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Breast cancer
Changes in Invasive Breast Carcinomas after Neoadjuvant Chemotherapy Can Influence Adjuvant Therapeutic Decisions
Bárbara Jaime dos Santos, Débora Balabram, Virginia Mara Reis Gomes, Carolina Costa Café de Castro, Paulo Henrique Costa Diniz, Marcelo Araújo Buzelin, Cristiana Buzelin Nunes
Cancer Res Treat. 2024;56(1):178-190.   Published online August 1, 2023
DOI: https://doi.org/10.4143/crt.2023.386
AbstractAbstract PDFPubReaderePub
Purpose
Neoadjuvant chemotherapy (NACT) can change invasive breast carcinomas (IBC) and influence the patients’ overall survival time (OS). We aimed to identify IBC changes after NACT and their association with OS.
Materials and Methods
IBC data in pre- and post-NACT samples of 86 patients were evaluated and associated with OS.
Results
Post-NACT tumors changed nuclear pleomorphism score (p=0.025); mitotic count (p=0.002); % of tumor-infiltrating inflammatory cells (p=0.016); presence of in situ carcinoma (p=0.001) and lymphovascular invasion (LVI; p=0.002); expression of estrogen (p=0.003), progesterone receptors (PR; p=0.019), and Ki67 (p=0.003). Immunohistochemical (IHC) profile changed in 26 tumors (30.2%, p=0.050). Higher risk of death was significatively associated with initial tumor histological grade III (hazard ratio [HR], 2.94), high nuclear pleomorphism (HR, 2.53), high Ki67 index (HR, 2.47), post-NACT presence of LVI (HR, 1.90), luminal B–like profile (HR, 2.58), pre- (HR, 2.26) and post-NACT intermediate mitotic count (HR, 2.12), pre- (HR, 4.45) and post-NACT triple-negative IHC profile (HR, 4.52). On the other hand, lower risk of death was significative associated with pre- (HR, 0.35) and post-NACT (HR, 0.39) estrogen receptor–positive, and pre- (HR, 0.37) and post-NACT (HR, 0.57) PR-positive. Changes in IHC profile were associated with longer OS (p=0.050). In multivariate analysis, pre-NACT grade III tumors and pre-NACT and post-NACT triple negative IHC profile proved to be independent factors for shorter OS.
Conclusion
NACT can change tumor characteristics and biomarkers and impact on OS; therefore, they should be reassessed on residual samples to improve therapeutic decisions.
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The Use of CD44 Variant 9 and Ki-67 Combination Can Predicts Prognosis Better Than Their Single Use in Early Gastric Cancer
Se-Il Go, Gyung Hyuck Ko, Won Sup Lee, Jeong-Hee Lee, Sang-Ho Jeong, Young-Joon Lee, Soon Chan Hong, Woo Song Ha
Cancer Res Treat. 2019;51(4):1411-1419.   Published online February 25, 2019
DOI: https://doi.org/10.4143/crt.2018.663
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We previously demonstrated that CD44v9 and Ki-67 played an important role in predicting poor prognosis of early gastric cancer (EGC). However, little is known about combined use of both biomarkers as prognostic biomarker. The present study was performed to investigate the significance of CD44v9 and Ki-67 expression as a combination biomarker for EGC.
Materials and Methods
With tissue microarray for 158 EGC tissues, we performed immunohistochemical staining for CD44v9 and Ki-67. The whole patients were divided into three groups (group A, CD44v9- negative/Ki-67–low; group B, neither group A or C; and group C, CD44v9-positive/Ki-67– high). Its clinical significance was re-analyzed with adjustment via propensity score matching (PSM). For validation, we performed bootstrap resampling.
Results
The median follow-up duration was 90.4 months (range, 3.7 to 120.4 months). In the comparison according to CD44v9/Ki-67 expression, the combined use of the two biomarker clearly separated the three groups by 5-year survival rates (5-YSR, 96.3%, 89.8%, and 76.8% in group A, B, and C, respectively; p=0.009). After PSM, 5-YSR were 97.7% and 76.8% in group A+B and group C, respectively (p=0.002). Multivariable analysis demonstrated that group C had independently poor prognosis (hazard ratio, 9.137; 95% confidence interval, 1.187 to 70.366; p=0.034) compared with group A. Bootstrap resampling internally validated this result (p=0.016).
