 and c-erb-B2 expressions were detected in 118/205 (57.6%) and 58/205 (28.3%) patients, respectively. COX-2 expression was significantly higher in c-erb-B2 positive than c-erb-B2 negative tumors (75.9% vs. 49.7%, p-value 0.001). COX-2 expression was positively correlated with microvessel count (13.3±8.0 vs. 6.6±7.0, p-value 0.050), but not with other clinicopathological characteristics, including tumor size, involved axil lary lymph nodes and estrogen or progesterone receptor status. Although COX-2 expression itself was not a prognostic marker, breast cancer patients with tumors that co-expressed both COX-2 and c-erb-B2 had a poorer 5-year disease-free survival rate than those that did not (60.2% vs. 78.3%, p-value 0.0527).

Conclusion

Our data suggest that COX-2 expression occurs frequently in c-erb-B2 positive breast cancer, and co-expression of COX-2 and c-erb-B2 may be a useful prognostic marker in patients with operable breast cancer.

Citations

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The Role of Immunohistochemical Biomarkers as Prognostic Factors by the Use of a Tissue Microarray in Breast Cancer Patients Under 45-years-old
Eun Seog Kim, Doo Ho Choi, So Young Jin, Dong Wha Lee, Hee Sook Park, Min Hyuk Lee, Jong Ho Won, Yong Ho Kim, Kyu Taek Lee, Sung Yong Kim
The Journal of the Korean Society for Therapeutic Radiology and Oncology.2008; 26(1): 45. CrossRef
Expression of Cyclooxygenase-2 in Human Breast Cancer: Relationship with HER-2/neu and other Clinicopathological Prognostic Factors
Eunmi Nam, Soon Nam Lee, Seock-Ah Im, Do-Yeun Kim, Kyoung Eun Lee, Sun Hee Sung
Cancer Research and Treatment.2005; 37(3): 165. CrossRef
Cyclooxygenase-2: A Potential Target in Human Cancer
Jong-Ho Won
Cancer Research and Treatment.2004; 36(3): 161. CrossRef

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Expression of Cyclooxygenase (COX)-2 as a Prognostic Factor in Nasopharyngeal Cancer: Kyubo Kim, Hong-Gyun Wu, Suk Won Park, Chong Jai Kim, Charn Il Park; Cancer Res Treat. 2004;36(3):187-191. Published online June 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.3.187

Abstract PDF PubReader ePub

Purpose

To evaluate the relationship between treatment failure and COX-2 expression in nasopharyngeal cancer patients treated with chemotherapy and radiotherapy.

Materials and Methods

The subjects of this study were 22 nasopharyngeal cancer patients. The patients were treated with neoadjuvant chemotherapy, followed by radiotherapy, or with radiotherapy alone. The formalin-fixed, paraffin-embedded tissues of 11 patients who developed a locoregional recurrence (n=7) or distant metastasis (n=4) were compared with those of 11 disease free patients. Prognostic factors, including histological type, stage, radiation dose and chemotherapy, were well balanced between the two groups. The COX-2 expression was determined immunohistochemically.

Results

COX-2 expression was stronger in the patients with a locoregional recurrence or distant metastasis than in those free of disease. The COX-2 distribution scores of the control group were as follows: 0 in 7, 1 in 2 and 2 in 2 patients. In the recurrence group, the scores were as follows; 0 in 3, 1 in 1, 2 in 2 and 3 in 5 patients. COX-2 expression was shown to have a statistically significant influence on the treatment failure by the Mann-Whitney U test (p=0.024) and Mantel-Haenszel Chi-Square test (p=0.018). It also significantly influenced the treatment failure when an analysis was performed within patients with a undifferentiated histology (p=0.039 by the Mann-Whitney U test, p=0.037 by the Mantel-Haenszel Chi-Square test).

Conclusion

COX-2 expression is believed to be one of the important factors associated with a locoregional recurrence or distant metastasis.

Citations

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Clinicopathological and prognostic significance of cyclooxygenase-2 expression in head and neck cancer: A meta-analysis
Bin Yang, Lin Jia, Qiaojuan Guo, Hui Ren, Yanping Hu, Tao Xie
Oncotarget.2016; 7(30): 47265. CrossRef
Prognostic significance of expression of cyclooxygenase‐2, vascular endothelial growth factor, and epidermal growth factor receptor in nasopharyngeal carcinoma
Jianji Pan, Tianlan Tang, Luying Xu, Jiade J. Lu, Senan Lin, Sufang Qiu, Gang Chen, Ivan W. K. Tham
Head & Neck.2013; 35(9): 1238. CrossRef
Immunohistochemical study identifying prognostic biomolecular markers in nasopharyngeal carcinoma treated by radiotherapy
Yeon‐Joo Kim, Heounjeong Go, Hong‐Gyun Wu, Yoon Kyung Jeon, Suk Won Park, Seung Hee Lee
Head & Neck.2011; 33(10): 1458. CrossRef
Immunohistochemical Study to Evaluate the Prognostic Significance of Four Biomolecular Markers in Radiotherapy of Nasopharyngeal Carcinoma
Yeon-Joo Kim, Seung Hee Lee, Hong-Gyun Wu, Heounjeong Go, Yoon Kyung Jeon
The Journal of the Korean Society for Therapeutic Radiology and Oncology.2010; 28(2): 57. CrossRef

