Elsevier

Gynecologic Oncology

Volume 90, Issue 2, August 2003, Pages 318-324
Gynecologic Oncology

Regular article
Detection of endometrial cancer by determination of matrix metalloproteinases in the uterine cavity

https://doi.org/10.1016/S0090-8258(03)00328-7Get rights and content

Abstract

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.

Conclusion

Gelatinase measurement in uterine washings was reliable for confirming the presence of endometrial cancer in the population studied.

Introduction

Endometrial cancer is the most common malignancy of the female reproductive tract with an estimated 38,300 new cases being diagnosed in the United States in 2001 [1]. In comparison, it has been estimated that 12,900 new cases of cervical cancer and 23,400 new cases of ovarian cancer were detected during the same year. This high incidence of cancer of the uterine corpus makes it the fourth most common cancer in females. It has also been estimated that endometrial cancer comprises 6% of all malignancies in women in the United States, 5% for Canada [2], and 4% for Australia [3]. Despite this relatively high incidence of uterine cancer, particularly in postmenopausal women, a suitable screening test is currently not available [1]. Yet it is known that a favorable feature of the disease is the high survival rate provided the cancer is detected and treated when it is still confined to the body of the uterus [4], [5]. Such information strongly suggests that it would be important to have a simple and effective test for detecting all stages of endometrial cancer, providing the test was accurate, inexpensive, widely applicable, and acceptable to both patients and physicians [6].

Currently available diagnostic tests for uterine cancer depend on measurements of endometrial thickness by ultrasonography, histological evaluation of endometrial samples, or the inspection of the endometrial surface by hysteroscopy. Such techniques require both expensive equipment and highly trained specialists. Studies that have evaluated such procedures for screening postmenopausal women have generally concluded that these techniques are not cost-effective in terms of the number of cancers detected or the potential outcome of the disease in the surveyed population [7], [8], [9].

Recently, evidence has implicated matrix metalloproteinases (MMPs) in tumor invasion and metastasis [10], [11], [12]. Their overexpression occurs in many tumors or their surrounding stroma, including uterine [13], [14], ovarian [15], colorectal [16], and squamous carcinomas of the uterine cervix [17]. We describe here the close association between MMPs, detected in uterine washings, and the presence of endometrial cancer.

Section snippets

Patients

The studies were performed between February 1996 and March 2000 on two groups of women at the Royal Women's Hospital, Melbourne, Australia. One group comprised women with proven uterine cancer who were admitted for hysterectomy while the other group comprised women without uterine cancer, admitted for diagnostic or therapeutic procedures for various gynecological conditions, during the same time period as the cases with endometrial cancer. Subjects in both groups were included in the study

Spectrum of patients

There were 95 patients with endometrial cancer and 98 patients with other gynecological conditions. The mean age of patients with endometrial cancer was 63 years (SD = 11), significantly higher (P < 0.001, unequal variances assumed) than the mean of 44 years (SD = 14) in those with other conditions.

As the difference in mean age between the two groups was large, the influence of age on MMP scores was examined. Although Fig. 1A suggests that there may be a small upward trend in the MMP score in

Discussion

The study showed that gelatinase levels were significantly higher in uterine lavage samples of patients with endometrial cancer compared with a cohort of patients who had other gynecological conditions or no detectable pathology. The gelatinase levels were evaluated semi-quantitatively by scoring the combined intensity of all MMP bands (on a scale of 0 to 5 for each band) on zymography. When the cutoff MMP score was set at ≥3, an optimum value obtained from a receiver operating characteristic

Acknowledgements

We are grateful to Dr. Deborah Neesham for helping with the uterine irrigations and to Sr. Julene Hallo for recruiting patients. LAS is supported by the NH&MRC of Australia (Grant 143798). The study was funded by a grant from the Women's & Children's Health Care Network, Melbourne, Australia.

References (20)

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