Cancer Research and Treatment

Original Articles

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

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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.

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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; 27(1): 126. CrossRef
Downregulation of MTHFD2 Inhibits Proliferation and Enhances Chemosensitivity in Hepatocellular Carcinoma via PI3K/AKT Pathway
Jie Wang, Ze Yu, Yixiao Jiang, Ting Le, Yixin Wu, Ziqi Li, Guoqiang Zhang, Feiyue Wu, Haijie Ma
Frontiers in Bioscience-Landmark.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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Osteopontin, CD44, and NFκB Expression in Gastric Adenocarcinoma: Jung Yeon Kim, Byung-Noe Bae, Kyoung Soo Kim, Eunah Shin, Kyeongmee Park; Cancer Res Treat. 2009;41(1):29-35. Published online March 31, 2009; DOI: https://doi.org/10.4143/crt.2009.41.1.29

Abstract PDF PubReader ePub

Purpose

Osteopontin (OPN) binds to CD44 and nuclear factor-κB (NFκB) and OPN mediates tumorigenesis, invasion and metastasis, but the interrelationships between OPN, CD44 and NFκB are not fully understood, and especially in gastric carcinogenesis. We examined the expressions of OPN, CD44, and NFκB in untreated gastric adenocarcinomas.

Materials and Methods

The materials from 211 cases of gastric adenocarcinoma were immunostained for OPN, CD44 and NFκB by using a tissue microarray. The OPN mRNA expression was measured in 10 cases by performing real-time RT-PCR.

Results

The expression of OPN, CD44 and NFκB was noted in 61.7%, 11.4% and 26.6% of the adenocarcinoma tissues, respectively. No significant correlation was detected among the expressions of these proteins. The OPN protein expression was negatively correlated with angioinvasion (p<0.05) and patient survival (p<0.05), whereas the CD44 and NFκB protein expressions were not correlated with any of the clinicopathological factors we examined. The depth of invasion, lymph node status and perineural invasions were prognostic factors based on the Cox analysis. The OPN mRNA expression showed no significant difference between the adenocarcinoma and the paired normal mucosa on real-time RT-PCR.

Conclusion

OPN may have a currently undetermined role in gastric carcinogenesis, and CD44 and NFκB may have minor roles in gastric adenocarcinoma.

