The Utility of Matrix Metalloproteinase-2 and TIMP-2 as tumor markers in cervical cancer

Park, Dong Choon; Yoo, Jin Young; Lew, Young Ok; Kim, Dae Hoon

Abstract

OBJECTIVE
The disintegration of extracellular matrix and basement membrane are important processes in the infiltration and metastasis of malignant tumors. We investigated the expressions of matrix metallo- proteinase-2 (MMP-2) and tissue inhibitors of metalloproteinases (TIMP-2) in tissues and sera from patients with cervical cancer, and compared the expressions of these enzymes with patient clinical status to determine the possibility of these enzymes being used as tumor biomarkers.
METHODS
: The expressions of MMP-2 and TIMP-2 were investigated in sixty cervical cancer tissues obtained from patients who were histologically confirmed having cervical cancer by immunohistochemical staining, and the expressions of the mRNAs of MMP-2 and TIMP-2 were confirmed by using RT-PCR. Also, the amounts of MMP-2 and TIMP-2 in sera obtained from each patient during treatment progress were measured using ELISA to determine the presence of a relationship between the expression levels of these enzymes and the clinical condition of the patient.
RESULTS
In terms of the expression levels of MMP-2 and TIMP-2 by immunohistochemical staining, MMP-2 was shown to be positive in 46% (28/60) of the normal cervical tissues and in 75% (45/60) of the cervical cancer tissues, and the degree of expression of MMP-2 was also stronger in cervical cancer tissue than in normal cervical tissue. TIMP-2 was shown to be positive in 23% (14/60) and 27% (16/60) of normal cervical tissues and cervical cancer tissues, respectively, though these expressions were weak in nature. The mRNA of MMP-2 was more distinctly expressed in cervical cancer tissue than normal cervical tissue, but no difference could be seen in the case of TIMP-2. In terms of expressions as determined by ELISA, the positivity rate of MMP-2 in the normal control group and the cervical cancer group were 12% (7/54) and 76% (46/60), respectively, and the corresponding positivity rates of TIMP-2 were 22% (12/54) and 98% (59/60), respectively (p<0.05). MMP-2 expression reflected clinical condition in 57.5% of the patients, and TIMP-2 in 35%, however, MMP-2 expression increased in the presence of recurrent cervical cancer.
CONCLUSIONS
: MMP-2 and TIMP-2 are closely related with cervical cancer, and MMP-2 is believed a tumor biomarker that possibly reflects clinical status.