Annals of Coloproctology

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Efficacy of Immunohistochemical Staining in Differentiating a Squamous Cell Carcinoma in Poorly Differentiated Rectal Cancer: Two Case Reports: Sairafi Rami, Yoon Dae Han, Mi Jang, Min Soo Cho, Hyuk Hur, Byung Soh Min, Kang Young Lee, Nam Kyu Kim; Ann Coloproctol. 2016;32(4):150-155. Published online August 31, 2016; DOI: https://doi.org/10.3393/ac.2016.32.4.150

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A rectal carcinoma, including primary an adenosquamous and a squamous cell carcinoma (SCC), is a very rare disease, accounting for 0.025% to 0.20% of all large-bowel malignant tumors. Because SCCs have a higher mortality than adenosquamous carcinomas, determining whether the primary rectal cancer exhibits an adenomatous component or a squamous component is important. While differentiating between these 2 components, especially in poorly differentiated rectal cancer, is difficult, specific immunohistochemical stains enable accurate diagnoses. Here, we report the use of immunohistochemical stains to distinguish between the adenomatous and the squamous components in 2 patients with low rectal cancer, a 58-year-old man and a 73-year-old woman, who were initially diagnosed using the histopathologic results for a poorly differentiated carcinoma. These data suggest that using these immunohistochemical stains will help to accurately diagnose the type of rectal cancer, especially for poorly differentiated carcinomas, and will provide important information to determine the proper treatment for the patient.

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Cerebral metastasis from anal squamous cell carcinoma: A case report and literature review
Elena Popa, Vanesa Tomatis, Esther Quick, Paul Mitchell, Chrisovalantis Tsimiklis, Annika Mascarenhas
Oncology Letters.2025; 30(1): 1. CrossRef

Original Articles

Prognostic Significance of Tissue Leptin Expression in Colorectal Cancer Patients: Woon Kyung Jeong, Seong Kyu Baek, Mi Kyung Kim, Sun Young Kwon, Hye Soon Kim; Ann Coloproctol. 2015;31(6):222-227. Published online December 31, 2015; DOI: https://doi.org/10.3393/ac.2015.31.6.222

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Abstract PDF

Purpose

Leptin is encoded by the ob gene and is involved in the control of food intake and energy expenditure. Recent studies have implicated leptin expression to be an indicator of tumor features and prognosis. The purpose of this study was to investigate the association of tissue expression of leptin with the clinicopathological characteristics and clinical outcomes in colorectal cancer patients.

Methods

Patients who had undergone a curative surgical resection for a colorectal adenocarcinoma from 2000 to 2004 were included in the study. Immunohistochemical analyses of leptin expression were performed, and clinicopathological parameters were evaluated.

Results

Clinical data and tumor tissues of 146 patients were evaluated. The mean age was 68.6 ± 11.3 years, and 61.0% were men. Immunohistochemically, the rates of negative, weak, moderate, and strong leptin expression were 2.7% (4 of 146), 5.5% (8 of 146), 43.2% (63 of 146), and 48.6% (71 of 146), respectively. We compared the negative, weak, and moderate expression group (group A) with the strong expression group (group B). Leptin expression was inversely associated with nodal stage (P = 0.007) between the two groups. Leptin expression was not significantly associated with differentiation (P = 0.37), T stage (P = 0.16), and American Joint Committee on Cancer stage (P = 0.49), and no significant differences in the disease-free and the overall survivals (P = 0.78 and P = 0.61) were observed.

Conclusion

Results demonstrated an inverse association of nodal stage with high leptin expression. Higher leptin expression level might predict better oncologic outcome. However, further studies are warranted to identify the exact role of leptin expression in colorectal cancer.