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Expression of Cyclooxygenase-2 and Tumor Microvessel Density in Colorectal Cancer: Seoung Wan Chae, Jin Hee Sohn, Eo Jin Kim, Eun Yoon Cho, Bong Hwa Lee; Cancer Res Treat. 2003;35(5):400-406. Published online October 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.5.400

Abstract PDF

PURPOSE
The increased expression of cyclooxygenase (COX)-2 has been implicated in the development and progression of human cancer. This study investigated the COX-2 expression in colorectal cancer, and its relationships with tumor angiogenesis and the clinicopathological factors. MATERIALS AND METHODS: The expression of the COX-2 protein and microvessel density were evaluated, using immunohistochemical methods, in 21 normal colonic mucosa and 190 human colorectal carcinomas. Correlations between COX-2 expression and microvessel density, as well as various clinicopathological factors, were studied in colorectal carcinomas. RESULTS: The COX-2 protein expression in epithelial cells was increased in 169 of the 190 adenocarcinoma cases (88.9%), but in only 1 of the 21 (4.8%) normal mucosa cases. The COX-2 expression was significantly increased in the differentiated compared with the undifferentiated colorectal carcinomas (p<0.05), and significantly correlated with the depth of invasion and microvessel density (p<0.05). Rectal cancers had more COX-2 positive cases than the colon cancers (p<0.05). However, there were no significant differences in the tumor size and the presence of lymphatic or vascular invasion. CONCLUSION: The overexpression of cyclooxygenase-2 in colorectal carcinomas seems to play a role in the invasion and angiogenesis of the tumors, so may be a useful marker of the prognosis. The prominent expression was also demonstrated in differentiated colorectal cancers.

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Expression of Cyclooxygenase (COX)-2 as a Prognostic Factor in Nasopharyngeal Cancer
Kyubo Kim, Hong-Gyun Wu, Suk Won Park, Chong Jai Kim, Charn Il Park
Cancer Research and Treatment.2004; 36(3): 187. CrossRef

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19 Download
1 Crossref

Expression of Cyclooxygenase-2 in Human Breast Carcinoma: Relevance to Tumor Angiogenesis and Expression of Estrogen Receptor: Haeng Ji Kang, Gu Gong, Se Jin Jang, Pa Jong Jung, Chan Kum Park; Cancer Res Treat. 2001;33(4):286-295. Published online August 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.4.286

Abstract PDF

PURPOSE
This study investigates the COX-2 expression in human primary breast carcinomas and its relationship with both angiogenesis and the expression of estrogen receptor.
MATERIALS AND METHODS
COX-2 expression, angiogenesis, and estrogen receptor expression were examined by immunohistochemical methods in 167 human breast carcinomas by using monoclonal antibodies against COX-2, CD34, and estrogen receptor protein.
RESULTS
Although COX-2 was expressed in 77.8% of the breast carcinomas (130/167) regardless of histological types, it was not detected at all in benign epithelial cells. Interestingly, COX-2 expression was found to be significantly correlated with tumor angiogenesis (p=0.004), but not with estrogen receptor and other histopathologic parameters.
CONCLUSION
The results suggest that COX-2 expression occurs frequently in breast tissue during transformation of benign epithelial cells to malignant cells regardless of the estrogen receptor status. COX-2 expression may play a role in tumor angiogenesis that is responsible for tumor growth and metastasis.

Citations

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Hongryull Pyo, Yong Bae Kim, Nam Hoon Cho, Chang Ok Suh, Tchan Kyu Park, Yeon Sook Yun, Gwi Eon Kim
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Cancer Research and Treatment.2005; 37(2): 103. CrossRef
Clinical Value of Cyclooxygenase-2 Expression in Human Breast Carcinoma
Jin-Hee Ahn, Sung-Bae Kim, Sei-Hyun Ahn, Gyung-Yub Gong, Myung-Ju Ahn, Yoon-Koo Kang, Jung-Shin Lee, Woo Kun Kim
Cancer Research and Treatment.2004; 36(3): 192. CrossRef
Cyclooxygenase-2: A Potential Target in Human Cancer
Jong-Ho Won
Cancer Research and Treatment.2004; 36(3): 161. CrossRef
Expression of Cyclooxygenase (COX)-2 as a Prognostic Factor in Nasopharyngeal Cancer
Kyubo Kim, Hong-Gyun Wu, Suk Won Park, Chong Jai Kim, Charn Il Park
Cancer Research and Treatment.2004; 36(3): 187. CrossRef
Synchronous Coexpression of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in Carcinomas of the Uterine Cervix
Gwi Eon Kim, Yong Bae Kim, Nam Hoon Cho, Hyun-Cheol Chung, Hong Ryull Pyo, Jong Doo Lee, Tchan Kyu Park, Woong Sub Koom, Mison Chun, Chang Ok Suh
Clinical Cancer Research.2004; 10(4): 1366. CrossRef
Overexpression of cyclooxygenase‐2 is associated with a poor prognosis in patients with squamous cell carcinoma of the uterine cervix treated with radiation and concurrent chemotherapy
Yong Bae Kim, Gwi Eon Kim, Nam Hoon Cho, Hong Ryull Pyo, Su Jung Shim, Sei Kyung Chang, Hee Chul Park, Chang Ok Suh, Tchan Kyu Park, Byung Soo Kim
Cancer.2002; 95(3): 531. CrossRef

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