Conclusion
This study suggests that both positive CD44v9 and high Ki-67 expression are associated with poor prognosis in EGC, and the combined use of these markers provides better prognostic stratification than the single use of them.

Citations

Citations to this article as recorded by  
  • The Prognostic Importance of Ki-67 in Gastrointestinal Carcinomas: A Meta-analysis and Multi-omics Approach
    Mahdieh Razmi, Fatemeh Tajik, Farideh Hashemi, Ayna Yazdanpanah, Fatemeh Hashemi-Niasari, Adeleh Divsalar
    Journal of Gastrointestinal Cancer.2024; 55(2): 599.     CrossRef
  • Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma
    Juan Lin, Zhu-Feng Chen, Guo-Dong Guo, Xin Chen
    World Journal of Gastrointestinal Oncology.2024; 16(3): 687.     CrossRef
  • Significance of concurrent evaluation of HER2 gene amplification and p53 and Ki67 expression in gastric cancer tissues
    Su-nan Wang, Yang-kun Wang, Chao-ya Zhu, Bo Jiang, Dong-feng Ge, Ying-ying Li
    Clinical and Translational Oncology.2024;[Epub]     CrossRef
  • Analysis of risk factors for lymph node metastasis and prognosis study in patients with early gastric cancer: A SEER data-based study
    Jinzhou Li, Ting Cui, Zeping Huang, Yanxi Mu, Yalong Yao, Wei Xu, Kang Chen, Haipeng Liu, Wenjie Wang, Xiao Chen
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Revisiting therapeutic strategies for ovarian cancer by focusing on redox homeostasis (Review)
    Hiroshi Kobayashi, Shogo Imanaka, Hiroshi Shigetomi
    Oncology Letters.2022;[Epub]     CrossRef
  • Cyclin D1 Serves as a Poor Prognostic Biomarker in Stage I Gastric Cancer
    Se-Il Go, Gyung Hyuck Ko, Won Sup Lee, Jeong-Hee Lee, Sang-Ho Jeong, Young-Joon Lee, Soon Chan Hong, Woo Song Ha
    Current Issues in Molecular Biology.2022; 44(3): 1395.     CrossRef
  • Analysis of Endoscopy Findings to Identify Early Gastric Cancers with Tumor Budding: A Retrospective Study
    Lanqing Cao, Zhaoyong Wang, Liwei Duan, Lijuan Wei
    Journal of Gastrointestinal Surgery.2021; 25(7): 1706.     CrossRef
  • Clinical significance of circulating tumour cells and Ki-67 in renal cell carcinoma
    Jinbo Song, Zhe Yu, Bingqi Dong, Mingkai Zhu, Xiaofeng Guo, Yongkang Ma, Shiming Zhao, Tiejun Yang
    World Journal of Surgical Oncology.2021;[Epub]     CrossRef
  • Fascin‑1 is associated with recurrence in solitary fibrous tumor/hemangiopericytoma
    Yumiko Yamamoto, Yoshihiro Hayashi, Hideyuki Sakaki, Ichiro Murakami
    Molecular and Clinical Oncology.2021;[Epub]     CrossRef
  • Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer
    Jie Yang
    Medical Oncology.2020;[Epub]     CrossRef
  • Roles of Proteoglycans and Glycosaminoglycans in Cancer Development and Progression
    Jinfen Wei, Meiling Hu, Kaitang Huang, Shudai Lin, Hongli Du
    International Journal of Molecular Sciences.2020; 21(17): 5983.     CrossRef
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Reduced Expression of E-cadherin in Human Non-small Cell Lung Carcinoma
Na-Hye Myong
Cancer Res Treat. 2004;36(1):56-61.   Published online February 29, 2004
DOI: https://doi.org/10.4143/crt.2004.36.1.56
AbstractAbstract PDFPubReaderePub
Purpose

E-cadherin, a calcium-dependent cell to cell adhesion molecule, plays a key role in the maintenance of tissue integrity. Reduction or loss of E-cadherin has been reported to have a role in the development of human malignancies. The expression of E-cadherin was analyzed in human non-small cell lung carcinoma (NSCLC) to elucidate the role in pulmonary carcinogenesis and determine the relationship with several clinicopathological factors and the prognosis.