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Leptin in colorectal cancer: literature review
Dhouha Bacha, Khouloud Ayed, Rahma Boughriba, Rym Akrout, Marwa Weslati, Asma Gati
Hormone Molecular Biology and Clinical Investigation.2025; 46(3): 103. CrossRef
CORRELATION OF LEPTIN AND ADIPONECTIN RECEPTOR EXPRESSION WITH CLINICOPATHOLOGICAL PARAMETERS IN COLORECTAL CARCINOMA - A CROSS-SECTIONAL PROSPECTIVE STUDY
Priyanka PARMESH, Udupi Shastri DINESH, Ajay S KHANDAGALE, Anil Bargale BAPU, Roshni SADASHIV, Pradnya REDDY
Arquivos de Gastroenterologia.2024;[Epub] CrossRef
The Effect of Serum Leptin Concentration and Leptin Receptor Expression on Colorectal Cancer
Sylwia Chludzińska-Kasperuk, Jolanta Lewko, Regina Sierżantowicz, Elżbieta Krajewska-Kułak, Joanna Reszeć-Giełażyn
International Journal of Environmental Research and Public Health.2023; 20(6): 4951. CrossRef
Decoding the role of leptin and adiponectin in obesity-related gastrointestinal cancer
Vanda Marques, Fabiola Arella, Marta B. Afonso, André A. Santos, Cecília M.P. Rodrigues
Clinical Science.2023; 137(15): 1095. CrossRef
Effects of conjugated linoleic acid supplementation on serum leptin levels, oxidative stress factors and tumor marker in rectal cancer patients undergoing preoperative chemoradiotherapy
Elnaz Faramarzi, Mohammad Mohammadzadeh, Sarvin Sanaie, Vibeke Andersen, Reza Mahdavi
Mediterranean Journal of Nutrition and Metabolism.2021; 14(3): 245. CrossRef
Leptin expression is substantially correlated with prognosis of urinary bladder carcinoma
Mohamad Nidal Khabaz, Imtiaz Ahmad Qureshi, Jaudah Ahmad Al-Maghrabi
Libyan Journal of Medicine.2021;[Epub] CrossRef
Leptin Overexpression as a Poor Prognostic Factor for Colorectal Cancer
Chunxiang Li, Jichuan Quan, Ran Wei, Zhixun Zhao, Xu Guan, Zheng Liu, Shuangmei Zou, Xishan Wang, Zheng Jiang, Jialiang Yang
BioMed Research International.2020;[Epub] CrossRef
Adipocytokines: Are they the Theory of Everything?
Pierre S. Maximus, Zeina Al Achkar, Pousette F. Hamid, Syeda S. Hasnain, Cesar A. Peralta
Cytokine.2020; 133: 155144. CrossRef
The prognostic and therapeutic role of hormones in colorectal cancer: a review
Stella Nikolaou, Shengyang Qiu, Francesca Fiorentino, Shahnawaz Rasheed, Paris Tekkis, Christos Kontovounisios
Molecular Biology Reports.2019; 46(1): 1477. CrossRef
Expression of leptin and leptin receptors in colorectal cancer—an immunohistochemical study
Saad M. Al-Shibli, Norra Harun, Abdelkader E. Ashour, Mohd Hanif B. Mohd Kasmuri, Shaikh Mizan
PeerJ.2019; 7: e7624. CrossRef
Expression of leptin in colorectal adenocarcinoma showed significant different survival patterns associated with tumor size, lymphovascular invasion, distant metastasis, local recurrence, and relapse of disease in the western province of Saudi Arabia
Jaudah Ahmed Al-Maghrabi, Imtiaz Ahmad Qureshi, Mohamad Nidal Khabaz
Medicine.2018; 97(34): e12052. CrossRef
Obesity-Related Colorectal Cancer: The Role of Leptin
Hyeong Rok Kim
Annals of Coloproctology.2015; 31(6): 209. CrossRef

Prognostic Implication of 15-Hydroxyprostaglandin Dehydrogenase Down-Regulation in Patients with Colorectal Cancer: Pil Sung Kang, Jin Ha Kim, Ok In Moon, Sung Chul Lim, Kyung Jong Kim; J Korean Soc Coloproctol. 2012;28(5):253-258. Published online October 31, 2012; DOI: https://doi.org/10.3393/jksc.2012.28.5.253

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Abstract PDF

Purpose

Prostaglandin (PG) E2 is known to be closely related to cancer progression and is inactivated by 15-hydroxyprostaglandin dehydrogenase (PGDH). 15-PGDH is shown to have tumor suppressor activity and to be down-regulated in various cancers, including colorectal cancer (CRC). Therefore, we evaluated the expression of 15-PGDH and its prognostic effect in patients with CRC.

Methods

15-PGDH expression was examined by using immunohistochemistry in 77 patients with CRC. Its prognostic significance was statistically evaluated.

Results

Negative 15-PGDH expression was noted in 55.8% of the 77 cases of CRC. 15-PGDH expression showed no correlation with any of the various clinicopathologic parameters. The status of lymph node metastasis, tumor-node-metastasis stages, and pre-operative carcinoembryonic antigen levels showed significant prognostic effect. However, univariate analysis revealed down-regulation of 15-PGDH not to be a predictor of poor survival. The 5-year overall survival rate was 71.7% in the group with positive expression of 15-PGDH and 67.1% in the group with negative expression of 15-PGDH, but this difference was not statistically significant (P = 0.751).

Conclusion

15-PGDH was down-regulated in 55.8% of the colorectal cancer patients. However, down-regulation of 15-PGDH showed no prognostic value in patients with CRC. Further larger scale or prospective studies are needed to clarify the prognostic effect of 15-PGDH down-regulation in patients with colorectal cancer.

