The clinical implications of MMP-11 and CK-20 expression in human breast cancer.
BACKGROUND
Tumor invasiveness and metastasis in cancer progression is manifested by epigenetic abnormality. However, it remains unknown whether transcription regulation of matrix metalloproteinase-11(MMP-11) and cytoskeleton-20 (CK-20) genes for the homoeostasis of epithelial/connective interface that can enhance cell dissemination and invasion may act as alternative mutators to tumor clinicopathology.


METHODS
Paired cancerous and tumor-adjacent normal tissues from 72 breast cancer patients were assayed for the expression of MMP-11 and CK-20 by using real-time RT-PCR. The expression profiles were evaluated for the association with clinicopathological factors.


RESULTS
Breast tumor tissues displayed higher expression levels of MMP-11 and CK-20 than those of the adjacent non-cancerous tissues. Overexpression of either MMP-11 or CK-20 correlated with patients having poorly differentiated tumors (P(MMP-11)=0.01 and P(CK-20)=0.05) and lymph node metastasis (LNM) (P(MMP-11)=0.004 and P(CK-20)=0.001). A synergistic effect between MMP-11 and CK-20 on risk elevation was significant in patients with advanced tumor stage (OR=2.03, 95%CI=1.10-3.77) and LNM (OR=2.83, 95%CI=1.20-4.71). Additionally, patients lacking progesterone receptor exhibited high expression of MMP-11 and CK-20.


CONCLUSIONS
We demonstrate that MMP-11 and CK-20 are probable prognostic markers whose expression reflects the stages of tumor differentiation and LNM of breast cancer.
Cheng
Chun-Wen
CW
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan. cwcheng@csmu.edu.tw
Yu
Jyh-Cherng
JC
Wang
Hsiao-Wei
HW
Huang
Chiun-Sheng
CS
Shieh
Jia-Ching
JC
Fu
Yi-Ping
YP
Chang
Chia-Wei
CW
Wu
Pei-Ei
PE
Shen
Chen-Yang
CY
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D053554:Keratin-20 / Q000235:genetics*; D008207:Lymphatic Metastasis / Q000235:genetics; D053507:Matrix Metalloproteinase 11 / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
D000906:Antibodies; D014408:Biomarkers, Tumor; D053554:Keratin-20; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D053507:Matrix Metalloproteinase 11