Citations

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Osteopontin Splicing Isoforms Contribute to Endometriotic Proliferation, Migration, and Epithelial-Mesenchymal Transition in Endometrial Epithelial Cells
Nguyen-Tuong Ho, Shu-Wei Lin, Yi-Rong Lee, Chii-Ruey Tzeng, Shu-Huei Kao
International Journal of Molecular Sciences.2022; 23(23): 15328. CrossRef
CD44: A Multifunctional Mediator of Cancer Progression
Malak Hassn Mesrati, Saiful Effendi Syafruddin, M. Aiman Mohtar, Amir Syahir
Biomolecules.2021; 11(12): 1850. CrossRef
Cyclooxigenase-2 and osteopontin in gastric pre-neoplastic lesions in relation to H-pylori infection and grade of inflammation
Inés Benedetti, Julián Hoyos, Lía Barrios
Revista Española de Patología.2020; 53(2): 79. CrossRef
Prognostic Value of Cyclin D1 and CD44 Expression in Gastric Adenocarcinoma
Hanaa M. Ibrahim, Abeer M. AbdElbary, Salem Y. Mohamed, Amira Elwan, Mohamed I. Abdelhamid, Amr Ibrahim
Journal of Gastrointestinal Cancer.2019; 50(3): 370. CrossRef
Osteopontina, una proteína involucrada en la progresión tumoral, y su participación en el desarrollo del carcinoma colorrectal.
Daniel Becerra, Ines Benedetti
Revista Ciencias Biomédicas.2019; 8(1): 15. CrossRef
Prognostic value of osteopontin in patients with hepatocellular carcinoma
Tingting Sun, Peng Li, Diwen Sun, Qingao Bu, Guoqiang Li
Medicine.2018; 97(43): e12954. CrossRef
Expression of TWIST1 and CD44 as diagnostic and prognostic biomarkers in patients with gastric cancer
Marwa A. El Kholy, Hala A. El Sayed, Eman M. Ahmed
The Scientific Journal of Al-Azhar Medical Faculty, Girls.2018; 2(3): 163. CrossRef
Osteopontin at the Crossroads of Inflammation and Tumor Progression
Luigi Mario Castello, Davide Raineri, Livia Salmi, Nausicaa Clemente, Rosanna Vaschetto, Marco Quaglia, Massimiliano Garzaro, Sergio Gentilli, Paolo Navalesi, Vincenzo Cantaluppi, Umberto Dianzani, Anna Aspesi, Annalisa Chiocchetti
Mediators of Inflammation.2017; 2017: 1. CrossRef
Gastric cancer stem cells: evidence, potential markers, and clinical implications
Daniel Brungs, Morteza Aghmesheh, Kara L. Vine, Therese M. Becker, Martin G. Carolan, Marie Ranson
Journal of Gastroenterology.2016; 51(4): 313. CrossRef
Clinicopathological and prognostic significance of cancer stem cell markers CD44 and CD133 in patients with gastric cancer
Li Lu, Menglin Wu, Longhao Sun, Weidong Li, Weihua Fu, Xuening Zhang, Tong Liu
Medicine.2016; 95(42): e5163. CrossRef
Prognostic significance of osteopontin expression in gastric cancer: a meta-analysis
Xiaobin Gu, Xian-Shu Gao, Mingwei Ma, Shangbin Qin, Xin Qi, Xiaoying Li, Shaoqian Sun, Hao Yu, Wen Wang, Dong Zhou
Oncotarget.2016; 7(43): 69666. CrossRef
The impact of osteopontin on prognosis and clinicopathology of colorectal cancer patients: a systematic meta-analysis
Mingfei Zhao, Feng Liang, Buyi Zhang, Wei Yan, Jianmin Zhang
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Ablation of osteopontin suppressesN-methyl-N-nitrosourea andHelicobacter pylori-induced gastric cancer development in mice
Su-Hyung Lee, Jun-Won Park, Du-Min Go, Hark Kyun Kim, Hyo-Jung Kwon, Sang-Uk Han, Dae-Yong Kim
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Control of the Human Osteopontin Promoter by ERRα in Colorectal Cancer
Salah Boudjadi, Gérald Bernatchez, Jean-François Beaulieu, Julie C. Carrier
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Jiheum Paek, San-Hui Lee, Ga-Won Yim, Maria Lee, Young-Jae Kim, Eun-Ji Nam, Sang-Wun Kim, Young-Tae Kim
European Journal of Obstetrics & Gynecology and Reproductive Biology.2011; 158(2): 338. CrossRef
CD44-SLC1A2 Gene Fusions in Gastric Cancer
Jiong Tao, Nian Tao Deng, Kalpana Ramnarayanan, Baohua Huang, Hue Kian Oh, Siew Hong Leong, Seong Soo Lim, Iain Beehuat Tan, Chia Huey Ooi, Jeanie Wu, Minghui Lee, Shenli Zhang, Sun Young Rha, Hyun Cheol Chung, Duane T. Smoot, Hassan Ashktorab, Oi Lian Ko
Science Translational Medicine.2011;[Epub] CrossRef

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The Serum Assay of Soluble CD44 Standard, CD44 Variant 5, and CD44 Variant 6 in Patients with Gastric Cancer: Chang Hak Yoo, Sung Hoon Noh; Cancer Res Treat. 2003;35(1):3-8. Published online February 28, 2003; DOI: https://doi.org/10.4143/crt.2003.35.1.3