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The tumor suppressor role and epigenetic regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in cancer and tumor microenvironment (TME)
SubbaRao V. Tulimilli, Medha Karnik, Anjali Devi S. Bettadapura, Olga A. Sukocheva, Edmund Tse, Gowthamarajan Kuppusamy, Suma M. Natraj, SubbaRao V. Madhunapantula
Pharmacology & Therapeutics.2025; 268: 108826. CrossRef
Molecular Targets in Precision Chemoprevention of Colorectal Cancer: An Update from Pre-Clinical to Clinical Trials
Nagendra S. Yarla, Venkateshwar Madka, Gopal Pathuri, Chinthalapally V. Rao
International Journal of Molecular Sciences.2020; 21(24): 9609. CrossRef

Matrix Metalloproteinase-2 and -7 Expression in Colorectal Cancer: Seong Woo Hong, Yun Kyung Kang, Byungmo Lee, Woo Yong Lee, Yeo Gu Jang, In Wook Paik, Hyucksang Lee; J Korean Soc Coloproctol. 2011;27(3):133-139. Published online June 30, 2011; DOI: https://doi.org/10.3393/jksc.2011.27.3.133

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Abstract PDF

Purpose

Matrix metalloproteinase-2 (MMP-2) and MMP-7 have been implicated in tumor growth and metastasis. This study aimed to investigate the expressions of MMP-2 and -7 in colorectal cancer and to evaluate their values as prognostic markers.

Methods

Immunohistochemical staining for MMP-2 and -7 was done in 144 resected colorectal cancer specimens. Clinicopathological data and survival results were compared with regard to the expression results.

Results

The expression rates of MMP-2 in tumor cells in the tumor center and the tumor border were 16.7% and 38.9%, respectively. That of MMP-2 in stromal cells was 27.8%. MMP-7 immunoreactivities of tumor cells in the tumor center and the tumor border were 6.9% and 23.6%. The expressions of MMP-2 and MMP-7 were correlated. MMP-2 expression in stromal cells was more increased in the distal part of the colorectum: 8.8% in right colon cancer, 29.5% in left colon cancer and 36.4% in rectal cancer. MMP-2 expression of tumor cells in the tumor border was correlated with T-stage. MMP-7 expression of tumor cells in the tumor border was increased in case of infiltrative cancer compared with fungating tumor. The expression patterns of MMP-2 and -7 were not correlated with other clinicopathological factors, including tumor markers, node metastasis, distant metastasis, lymphatic invasion, tumor differentiation, and recurrence. No significant associations between the overall and disease-free survival rates and the MMP-2 and -7 expression patterns were noted.

Conclusion

The high expression rates of MMP-2 and -7 in tumor borders suggest that MMP-2 and -7 have some role in tumor invasion, but in this study, MMP-2 and -7 did not appear to be significant predictors of prognosis in colorectal cancer.