Materials and Methods

Sixty five human cases of NSCLC were evaluated by immunohistochemical analysis for the expression of E-cadherin. The immunostaining results for E-cadherin were semiquantitatively interpreted, as preserved and reduced, in the tumor tissues. The E-cadherin expression was analyzed in relation to several clinicopathological data and the survival. The cell proliferation index of the tumors was evaluated by immunostaining with the Ki-67 antigen.

Results

Reduced E-cadherin expression was found in 51 cases of NSCLC tissues (78.4%) compared to that in the normal controls. Reduced E-cadherin expression was significantly correlated with male smokers and squamous cell type of the cancer, but not with histological grade, TNM stage and survival. The E-cadherin expression showed a weak inverse relationship with the proliferative activity of tumor cells, which was measured using the Ki-67 antigen.

Conclusion

Our data support the hypothesis that reduced E-cadherin expression may play a role in the pathogenesis of human NSCLC, which might be associated with the control for cell proliferation.

Citations

Citations to this article as recorded by  
  • Prognostic Significance of Wnt1, Wnt2, E-Cadherin, and β-catenin Expression in Operable Non-small Cell Lung Cancer
    Anna Wrona, Aleksandra Sejda, Rafał Dziadziuszko, Jacek Jassem
    Journal of Histochemistry & Cytochemistry.2021; 69(11): 711.     CrossRef
  • Dietary flavonoid myricetin inhibits invasion and migration of radioresistant lung cancer cells (A549‐IR) by suppressing MMP‐2 and MMP‐9 expressions through inhibition of the FAK‐ERK signaling pathway
    Hye R. Kang, Jeong Y. Moon, Meran K. Ediriweera, Yeon W. Song, Moonjae Cho, Dharanibalan Kasiviswanathan, Somi K. Cho
    Food Science & Nutrition.2020; 8(4): 2059.     CrossRef
  • Patients Lung Derived Tumoroids (PLDTs) to model therapeutic response
    Frederic Delom, Inaki Begiristain, Thomas Grenier, Hugues Begueret, Fabienne Soulet, Geraldine Siegfried, Abdel-Majid Khatib, Jacques Robert, Delphine Fessart
    Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.2020; 1867(11): 118808.     CrossRef
  • Opposing role of Notch1 and Notch2 in a KrasG12D-driven murine non-small cell lung cancer model
    A Baumgart, P K Mazur, M Anton, M Rudelius, K Schwamborn, A Feuchtinger, K Behnke, A Walch, R Braren, C Peschel, J Duyster, J T Siveke, T Dechow
    Oncogene.2015; 34(5): 578.     CrossRef
  • Up-regulation of miR-9 expression as a poor prognostic biomarker in patients with non-small cell lung cancer
    T. Xu, X. Liu, L. Han, H. Shen, L. Liu, Y. Shu
    Clinical and Translational Oncology.2014; 16(5): 469.     CrossRef
  • MCAM expression is associated with poor prognosis in non-small cell lung cancer
    X. Zhang, Z. Wang, Y. Kang, X. Li, X. Ma, L. Ma
    Clinical and Translational Oncology.2014; 16(2): 178.     CrossRef
  • Transcription Regulation of E-Cadherin by Zinc Finger E-Box Binding Homeobox Proteins in Solid Tumors
    Thian-Sze Wong, Wei Gao, Jimmy Yu-Wai Chan
    BioMed Research International.2014; 2014: 1.     CrossRef
  • Prognostic Implications for High Expression of MiR-25 in Lung Adenocarcinomas of Female Non-smokers
    Fang-Xiu Xu, Yu-Liang Su, Huan Zhang, Jin-Yu Kong, Herbert Yu, Bi-Yun Qian
    Asian Pacific Journal of Cancer Prevention.2014; 15(3): 1197.     CrossRef
  • Loss of CDH1 up‐regulates epidermal growth factor receptor via phosphorylation of YBX1 in non‐small cell lung cancer cells
    Xianfang Liu, Ling Su, Xiangguo Liu
    FEBS Letters.2013; 587(24): 3995.     CrossRef