Abstract PDF

PURPOSE
Alternative splicing of CD44 and aberrant levels of soluble CD44 (sCD44) protein in the serum of cancer patients has been correlated to tumor progression and metastasis. The purpose of this study was to evaluate the concentrations, and the prognostic potential of sCD44s, sCD44v5 and sCD44v6, in patients with gastric cancer. MATERIALS AND METHODS: The serum levels of sCD44s, sCD44v5 and sCD44v6 were determined quantitatively using an enzyme-linked immunosorbent assay. Serum samples were obtained from 116 patients with gastric cancer, both before and after surgery, and from 30 healthy controls. RESULTS: The serum sCD44v6 levels were significantly higher in patients with gastric cancer than in the healthy controls, whereas those of sCD44s and sCD44v5 were no different. The surgical resection of the tumor resulted in a significant reduction in all the sCD44 proteins, whereas if a surgical resection was not performed the concentrations of the sCD44v5 and sCD44v6 were not reduced prior to surgery. The serum sCD44v6 levels correlated with the venous or lymphatic invasion of the tumor and lymph node metastasis. In addition, a high preoperative serum sCD44v6 level was significantly associated with poor prognosis in patients with gastric cancer. CONCLUSION: The preoperative serum level of sCD44v6 in patients with gastric cancer was significantly higher than that in the healthy controls, and correlated with the venous or lymphatic invasion of the tumor and lymph node metastasis. In addition, a high preoperative serum sCD44v6 level was significantly associated with poor prognosis in patients with gastric cancer. These results suggest that an elevation of the serum sCD44v6 level might be used as a new predictor of tumor invasiveness, and poor prognosis, in patients with gastric cancer.

Citations

Citations to this article as recorded by

Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer
Jie Yang
Medical Oncology.2020;[Epub] CrossRef
Breast Cancer Cell–Derived Soluble CD44 Promotes Tumor Progression by Triggering Macrophage IL1β Production
Jeong-Hoon Jang, Do-Hee Kim, Jae Min Lim, Joon Won Lee, Su Jin Jeong, Kwang Pyo Kim, Young-Joon Surh
Cancer Research.2020; 80(6): 1342. CrossRef
BRCA1 and BRCA2 germline mutations in Korean ovarian cancer patients
Myong Cheol Lim, Sokbom Kang, Sang-Soo Seo, Sun-Young Kong, Bo-Yon Lee, Seon-Kyung Lee, Sang-Yoon Park
Journal of Cancer Research and Clinical Oncology.2009; 135(11): 1593. CrossRef
Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance
Kamran Ghaffarzadehgan, Mostafa Jafarzadeh, Hamid Reza Raziee, Hamid Reza Sima, Ehsan Esmaili-Shandiz, Hanieh Hosseinnezhad, Ali Taghizadeh-Kermani, Omeed Moaven, Maryam Bahrani
World Journal of Gastroenterology.2008; 14(41): 6376. CrossRef

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Immunohistochemical Study for CD44v6 in Hepatocellular Carcinoma and Cholangiocarcinoma: Ki Jung Yun, Kwon Ha Yoon, Weon Cheol Han; Cancer Res Treat. 2002;34(3):170-174. Published online June 30, 2002; DOI: https://doi.org/10.4143/crt.2002.34.3.170

Abstract PDF

PURPOSE
CD44 is a multifunctional adhesion molecule in cell-to-cell and cell-to-matrix interactions. This transmembrane glycoprotein exists in either standard or variant form, with the variation originating in alternative splicing. This study was designed to evaluate the role of CD44v6, one of the CD44 isoforms, in hepatocellular carcinoma and cholangiocarcinoma. MATERIALS AND METGODS: Immunohistochemical expression of CD44v6 was studied in 7 normal livers, 14 hepatocellular carcinomas and 16 cholangiocarcinomas, that were formalin fixed and paraffin embedded.
RESULTS
CD44v6 was frequently expressed in the normal hepatocytes and hepatocellular carcinomas. Expression was not noted in the normal bile duct within the portal tract. CD44v6 was positively expressed in some of the proliferating bile ducts (43%) and cholangiocarcinomas (69%).
CONCLUSION
CD44v6 expression may be more important in the stepwise carcinogenesis of the bile duct than in the normal hepatocyte, but further study is needed.