Citations

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A review of matrix metalloproteinase-2-sensitive nanoparticles as a novel drug delivery for tumor therapy
Lanlan Zong, Hongliang Xu, Huiqi Zhang, Ziwei Tu, Xiao Zhang, Shumin Wang, Meigui Li, Yu Feng, Binke Wang, Luhui Li, Xinmei Xie, Zhonggui He, Xiaohui Pu
International Journal of Biological Macromolecules.2024; 262: 130043. CrossRef
Prognostic value of integrin αV expression and localization pattern in invasive breast carcinomas
Otto Luiz Dutra Cerqueira, Mayara Carolline Silva Botelho, Ana Paula Zen Petisco Fiore, Cynthia Aparecida Bueno de Toledo Osório, Rebeka Tomasin, Mauro César Cafundó Morais, Rossana Verónica Mendoza López, Elaine Cristina Cardoso, Santiago Andres Vilella-
Neoplasia.2022; 30: 100803. CrossRef
Effect of ginger extracts on colorectal cancer HCT-116 cell line in the expression of MMP-2 and KRAS
Shiva Malmir, Asa Ebrahimi, Frouzandeh Mahjoubi
Gene Reports.2020; 21: 100824. CrossRef
Proteome Heterogeneity in Colorectal Cancer
Lay Cheng Lim, Yang Mooi Lim
PROTEOMICS.2018;[Epub] CrossRef
Implications of Isoprostanes and Matrix Metalloproteinase-7 Having Potential Role in the Development of Colorectal Cancer in Males
Mahmood Rasool, Arif Malik, Ahmad Ashar Ghuman, Muhammad Abdul Basit Ashraf, Mahwish Arooj, Sulayman Waquar, Sara Zahid, Sumera Shaheen, Aamer Qazi, Muhammad Imran Naseer, Mazin A. Zamzami, Ayat Al-Ghafari, Othman A. Baothman, Mustafa Zeyadi, Nawal Helmi,
Frontiers in Oncology.2018;[Epub] CrossRef
Circulating gelatinases are not prognostic of treatment response and survival in locally advanced rectal cancer patients undergoing preoperative chemoradiotherapy
Sukran Ulger, Diclehan Kilic, Fatih Demircioglu, Canan Y Demirtas, Ozge T. Pasaoglu
Journal of Cancer Research and Therapeutics.2018; 14(Suppl 1): S90. CrossRef
Profile of Expression of Genes Encoding Matrix Metallopeptidase 9 (MMP9), Matrix Metallopeptidase 28 (MMP28) and TIMP Metallopeptidase Inhibitor 1 (TIMP1) in Colorectal Cancer: Assessment of the Role in Diagnosis and Prognostication
Zbigniew Lorenc, Dariusz Waniczek, Katarzyna Lorenc-Podgórska, Wiktor Krawczyk, Maciej Domagała, Mateusz Majewski, Urszula Mazurek
Medical Science Monitor.2017; 23: 1305. CrossRef
Matrix Metalloproteinase-2 and -9, Lactate, and Malate Dehydrogenase and Lipid Peroxides in Sera of Patients with Colorectal Carcinoma
Kristina Gopcevic, B. Rovcanin, D. Kekic, Z. Krivokapic, V. Dragutinovic
Folia Biologica.2017; 63(5-6): 190. CrossRef
Prognostic significance of plasma matrix metalloprotease-2 in pancreatic cancer patients
Nidhi Singh, Surabhi Gupta, Ravindra M. Pandey, Peush Sahni, Shyam S. Chauhan, Anoop Saraya
Indian Journal of Medical Research.2017; 146(3): 334. CrossRef
CD147 and matrix-metalloproteinase-2 expression in metastatic and non-metastatic uveal melanomas
Julia Lüke, Vlatka Vukoja, Tim Brandenbusch, Khaled Nassar, Jens Martin Rohrbach, Salvatore Grisanti, Matthias Lüke, Aysegül Tura
BMC Ophthalmology.2016;[Epub] CrossRef
High Expression of Matrix Metalloproteinases: MMP-2 and MMP-9 Predicts Poor Survival Outcome in Colorectal Carcinoma
Nada Salem, Ibrahim Kamal, Jaudah Al-Maghrabi, Adel Abuzenadah, Abdul Ali Peer-Zada, Yousif Qari, Mahmoud Al-Ahwal, Mohammed Al-Qahtani, Abdelbaset Buhmeida
Future Oncology.2016; 12(3): 323. CrossRef
Rab11-FIP2 promotes colorectal cancer migration and invasion by regulating PI3K/AKT/MMP7 signaling pathway
Chang-long Xu, Jian-zhang Wang, Xuan-ping Xia, Chen-wei Pan, Xiao-xiao Shao, Sheng-long Xia, Shou-xing Yang, Bo Zheng
Biochemical and Biophysical Research Communications.2016; 470(2): 397. CrossRef
Shikonin inhibits the cell viability, adhesion, invasion and migration of the human gastric cancer cell line MGC-803 via the Toll-like receptor 2/nuclear factor-kappa B pathway
Ji Ping Liu, Dan Liu, Jun Fei Gu, Mao Mao Zhu, Li Cui
Journal of Pharmacy and Pharmacology.2015; 67(8): 1143. CrossRef
Prognostic significance of MMP-7 expression in colorectal cancer: A meta-analysis
Da-wei Sun, Ying-yi Zhang, Yue Qi, Xing-tong Zhou, Guo-yue Lv
Cancer Epidemiology.2015; 39(2): 135. CrossRef
Immunoexpression of metalloproteinase 14 and tissue inhibitor of metalloproteinase 2 in colorectal carcinomas and lymph node metastases
Francisco Nélson Nóbrega Furtado, João Paulo Aguiar Sampaio, João Tarcisio Alves Maia-Filho, Renato Braga Vieira, Roberto César Pereira Lima-Júnior, Ronaldo Albuquerque Ribeiro, Paulo Roberto Carvalho Almeida
Comparative Clinical Pathology.2015; 24(6): 1367. CrossRef
MMP-2/9-oriented combinations enhance antitumor efficacy of EGFR/HER2-targeting fusion proteins and gemcitabine
YE QIN, XIU-JUN LIU, LIANG LI, XU-JIE LIU, YI LI, RUI-JUAN GAO, RONG-GUANG SHAO, YONG-SU ZHEN
Oncology Reports.2014; 32(1): 121. CrossRef
Prognostic Role of Tumor-Associated Proteases in Colorectal Cancer
N. E. Kushlinskii, E. S. Gershtein, E. A. Korotkova, V. V. Prorokov
Bulletin of Experimental Biology and Medicine.2013; 154(3): 365. CrossRef
Novel roles of liver sinusoidal endothelial cell lectin in colon carcinoma cell adhesion, migration and in-vivo metastasis to the liver
Yunfei Zuo, Shuangyi Ren, Min Wang, Biao Liu, Juntao Yang, Xuezhang Kuai, Changwei Lin, Dianyuan Zhao, Li Tang, Fuchu He
Gut.2013; 62(8): 1169. CrossRef
Patterns of FOXE1 Expression in Papillary Thyroid Carcinoma by Immunohistochemistry
Andrey Bychkov, Vladimir Saenko, Masahiro Nakashima, Norisato Mitsutake, Tatiana Rogounovitch, Alyaksandr Nikitski, Florence Orim, Shunichi Yamashita
Thyroid.2013; 23(7): 817. CrossRef
Matrix metalloproteinase 2 overexpression and prognosis in colorectal cancer: a meta-analysis
Mumu Shi, Bo Yu, Hongguo Gao, Jingwen Mu, Changwei Ji
Molecular Biology Reports.2013; 40(1): 617. CrossRef