  • Podoplanin-Positive Cancer-Associated Fibroblasts Could Have Prognostic Value Independent of Cancer Cell Phenotype in Stage I Lung Squamous Cell Carcinoma
    Shotaro Ono, Genichiro Ishii, Kanji Nagai, Teruhisa Takuwa, Junji Yoshida, Mitsuyo Nishimura, Tomoyuki Hishida, Keiju Aokage, Satoshi Fujii, Norihiko Ikeda, Atsushi Ochiai
    Chest.2013; 143(4): 963.     CrossRef
  • Contactin-1 Reduces E-Cadherin Expression Via Activating AKT in Lung Cancer
    Judy Yan, Nicholas Wong, Claudia Hung, Wendy Xin-Yi Chen, Damu Tang, Jun Li
    PLoS ONE.2013; 8(5): e65463.     CrossRef
  • Wnt/β-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium
    Eugenia C. Pacheco-Pinedo, Amy C. Durham, Kathleen M. Stewart, Ashley M. Goss, Min Min Lu, Francesco J. DeMayo, Edward E. Morrisey
    Journal of Clinical Investigation.2011; 121(5): 1935.     CrossRef
  • E-cadherin but not β-catenin expression is decreased in laryngeal biopsies from patients with laryngopharyngeal reflux
    Oliver Reichel, Doris Mayr, Florian Durst, Alexander Berghaus
    European Archives of Oto-Rhino-Laryngology.2008; 265(8): 937.     CrossRef
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Expression of Cyclin-dependent Kinase Inhibitor p21(WAF1/CIP1) in Non-small Cell Lung Carcinomas: Relationship with p53 Status and Proliferative Activity
Na Hye Myong
Cancer Res Treat. 2001;33(4):329-334.   Published online August 31, 2001
DOI: https://doi.org/10.4143/crt.2001.33.4.329
AbstractAbstract PDF
PURPOSE
The objectives of this study are to elucidate the level of p21(WAF1/CIP1) expression in non-small cell lung carcinomas (NSCLCs) and to investigate the relationship between the p21(WAF1/CIP1) expression and clinicopathologic features; p53 overexpression; and proliferative activity measured by Ki-67 expression.
MATERIALS AND METHODS
The expressions of p21(WAF1/CIP1), p53, and Ki-67 proteins were analyzed by immunohistochemistry in 45 formalin-fixed and paraffin-embedded NSCLC specimens. 43 patients underwent curative resections and 2 patients had bronchoscopic biopsy specimens only. The correlations between p21(WAF1/CIP1) immunoexpression and p53 status; Ki-67 proliferative activity; and clinicopathologic parameters were analyzed statistically by chi-square or Fisher's exact test.
RESULTS
p21(WAF1/CIP1) expression in the carcinoma cells was found in 28 (62%) of 45 cases. There was no significant correlation between p21(WAF1/CIP1) expression and abnormal accumulation of p53 protein. In 16 (36%) of 45 cases, p21(WAF1/CIP1) was expressed inde pendently of p53 overexpressions. p21WAF1/CIP1 expression was not associated with patient sex, smoking history, pathological stage, tumor size, histological grade or type. However, p21WAF1/CIP1 immunoreactivity was significantly higher in older individuals over 59 years and tended to occur more intensely in the more highly differentiated portion of the squamous carcinoma. Also, a positive correlation between p21WAF1/CIP1 and Ki-67 expression was observed.
CONCLUSIONS
The present findings overall suggest that aberrations in the relationship between p21(WAF1/CIP1) and p53 expressions may be important in the development of NSCLCs; that a p53-independent pathway may be substantially involved in the induction of p21(WAF1/CIP1) expression in NSCLCs; and that the proliferative activity of lung cancers might be dependent on positive control of the cell cycle by p21(WAF1/CIP1).
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p27Kipl, K-67 and Bcl-2 Expression in Adenoid Cystic Carcinoma of Head and Neck
C S Choi, G Choi, J J Song, K S Hwang, K Y Jung, J O Choi
J Korean Cancer Assoc. 2000;32(2):382-389.
