Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer.
BACKGROUND
Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may therefore play an essential role in the progression of a malignant tumour.The primary aim of the present study was to evaluate TIMP-1 protein immunoreactivity in tissue from primary ovarian cancer patients and associate these findings with the course of the disease including response to treatment in the individual patient.


METHODS
TIMP-1 was assessed by immunohistochemistry (in tissue micro arrays) in a total of 163 ovarian cancer specimens obtained from primary debulking surgery during 1991-1994 as part of a randomized clinical protocol.


RESULTS
Positive TIMP-1 immunoreactivity was found in 12.3% of the tumours. The median survival time for the 143 patients with TIMP-1 negative tumours was 23.7 months [19.0-29.4] 95% CI, while the median survival time for the 20 patients with TIMP-1 positive tumours was 15.9 months [12.3-27.4] 95% CI. Although a difference of 7.8 months in median overall survival in favor of the TIMP-1 tumour negative patients was found, this difference did not reach statistical significance (p = 0.28, Kaplan-Meier, log-rank test). Moreover, TIMP-1 immunoreactivity was not associated with CA125 response (p = 0.53) or response at second look surgery (p = 0.72).


CONCLUSIONS
TIMP-1 immunoreactivity in tumour tissue from patients with primary epithelial ovarian cancer did not correlate with patient survival or response to combination platinum/cyclophosphamide therapy.
Steffensen
Karina Dahl
KD
Department of Oncology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark. Karina.Dahl.Steffensen@slb.regionsyddanmark.dk
Waldstrøm
Marianne
M
Christensen
Rikke Kølby
RK
Bartels
Annette
A
Brünner
Nils
N
Jakobsen
Anders
A
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018394:CA-125 Antigen / Q000097:blood; D016190:Carboplatin / Q000008:administration & dosage; D002277:Carcinoma / Q000737:chemistry* / Q000401:mortality / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D013509:Gynecologic Surgical Procedures; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D024162:Second-Look Surgery; D013997:Time Factors; D046888:Tissue Array Analysis / Q000379:methods*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis*; D016896:Treatment Outcome
D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D003520:Cyclophosphamide; D016190:Carboplatin
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