Clinicopathologic Features of Sporadic Colorectal Cancer with MLH1/MSH2 Loss of Expression - Reduced Likelihood of Metastases.: Park, Ji Won , Chang, Hee Jin , Jung, Kyung Hae , Kim, Dae Yong , Sohn, Dae Kyung , Han, Kyung Soo , Hong, Chang Won , Lim, Seok Byung , Choi, Hyo Seong , Jeong, Seung Yong , Lee, Sang Jeon; J Korean Soc Coloproctol. 2008;24(3):175-183.; DOI: https://doi.org/10.3393/jksc.2008.24.3.175

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Abstract PDF

PURPOSE
This study was designed to determine the frequency of MMR defective sporadic colorectal cancer (CRC) by using immunohistochemistry and to investigate the correlation between the MMR status and the metastatic potential.
METHODS
The study included 249 patients with sporadic colorectal cancer who underwent surgical resection. The MMR status was determined by using an immunohistochemical analysis of MLH1 and MSH2 expression. RESULTS: Twenty seven (10.8%) carcinomas showed abnormal MMR protein expression (18 MLH1 negative and 9 MSH2 negative) and were classified as MMR defective tumors whereas 222 tumors demonstrated normal MLH1/MSH2 immunoreactivity (MMR intact tumor). MMR defective tumors developed at significantly higher frequencies in a proximal site (59.3% vs. 27.5%, P=0.001) and tended to be larger in size (6.3+/-2.4 cm vs. 5.1+/-2.1 cm, P=0.026). They showed significantly lower overall stage, N stage, and M stage at the time of diagnosis (P=0.002, P=0.014, P=0.010, respectively). In patients who had MMR defective tumors, lymphocytic infiltration (40.7% vs. 8.7%, P<0.001) and poor differentiation (22.2% vs. 11.7%, P=0.012) were more frequently observed. Less frequently MMR defective tumors displayed lymphatic invasion (40.7% vs. 67.1%, P=0.007) and infiltrative borders (22.2% vs. 51.8%, P=0.004). The MMR defect was strongly associated with a decreased likelihood of lymph node (odds ratio: 0.34, 95% CI: 0.13~0.95) and distant organ metastases at diagnosis (odds ratio: 0.09, 95% CI: 0.01~0.94), independent of the clinicopathologic features. CONCLUSIONS: mmunohistochemical analysis revealed that 10.8% of sporadic CRC cases showed no staining for MLH1 or MSH2. Lymphatic invasion and distant metastases were found at lower rates in these MMR defective tumors.

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Characterization of RNA editome in primary and metastatic lung adenocarcinomas
Lihua Peng, Leo J Lee, Heng Xiong, Hong Su, Junhua Rao, Dakai Xiao, Jianxing He, Kui Wu, Dongbing Liu
Oncotarget.2017; 8(7): 11517. CrossRef
Prognostic Impact of Microsatellite Instability in Colorectal Cancer Presenting With Mucinous, Signet-Ring, and Poorly Differentiated Cells
Sang Hun Jung, So Hyun Kim, Jae Hwang Kim
Annals of Coloproctology.2016; 32(2): 58. CrossRef
Microsatellite instability testing in Korean patients with colorectal cancer
Jung Ryul Oh, Duck-Woo Kim, Hye Seung Lee, Hee Eun Lee, Sung Min Lee, Je-Ho Jang, Sung-Bum Kang, Ja-Lok Ku, Seung-Yong Jeong, Jae-Gahb Park
Familial Cancer.2012; 11(3): 459. CrossRef

Pathological Analysis of Tumor Response after Preoperative Chemoradiation Therapy for Advanced Rectal Cancer.: Lee, Seok Young , Choi, Yoon Jung , Kang, Jung Gu , Chung, Eun Ji , Kim, Yong Tai; J Korean Soc Coloproctol. 2007;23(6):511-517.; DOI: https://doi.org/10.3393/jksc.2007.23.6.511