AbstractAbstract PDF
PURPOSE
p27Kip1 negatively regulates cell proliferation by mediating cell cycle arrest in Gl and Ki-67 is a reliable cellular proliferative index. Also Bcl-2, an inhibitor of apoptosis, has potential activity toward cell survival. The present study investigated p27Kip1, Ki-67 and Bcl-2 expression in adenoid cystic carcinoma for their usefulness of indicator in tumor progression and aggressiveness.
MATERIALS AND METHODS
Formalin-fixed paraffin-embedded surgical specimens were obtained from seventeen patients with adenoid cystic carcinoma. We performed immunohistochemical staining with p27Kip1, Ki-67 and Bcl-2 monoclonal antibodies and compared with patients clinicopathologic features.
RESULTS
There were significant correlation between low p27Kip1 expression and high grade and T classification, positive nodal status and perineural invasion and high stages. However, Ki-67 and Bcl-2 expression had no significant differences in clinicopathologic features and p27Kip1 expression.
CONCLUSION
p27Kip1 is a good reliable marker of tumor progression and aggressiveness in adenoid cystic carcinomas.
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p 53 Expression in Non - Small Cell Lung Cancer: Its relationship to the clinical prognostic factor and smoking history
Moon Kyung Kim, Han Kyeom Kim, In Sun Kim, Joung Ho Han, Seung Jae Huh, Yong Chan Ahn, Dae Yong Kim, Young Mok Shim
J Korean Cancer Assoc. 1999;31(6):1219-1226.
AbstractAbstract PDF
PURPOSE
p53 mutations are one of the most common genetic alterations in human lung cancer. Although the prognostic value of mutant p53 is still debated, it is widely accepted as a relatively early genetic event in the development and progression of lung cancer. Moreover, there are growing reports about an association between smoking and p53 mutation, suggesting that the p53 gene could be a target of the smoking associated carcino- genesis in the lung cancer.
MATERIALS AND METHODS
Surgically resected 89 primary non-small cell lung cancers were obtained from May of 1995 to May of 1997. p53 expression and Ki-67 expression were measured by immunohistochemistry, and each p53 expression and smoking amount were compared with Ki-67 expression and other clinical prognostic factors.
RESULTS
Positive p53 expressions were found in 52 (58%) specimens, including 38 (69%) squamous cell carcinomas, 11 (39%) adenocarcinomas, and 3 (50%) large cell carcinomas, and closely associated with male and squamous cell carcinoma. Also close correlation was observed between smoking amount and p53 expression by the regression analysis. But p53 and Ki-67 expression showed no associations in pathologic stage and survival, and there was no association between p53 expression and survival after adjuvant radiotherapy.
CONCLUSION
Smoking seems to affect p53 mutations in non-small cell lung cancer, and additional efforts are needed to evaluate the carcinogesis of lung cancer.
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Prognostic Significance of p53, c-erbB-2, nm23 and Ki-67 Expression in Patients with Advanced Gastric Carcinoma
Sung Hoon Noh, Chang Hak Yoo, Ho Gune Kim, Young Ha Oh, Jin Sik Min
J Korean Cancer Assoc. 1999;31(4):699-709.
AbstractAbstract PDF
PURPOSE
We investigated the prognostic impacts of p53, c-erbB-2, nm23 and Ki-67 expression in patients with stage II and IIIA gastric carcinoma who underwent curative (RO) resections.
MATERIALS AND METHODS
261 paraffin-embedded gastric carcinoma tissues (stage II, 121; stage IIIA, 135) were stained with the monoclonal antibodies, p53, c-erbB-2, nm23 and Ki-67 using the labelled streptovidin biotin method. The positivity was determined by two pathologists who were kept blind for the patients outcome.
RESULTS
The overexpression was seen in 51.7% for p53, 11.9% for c-erbB-2, and 70.1% for nm23. The mean Ki-67 labelling index was 25.5+ 16.7. The rates of overexpression between the stage II and stage IIIA were not significantly different in all these molecules. Overexpression of p53 was more likely to be associated with old age and lymph node metastasis. Overexpression of c-erbB-2 was more likely to be associated with Borrmann type I, II and well-differentiated tumor. However, nm23 was more frequently expressed in patients with older age and well-differentiated tumor. In survival analysis, the overexpressions of p53 and Ki-67 were significantly associated with poor prognosis of the patients (p<0.01), but c-erbB-2 and nm23 were not related to the patients outcome. In a multivariate analysis of prognostic factors, only. the lymph node metastasis was an independent prognostic factor.
