Detection of endometrial cancer by determination of matrix metalloproteinases in the uterine cavity.
OBJECTIVE
The known overexpression of matrix metalloproteinases (MMPs) by various tumors prompted a study to determine whether endometrial cancer could be detected by measuring MMPs in uterine cavity washings.


METHODS
The study populations comprised 95 women being treated for endometrial cancer and 98 women with other gynecological conditions. A simple method was developed for performing uterine lavage and preparing cell-free uterine supernatants for MMP analysis. Gelatin zymography revealed elevated levels of latent and active forms of MMP-2 and MMP-9 in patients with endometrial cancer. For each patient individual bands of gelatinase activity were scored from 0 to 5 and summed to provide a total MMP score for analysis.


RESULTS
The mean MMP score in uterine washings of patients with endometrial cancer was 10.0 (range 1 to 22) compared with 0.8 (range 0 to 15) in the group without this cancer (P < 0.001). Receiver operating characteristic analysis showed that an MMP cutoff score of 3 gave a sensitivity of 98% and specificity of 91% for detecting endometrial cancer. With this MMP cutoff, a positive result was 11 times as likely in endometrial cancer compared to other conditions. The mean MMP score in the group with nodal metastases (14.1) was significantly higher than that without nodal involvement (9.4, P = 0.005). MMP-9 but not MMP-2 was significantly associated with nodal metastasis (P = 0.01). There was no significant association between MMP score and histological grade of tumor, vascular invasion, or depth of myometrial invasion.


CONCLUSIONS
Gelatinase measurement in uterine washings was reliable for confirming the presence of endometrial cancer in the population studied.
Lopata
Alex
A
Department of Obstetrics and Gynecology, University of Melbourne, Victoria 3052, Australia. alexader@unimelb.edu.au
Agresta
Franca
F
Quinn
Michael A
MA
Smith
Catherine
C
Ostor
Andrew G
AG
Salamonsen
Lois A
LA
D000328:Adult; D018269:Carcinoma, Endometrioid / Q000201:enzymology* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008875:Middle Aged; D007507:Therapeutic Irrigation
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9