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Abstract PDF

PURPOSE
We investigated the association of survivin expression with the prognosis in advanced rectal cancer with preoperative chemoradiotherapy for pathological analysis.
METHODS
We examined 16 patients with rectal cancer who were preoperatively staged as T3 or T4. The enrolled patients were given 5-FU, 425 mg/m2/day, and leucovorin, 20 mg/m2/day, intravenously for 3 days during weeks 1 and 5 of pelvic radiotherapy. Surgical resection was performed 4~6 weeks after completion of the schedule. Tumor response was divided into CR (complete remission), PR (partial remission), and NR (non remission). Immunohistochemical staining of paraffin sections using monoclonal antibodies for survivin, bcl-2, and p53 was performed on pretreatment biopsy and surgically resected tissue by using the standard avidin-biotin-peroxidase technique.
RESULTS
No CR was achieved. PR was achieved in 10 patients (62.5%), and NR in 6 patients (37.5%). After preoperative treatment, survivin expression tended to be decreased in tumor cells (62.5% to 31.3%) and slightly increased in adjacent normal mucosa a (12.5% to 25%). After preoperative treatment, survivin expression was correlated with lymph-node metastasis in the statistical analysis. We failed to find any other significant relationship between survivin expression and any parameters, except lymph node metastasis and apoptotic index.
CONCLUSIONS
Survivin expression before preoperative treatment was not related to the prognosis in rectal cancer patients, but survivin expression after preoperative treatment was related to lymph node metastasis of advanced rectal cancer. Further studies, including large numbers of rectal cancer cases with a sufficient follow-up period, are needed in order to establish survivin as a prognostic target in rectal cancer.

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Clinicopathologic significance of survivin expression in colorectal adenocarcinoma
Woong Na, Se Min Jang, Young Jin Jun, Young Soo Song, Ki‐Seok Jang, Kang Hong Lee, Kyeong Geun Lee, Hong Xiu Han, Seung Sam Paik
Basic and Applied Pathology.2009; 2(3): 94. CrossRef

Methodologic Evaluation of EGFR Expression in Colorectal Cancer.: Oh, Soo Youn , Yoon, Se Jin , Cheon, Seung Hui , Lee, Ryung Ah , Kang, Bo Young , Lee, Shi Nae , Chung, Soon Sup , Kim, Kwang Ho; J Korean Soc Coloproctol. 2006;22(2):75-80.

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Abstract PDF: PURPOSE
The epidermal growth factor receptor (EGFR) is a one of the transmembrane receptor proteins that play an important role in initiating tumor cell signaling and growth and is regarded as a promising target for cancer therapy. The EGFR expression rate has been reported to vary according to the detection method. The aims of this study were to evaluate the EGFR expression rate of a colorectal carcinoma by using immunohistochemical staining (IHC) and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and to analyze the correlation between these methods.
METHODS
EGFR expression was investigated in tissue sections from 33 patients with a colorectal adenocarcinoma by using IHC and semiquantitative RT-PCR. IHC was performed with antibodies in a 1:40 dilution and a 1:80 dilution. The results of the three detection methods were compared with one another.
RESULTS
The mean age of the patients was 61.9+/-12.2 years, and the male-to-female ratio was 1.2:1. The EGFR expression rates were 93.9% (31/33) in IHC with a 1:40 dilution, 87.9% (29/33) in IHC with a 1:80 dilution, and 66.7% (22/33) in RT-PCR. The result of IHC with a 1:40 dilution significantly correlated with the result of IHC with a 1:80 dilution (Pearson correlation 0.684, P<0.01). There was no correlation between semiquantitative RT-PCR and IHC (1:40 dilution, 1:80 dilution).
CONCLUSIONS
The EGFR expression obtained by using IHC was consistent with different antibody dilutions. The expression rate obtained by using RT-PCR was significantly lower than that obtained by using IHC, and there was no statistical correlation between the expressions of EGFR obtained by using RT-PCR and IHC. A standardization for EGFR detection methods is needed to draw any conclusion concerning their activity in colorectal cancer.

COX-2 and iNOS Expression and Microvessel Density by Microsatellite Instability in Colorectal Cancer.: Jin, So Young , Kim, Jin Won , Jang, Yong Seog , Kim, Jae Joon , Hong, Sung Ho , Cho, Choo Yon; J Korean Soc Coloproctol. 2005;21(1):27-35.

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Abstract PDF: PURPOSE
We tried to identify the overall incidence of microsatellite instability (MSI) and the utility of mismatch repair (MMR) protein expression in sporadic colorectal cancers in Korean. We also investigate the role of angiogenesis in colorectal cancers by MSI status.
METHODS
A total 85 resected colorectal cancers were submitted for MSI study using PCR methods with 5 markers and immunohistochemistry (IHS) for hMLH1 and hMSH2. Expression of COX-2 and iNOS and microvessel density by IHS were correlated with various clinicopathologic prognostic factors.
RESULTS
Among 85 cases of sporadic colorectal cancers, MSI was observed in 11 cases (12.9%) including 10 MSI-H and 1 MSI-L cases. Patients with MSI (+) showed female prevalence (1.75 : 1), low Dukes stage, mucinous histologic type, and Crohn-like lymphoid reaction than those with MSS. Overall sensitivity of hMLH1 and/or hMSH2 expression was 98.6% and specificity was 72.7%. iNOS expression was significantly correlated with COX-2 expression in tumor cells (P=0.006), however, they were not correlated with MSI status. High microvessel density was correlated with hMLH1 expression (P=0.025), COX-2 expression (P= 0.05), and Crohn-like lymphoid reaction (P=0.041).
CONCLUSIONS
IHS for MMR proteins is a valuable substitute of MSI status and COX-2 related neoangiogenesis is thought to be related to inhibition of microsatellite unstable colorectal cancer progression via decreased microvessel density.