CONCLUSION
Although the values did not reach statistical significance in a multivariate analysis, the overexpression of p53 and Ki-67 tended to have adverse effects an the prognosis of patients with gastric cancer.
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Expression Pattern of Ki-67 and Apoptosis in Low grade Adenoma of Stomach and Colon
Jae Kyu Lee, Ki Jung Yun, Hyung Bae Moon
J Korean Cancer Assoc. 1999;31(2):411-417.
AbstractAbstract PDF
PURPOSE
Gastrointestinal carcinomas usually evolve through a series of well defined histologic steps. This concept of carcinogenesis is a multistep process involving progressive loss of growth control as well as an expansion and shift of cell proliferation. The cell proliferations and kinetics of normal gastrointestinal tract are well known. But, the cell kinetics of adenoma in gastrointestinal tract is poorly understood. This study was designed to evaluate the cell kinetics of low grade adenoma in stomach and colon.
MATERIALS AND METHODS
The study was carried by the TUNEL method for the apoptosis and immunohistochemical staining for the Ki-67 using the formalin fixed paraffin embedded tissues.
RESULTS
The mucosal locations of apoptotic cells and Ki-67 immunoreactive cells were irregular in gastric adenoma. The Ki-67 immunoreactive ceils were located in the base of colonic adenoma. Apoptotic cells were located in the luminal surface of the colonic adenoma, CONCLUSION: Above results indicate that most cells of the colonic adenoma move toward the lumen, corresponding to the base and lumen in low grade adenoma of stomach.
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DNA Content and Ki - 67 Antibody Expression by Means of Image Analyzer for Laryngeal Lesions
Hyung Ro Chu, Sun Hee Lee, Jong Ouck Choi, In Sun Kim
J Korean Cancer Assoc. 1994;26(3):466-474.
AbstractAbstract PDF
The laryngeal epithelial cell kinetics of 26 laryngeal lesions(invasive squamous cell carcinoma 14, epithelial hyperplasia 5, laryngeal nodule 7) were studied by immunohistochemical analysis with the monoclonal antibody Ki-67, which reacts with a nuclear antigen in proliferating cells using paraffin embedded tissue. For DNA analysis, touch imprint with fresh biopsy specimens were stained with Feulgen and analyzed by image analyzer in 22 cases. 1) The positive nuclear area of Ki-67 were 32.65+-11.59% in invasive squamous cell carcino- ma, 20.14 +- 3.38% in epithelial hyperplasia and 11.66+ 3.02% in laryngeal nodule. 2) DNA aneuploidy was found in 7 cases of 10(70%) invasive squamous cell carcinomas, 2 cases of 5(40%) epithelial hyperplasia and none of laryngeal nodules. 3) Average proliferative index(S phasa+ G2/M phase) was 24.32+- 1l.33% in spuamous cell carcinama, 13.09 +- 10.90% in epithelia1 hyperplasia and 4.50 +- 1.19% in laryngeal nodule. As the results, the measurement of the DNA content and Ki-67 positive nuclear area on the small biopsy obtained by microscopic surgery used as effective factors predicting prognosis.
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Effects of Retinoic Acid on p53 Protein , Ki - 67 and PCNA / Cyclin Expression in PLC / PRF / 5 Cells
Dae Gon Kim, Cheol Kwon, Wan Hee Yoo, Yee Yup Kim, Deuk Su Ahn
J Korean Cancer Assoc. 1995;27(4):559-570.