Citations

Citations to this article as recorded by

Impact of Alternative Splicing Variants on Liver Cancer Biology
Jose J. G. Marin, Maria Reviejo, Meraris Soto, Elisa Lozano, Maitane Asensio, Sara Ortiz-Rivero, Carmen Berasain, Matias A. Avila, Elisa Herraez
Cancers.2021; 14(1): 18. CrossRef
Aberrant mRNA splicing generates oncogenic RNA isoforms and contributes to the development and progression of cholangiocarcinoma (Review)
Juthamas Yosudjai, Sopit Wongkham, Siwanon Jirawatnotai, Worasak Kaewkong
Biomedical Reports.2019;[Epub] CrossRef
An aberrantly spliced isoform of anterior gradient-2, AGR2vH promotes migration and invasion of cholangiocarcinoma cell
Juthamas Yosudjai, Chaturong Inpad, Sasitorn Chomwong, Paweena Dana, Kanlayanee Sawanyawisuth, Suchada Phimsen, Sopit Wongkham, Siwanon Jirawatnotai, Worasak Kaewkong
Biomedicine & Pharmacotherapy.2018; 107: 109. CrossRef
Prognostic Significance of CD44s Expression in Biliary Tract Cancers
Sang Min Lee, Kyoung Eun Lee, Hye Jung Chang, Moon Young Choi, Min-Sun Cho, Seog Ki Min, Hyeon Kook Lee, Yeung Chul Mun, Eun Mi Nam, Chu Myong Seong, Soon Nam Lee
Annals of Surgical Oncology.2008; 15(4): 1155. CrossRef

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Expression of CD44 Standard, Variant 6 and Relationship to the Lymph Node Metastasis in Gastric Adenocarcinoma: Joo Ho Lee, Hang Jong Yu, Byung Jo Suh, Mee Ju, Hae Kyung Lee, Jin Pok Kim; J Korean Cancer Assoc. 2000;32(4):665-673.

Abstract PDF: PURPOSE
The transmembrane glycoprotein CD44 exists in a variety of isoforms generated by alternative splicing of the pre-mRNA. We studied the role of CD44-standard (CD44s) and CD44-variant6 (CD44v6) in gastric adenocarcinoma.
MATERIALS AND METHODS
Immunohistochemical staining was performed in 101 patients with gastric adenocarcinoma who underwent radical gastrectomy at KGCC, Seoul Paik Hospital. The relationship of CD44s, CD44v6 expressions to the clinicopathologic parameters, p53 and Ki-67 were evaluated.
RESULTS
CD44s and CD44-v6 expressions were found in 56.4% and 48.5%, respectively. CD44s expression was significantly correlated with lymph node metastasis, lymphatic invasion, and Borr mann type. CD44v6 expression was significantly correlated with sex, lymph node metastasis, lymphatic invasion, and perineural invasion and had a tendency toward p53 expression. In inte stinal type adenocarcinoma, CD44s expression had correlations with lymph node metastasis and CD44v6 had correlations with lymph node metastasis, lymphatic invasion. However, in diffuse type adenocarcinoma, CD44s and CD44v6 expressions had correlations with only Borrmann type. In multivariate analysis, lymph node metastasis was the most significant risk factor for CD44s and CD44v6 expressions in total cases and intestinal type adenocarcinoma.
CONCLUSION
These data suggest that expression of CD44 v6 may play an important role in the regulation of lymph node metastasis in intestinal type adenocarcinoma of stomach.

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The Clinical Value of CD44 in Gastric Cancer: Kyung Ho Ryu, Hyung Chul Kim, Moo Jun Baek, Ok Pyung Song, Chang Jin Kim; J Korean Cancer Assoc. 1999;31(5):921-930.

Abstract PDF: PURPOSE
This research was performed to investigate the relationship between CD44 and cancer cell invasion depth, histologic differentiation, tumor size and lymph node metastasis in the gastric carcinoma.
MATERIALS AND METHODS
In 20 cases of early gastric cancer and 40 cases of advanced gastric cancer, the immunohistochemical staining for CD44v3 and CD44v5 was performed.
RESULTS
1. In all 60 cases, the positive rates for CD44v3 and CD44v5 were 18.3% and 71.7% respectively. 2. CD44v5 was expressed in 45% of early gastric cancer and 85% of advanced gastric cancer. 3. Larger tumor exhibited higher positive rates for CD44v5. 4. There were 28 cases of lymph node metastases out of 43 cases of CD44v5-positive primary gastric carcinoma (65.1%), and were 4 cases of lymph node metastases out of 17 CD44v5-negative cases (23.5%). 5. The 5 year survival rate was low in CD44v5- positive cases (p-value=0.039).
CONCLUSION
The tumors that exhibit deep invasion and have large size and lymph node metastases tend to have more frequent expression of CD44v3 and CD44v5. In especially CD44v5. We found a good correlation between he expression of CD44v5 and the established prognostic factors. Actually we can use the CD44v5 rather than CD44v3 as a prognostic factor in advanced gastric cancer.