Expression of beta-catenin in Colorectal Cancer with Liver Metastasis.: Han, Sang Ah , Park, Chi Min , Kang, Sin Jae , Song, Sang Yong , Kim, Sang Hee , Son, Dae Soon , Yun, Seong Hyeon , Lee, Woo Yong , Chun, HoKyung; J Korean Soc Coloproctol. 2004;20(6):391-398.

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Abstract PDF: PURPOSE
Decreased expression of beta-catenin has been known to be associated with tumor metastasis. However, the clinical relationship between the degree of expression and the prognosis in colorectal cancer (CRC) remains unclear. In this study, we evaluated the prognostic value of beta-catenin expression in CRC patients with liver metastasis.
METHODS
Paraffin embedded blocks were obtained from 70 patients who underwent potentially curative resection for CRC with liver metastasis. Samples from normal colon mucosa, primary CRC and metastatic liver lesion were prepared in tissue microarrays and were stained by immunohistochemistry with monoclonal antibody against beta- catenin. The membranous beta-catenin expression was assessed and the beta-catenin expression difference between primary CRC and metastatic liver lesion was analysed in relation to overall survival as well as disease free survival rates.
RESULTS
In beta-catenin expression, preserved expression (score >6) was observed in 42.0%, and 21.9% of primary CRC tumor samples and tumor samples from metastatic liver lesion respectively. The degree of beta-catenin expression in metastatic liver lesion was significantly lower than that in primary CRC (P=0.022). According to the difference of beta-catenin expression score between primary CRC and liver metastasis, patients were classified as group 'A' and 'B'. Group 'A' was defined as patients showing remarkably decreased expression of beta-catenin in metastatic liver lesion in that the difference of the score was three or more. Group 'B' was defined as patients showing maintained or increased beta-catenin expression in metastatic liver lesion in comparison to primary CRC, in that the difference of beta-catenin expression score was less than three. Overall survival rate and disease free survival rate were significantly better in group 'B' than group 'A' (P=0.02, P=0.002).
CONCLUSIONS
Decreased expression of beta-catenin in metastatic liver lesion may be a poor prognostic marker in colorectal cancers with liver metastasis. A further large-scaled investigation is necessary to define the role of beta-catenin in CRC.

Clinicopathologic and Immunohistochemical Features of Gastrointestinal Stromal Tumors (GISTs) in the Colon & Rectum.: Park, Kil Chun , Kim, Hee Cheol , Park, In Ja , Yu, Chang Sik , Kim, Jung Sun , Kim, Jin Cheon; J Korean Soc Coloproctol. 2004;20(6):371-377.

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Abstract PDF: PURPOSE
A gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. There are only few reports in the literature describing colorectal GISTs. The aim of this study was to evaluate the clinicopathologic features of colorectal GISTs and to verify prognostic factors.
METHODS
We reviewed 14 patients diagnosed as having primary colorectal GISTs between 1992 and 2003. Clinicopathologic variables and immunohistochemical expressions were analyzed. The diagnostic criteria and grading system for the GISTs were based on the proposal by the National Institutes of Health in April 2001. The median follow-up period was 27 (1~137) months.
RESULTS
The male-to-female ratio was 9 : 5, and the mean age was 61 (37~76) years. The primary location was the rectum (11 cases, 78.6%). The mean tumor size was 7.7 (1.5~17) cm, and the mean number of mitoses was 33.4 (1~150) per 50 HPF. Of the 14 patients, 10 patients (71.4%) were regarded as a high-risk group and four patients as an intermediate-risk group. KIT protein and CD34 were expressed in 92.9% and 78.6% of the cases, respectively. The patients were subclassified based on immunohistochemical expressions as an uncommitted type in 11 cases (78.6%), a combined type in 2 cases (14.3%), and a myoid type in 1 (7.1%) case. Recurrence occured in three patients (21.4%) who were in the high-risk group.
CONCLUSIONS
Colorectal GISTs occurred predominantly in the rectum and tended to be classified as high risk, which was the most important risk factor for recurrence. Accurate diagnosis and grading are important for adequate treatment and accurate prognosis.

Clinical Significance of Lymph Node Micrometastasis in Patients with Dukes' B Colorectal Cancer.: Lee, Hyo Won , Jang, Yong Seog; J Korean Soc Coloproctol. 2004;20(1):57-63.