AbstractAbstract PDF
Retinoic acid(RA), known to have antiproliferative and differentiation-inducing effecte on cancer cells, was examined to evaluate its potential as a chemotherapeutic agent for hepatocellular carcinoma. The treatment of PLC/PRF/5 cells with RA(l0 pM for 8 days)resulted in inhibited growth by 23.8% as compared to that of control. The decreased cell growth rate was started 2 days after RA addition. We examined the level of expressions of the mutated p53 protein, the Ki-67 antigen, and the proliferation cell nuclear antigen(PCNA)in cultured PLC/PRF/5 hepatocelluar carcinoma cells before and after RA treatment. The mutated pM is thought to be involved in oncogenesis of human cancers, and the expressions of the Ki-67 and the PCNA are used to evlauate tumor cell kinetics. The e#xpression of p53 protein was not inhibited significantly in PLC/PRF/5 cells by treatment with 10 M RA in Go/Gi, S, or G/M phase fraction, as detected by immunocytochemical staining using the monoclonal antibody PAb 180 which recognizes both the wild and the mutated p53 protein. Also no significant increase of expression was observed using the monoclonal antibody PAb 240 which binds only the mutated p53 protein. RA treatment increaaed Go unstained fraction from 0.36+-0.06% to 0.7+-0.19% and decreased Ki-67 antigen expresaion significantly from 51.2+0.8% to 46.9+0.4%(p=0.03) in G phase, 14.8 0.5% to 1l.30.5%(p=0.03) in S phase respectively, but increased the fraction of GgM phase from 33.4+-1.1% to 36.8+-1.4%(p=0.02). PCNA expression was also dropped by RA treatment from 50.4+-1.5% to 42.8+-0.3%(p=0.01) in Gw G, fraction, 14.7+-0.5% to 11.9+-0.4%(p=0.02) in S phase, increased G/M phase fraction from 31.3+-l.2% to 42.2+-0.6%(p=0.008). These results suggested that RA may have anticancer effect through the inhibitiion of Ki-67 and PCNA expression in similar cell cycle phase without affecting the expression of mutant p53 protein in PLC/PRF/5 cells was observed. In addition, cell cycle anaysis suggested that RA induced en arrest of G, progression to G, and S phase.
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Significance of Cathepsin D as a Prognostic Factor of Breast Cancer
Dong Wha Lee, Dong Won Kim, So Yeung Jin
J Korean Cancer Assoc. 1996;28(2):261-272.
AbstractAbstract PDF
Cathepsin D(CD) is an intralysosomal aspartyl protease that is important in the pracess of breast carcinoma invasion and metastases by virtue of its proteolytic function, degradation of extracellular matrix, and tumar cell proliferation. Some studies have found significant correlations between increased tumor CD levels and reduced disease-free and overall survival. Other studies, however, have not found a consistent association between CD expression and prognosis. Immunohistochemical staining with Ki-67 monoclonal antibody is the best method to measure cell proliferation in breast carcinoma and its relationship to prognosis. To investigate a prognostic utility of CD and Ki-67 proliferating index(MIB-1) in breast carcinoma, 50 cases of breast carcinoma were studied for CD expression and Ki-67 proliferating index and compared them to other prognostic factors, such as estrogen receptor status, lymph node status, nuclear grade, tumor size, and mean microvessel density. Immunohistochemical staining was performed on 50 formalin-fixed, paraffin-embedded breast carcinoma tissues using a standard avidin-biotin complex method with CD(Dako) and MIB-l(Immunotech). In our series of breast carcinoma, overall CD expression was <10 % in 17 cases (34%) and was >10% in the remaining 33 cases (66%). The percentage of total CD-positive cells contributed by carcinoma cells (percent carcinoma) was <50% in 36 (72% and >50% in 14 (28%), and the percentage contributed by stromal elements(percent stroma) was >10% in 43 cases (86%). The percentage of MIB-1 expression was 0% in 5 cases, <10% in 18 cases, 10-50% in 22 cases, and >5% in 5 cases. These results showed that increased stromal CD expression significantly correlated with high nuclear grade (p< 0.05), and increased overall and carcinoma CD expression significantly correlated with tumor size (p<0.05 and p<0.02). CD expression tended to be increased in positive lymph node status, but not significant. The correlation between increased CD expression and MIB-1 proliferating index did not reach statistical significance, but there were trends to increased CD expression with increased MIB-1 proliferating index. All other prognostic factors, such as estrogen receptor status, lymph node status, and mean microvessel density, are not related with CD expression. According to these findings, a prognostic utility of CD in breast carcinoma is limited to a few prognostic factors of nuclear grade and tumor size.
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