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The Expression of c-erbB-2 and CD44 Gene in Breast Cancer: Jun Heyoung Heo, Yong Gui Kim, Sung Hyuk Kim, Jai Hak Lee; J Korean Cancer Assoc. 1998;30(6):1119-1130.

Abstract PDF: PURPOSE
There are some controversial opinions on the prognostic value of metastasis- associated tumor markers in breast cancer. Out of them, the overexpression of c-erbB-2 proto-oncogene or CD44 gene has been debated on their activities in promoting metastatic potential.
MATERIALS AND METHODS
To detennine the relationship between expression of these genes, and, clinicopathological parameters and disease outcomes including relapse and survival, 48 archival paraffin-embeded breast-cancer tissues were stained using monoclonal antibody against each gene product by immunohistochemical staining method, and the result was analyzed.
RESULTS
The positive expression rates of c-erbB-2 and CD44 genes were 45.8% and 18.8%, respectively. The expression rates of both genes were 14.6% and 50% of cases showed no expression of either gene. Except the statistically significant positive correlation between CD44 and tumor size (P=0.003), the expression of c-erbB-2 or CD44 expression had no significant relationship with tumor size, stage, lymph node status, and disease recurrence (P>0.05). In the positive expression cases for CD44, disesase-free survival (DFS) and overall survival (OS) in months were shorter than the negative ones (53+/- 8 vs. 64+/-5 and 67+/-8 vs. 77+/-5 S.E.). And, the c-erbB-2 positive cases had longer OS than the negative ones (78+/- 6 vs. 71+/- 6). The OS of positive co-expression cases with the c-erbB-2 and CD44 was shorter than that of one-gene expression ones (66+/- 6 vs. 75+/-7). Thus the OS result observed in the expression of c-erbB-2 alone was reversed in the co-expression study. Though these results had no statistically significant level (P> 0.05).
CONCLUSION
We suggest a question if there is any interaction or dependency between c-erbB-2 and CD44 expression in view of disease process including OS. Finally, further randomised controlled studies are advisable for the reproducible and significant results.

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Expression of CD44 Splice Variant mRNA in Bladder Cancers and its Diagnostic Application: Min Ho Suh, Won Ki Baek, Jong Wook Park, Chun Il Kim, Min Ho Suh, Byung Kil Choe; J Korean Cancer Assoc. 1995;27(3):451-459.

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Prognostic Signicance of the CD44 and Matrix Metalloproteinase 3 ( Stromelysin 3 ) Expression in Breast Cancer: Hye Rim Park, Jin Hee Sohn, Young Euy Park; J Korean Cancer Assoc. 1995;27(4):593-602.

Abstract PDF: Expression of the CD44 and matrix metalloproteinase 3 were examined in 43 cases of breast carcinoma. Immunohistochemical staining with CD44 antibodies demonstrated dif- fuse cytoplasmic positivity in tumor cells of intraductal and invasive carcinoma. Matrix metalloproteinase 3 was present in invasive cancer cells and surronding stromal cells. Expression of the CD44 and matrix metalloproteinase 3 were moderately correlated. Expression of the CD44 was associated with the large size of primary tumor(>=2cm), the histologic grade by Bloom-Richardson, the presence of metastatic node, and the clinical stage. Overall five-year survival rate in 43 patients was 74.0+-9.6% and the disease free survival curve showed significant difference according to the expression of CD44. However, the expression of matrix metalloproteinase 3 was not associated with variable prognostic factors and disease free survivaL From this study, it is concluded that expression of the CD44 and matrix metalloproteinase 3 were associated with invasion of breast cancer and expression of the CD44 could be used as a prognostic indicator in breast cancers. However, the expression of matrix metal- loproteinase 3 had the limited value.

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