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Abstract PDF: PURPOSE
This study aimed to provide immunohistochemical evidence of micrometastasis in patients with node-negative Dukes' B colorectal cancer and to evaluate the clinical implications, including prognostic significance, of lymphatic metastasis.
METHODS
A retrospective study of 90 patients who underwent a curative operation due to colorectal neoplasms from 1996 to 2001 was performed. Two consecutive sections of lymph nodes were prepared: one for ordinary hematoxylin-eosin staining, and the other for immunohistochemistry with pancytokeratine antibody. All clinical factors, including survival rate, were compared between patients with and without lymph-node metastasis. The mean follow- up period was 36.1 months.
RESULTS
Micrometastasis was confirmed in 115 nodes (7.9%) from 32 patients (35.6%). No correlations were observed between micrometastases and prognostic factors, including survival rate, except for lymphatic invasion and postoperative TNM staging. Twenty-six of the 32 (81.3%) patients with micrometastases belonged to stage T3N0M0 (P<0.003).
CONCLUSIONS
The immunohistochemical assay may be a useful way to identify micrometastasis in patients with Dukes' B colorectal neoplasms, but we were not able to demonstrate the prognostic significance of micrometastasis.

hMLH1/hMSH2 Protein Expression in Sporadic Colorectal Carcinoma and Its Clinicopathological Significance.: Kang, Jae Hee , Lee, Kil Yeon , Lee, Kee Hyung , Yoon, Choong , Oh, Soo Myung , Lee, Joo Hee; J Korean Soc Coloproctol. 2001;17(1):38-46.

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Abstract PDF: PURPOSE
DNA replication errors (RERs) in repeated nucleotide sequences (microsatellite instability) is caused by defective mismatch repair (MMR) genes. Ninety percent of colorectal carcinomas in hereditary nonpolyposis colorectal cancer (HNPCC) patients and 10-15% of sporadic colorectal cancers show microsatellite instability. In the majority of colorectal cancers with microsatellite instability, the defective MMR gene is hMLH1 or hMSH2. The author examined immunohistochemical expression of hMLH1 and hMSH2 in 75 cases of colorectal carcinomas excluding HNPCC, based on Amsterdam criteria for investigating clinicopathological characteristics and prognosis in hMLH1/hMSH2 negative cases.
METHODS
Formalin fixed, paraffin blocks obtained from tumors of 75 cases of colorectal cancers were stained with two monoclonal antibodies (hMLH1 and hMSH2). The correlation between hMLH1/hMSH2 negativity, and clinicopathological feature and prognosis were statistically analysed.
RESULTS
Twelve cases (16.0%) showed hMLH1/hMSH2 negativity. Negative expression of hMLH1/hMSH2 was associated with early onset (under age 50), proximal location, multiplicity, mucinous histologic type and poor differentiation. There was a significant survival advantage in patients with hMLH1/hMSH2 negative colorectal carcinoma.
CONCLUSIONS
This study shows that hMLH1/hMSH2 negative colorectal carcinomas have the same clinicopathological characteristics of colorectal carcinomas with microsatellite instability. The immunohistochemical test for hMLH1/hMSH2 protein can be a simple screening method routinely applicable. The result of this test is available for establishing guidelines for management, and an independent prognostic factor for sporadic colorectal cancers.

Clinical Significance of Lymph Node Micrometastasis in Dukes' Stage A&B Colorectal Cancer: An Immunohistochemical Study.: Kim, Tae Soo , Hwang, Jae Kwan , Bae, Sun Young , Kim, Yang Hee , Hong, Kee Chun , Ahn, Seung Ik , Hur, Yoon Seok , Han, Hye Seung , Woo, Ze hong; J Korean Soc Coloproctol. 1999;15(4):253-261.

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Abstract PDF: PURPOSE
Lymph node metastasis is the most important prognostic factor in colorectal cancer. However, 20~30% of patients with lymph node negative colorectal cancer die of recurrent disease. We investigated whether the detection of micrometastasis is of any clinical significance in Dukes' stage A & B colorectal cancer.
METHODS
Ninety patients who underwent curative resection of colorectal cancer from Aug. of 1996 to Jan. of 1999 were entered the study. For examination, we used paraffin blocks of lymph nodes which were metastasis-free by conventional histopathology. After preparation of tissue blocks using the serial sectioning technique, the specimens were stained with immunohistochemical method using anticytokeratin antibody. And the hematoxylin-eosin staining was repeated.
RESULTS
We disclosed micrometastases in 15 of 90 cases, mostly located in subcapsular sinuses. And in 8 of 15 cases, we also found metastases in repeated H&E staining. There were no significant relationship between the detection of micrometastases and the depth of wall invasion, the histological grade and the status of lymphovascular invasion. With median follow-up of 15 months, we found no significant difference in recurrence between the micrometasis positive and negative groups.
CONCLUSIONS
The result showed that the micrometastasis of lymph node in colorectal caner might increase the risk for development of tumor recurrence. But because of small numbers of recurrent cases and relatively short follow-up period, there was no statistically significant relationship between micrometastasis negative and positive groups.

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