Clinical significance of matrix metalloproteinase-2 in cancer of uterine cervix: a semiquantitative study of immunoreactivities using tissue array.
OBJECTIVE
To study the expression of matrix metalloproteinase-2 (MMP-2) in cancer of uterine cervix and correlate its expression with clinicopathological parameters, recurrence and survival of patients.


METHODS
Twenty cervical cancer and 20 normal tissues from the same patients were collected to detect MMP-2 mRNA expression. From them, 16 cancer and 16 normal tissues were collected and added with another 64 cancer tissues to construct a 96-tissue core microarray for immunohistochemical study. We evaluated the relationships among MMP-2 immunoreactivity using semiquantitative H scores, obtained by multiplying proportion score of stained cells and their mean digital density, and clinicopathological variables, recurrence and survival in cervical cancer patients. We used univariate and multivariate analyses of all parameters for recurrence and survival, further including time interval for evaluation.


RESULTS
MMP-2 mRNA expression was higher in most of cervical cancerous tissues than normal counterparts. H score of MMP-2 was significantly higher in cancerous tissue cores than normal counterparts (median H scores: 1.5 vs. 0.3, P<0.001). MMP-2 expression was significantly associated with parametrium invasion (P=0.004) and lymph node metastasis (P=0.015), but not with cancer recurrence, recurrence-free and overall survival rates of these patients. However, poor tumor cell differentiation and positive parametrium invasion significantly increased the recurrence and poor cell differentiation increased the risk of death.


CONCLUSIONS
MMP-2 is highly expressed in cervical cancer tissues at mRNA and protein levels and associated with lymph node metastasis and parametrium invasion but not predictive of recurrence and survival in cervical cancer patients.
Wang
Po-Hui
PH
Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, 110, Section 1, Chien-Kuo North Road, Taichung, 40201, Taiwan.
Ko
Jiunn-Liang
JL
Tsai
Hsiu-Ting
HT
Yang
Shun-Fa
SF
Han
Chih-Ping
CP
Lin
Long-Yau
LY
Chen
Gin-Den
GD
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D016022:Case-Control Studies; D017931:DNA Primers; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016019:Survival Analysis; D013624:Taiwan; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality
D017931:DNA Primers; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2