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Urokinase-like plasminogen activator (ULPA) was determined with a radioimmunoassay in uterine aspirates from 67 patients prior to curettage. In women with normal endometrial histology the mean concentration of ULPA was 5.4 t 2.5 pg per liter. Only one of this aspirates contained more than 8 pg per liter. In cases with malignant histology ULPA was above this level in 10 of 11 with a mean concentration of 31.2 t 31.4 pg per liter. In cases with glandular cystic hyperplasia andor adenomatous hyperplasia 6 of 15 had values above 8 pg per liter with a mean of 10.3 & 6.1 pg per liter. In addition to other parameters of malignancy such as cytology, detection of ULPA in uterine fluid might prove useful in screening examinations for endometrial neoplasia.Cancer 48:1484-1486, 1981.EOPLASTIC CELLS I N culture release fibrinolytic N enzyme^^,^*'^ which have been shown to be activators of plasminogen.2,10,21 It has also been shown that abundant amounts of plasminogen activators are released in cultures of transformed cells in contrast to minor amounts found in cultures of their untransformed c~u n t e r p a r t s .~,~~, '~ In cultured human ovarian carcinoma, a stable plasminogen activator is released that has been shown to cross-react with the plasminogen activator present in urine, ~r o k i n a s e .~~ Recently such cross-reaction has also been shown for plasminogen activators released from several other types of malignant cell^.'^,^^ A radioimmunoassay (RIA) has been designed to determine urokinase levels and has been applied for the detection of neoplastic antiurokinasereacting plasminogen activator.We report here the detection of antiurokinasereacting material in endouterine aspirates to evaluate its potential as a biologic marker for endometrial neoplasia. Material and MethodsThe clinical material consisted of 67 patients with bleeding disorders subjected to diagnostic curettage. Before curettage was performed, uterine fluid had Accepted for publication July 30, 1980. been obtained using a new technique for endouterine aspiration.12 According to the histologic diagnosis of material obtained at curettage or other surgical procedure, the patients were divided into three groups having:1. Normal histology 2. Atypical histology a. Polyps and/or other atypia b. Glandular cystic hyperplasia and adenomatous h yperplasia 3. Malignant histologyThe uterine fluid prior to the curettage was analyzed for the presence of antiurokinase-reacting material.For RIA of antiurokinase-reacting material an antiserum against human urokinase was raised in rabbits.fi Iodine-125-urokinase was prepared with the lactoperoxidase methodlg and the RIA was performed with a double antibody s y~t e m . '~ The sensitivity is 2-4 pg/liter, but because of an nonspecific protein interaction in the assay, values less than 8 pg/liter were considered below the limit of detection. ResultsOf the entire material of 67 patients (FIG. 1) normal histology (Group 1) was found in 33 of which nine patients were in a proliferative phase, seven in a secretory phase and...
Urokinase-like plasminogen activator (ULPA) was determined with a radioimmunoassay in uterine aspirates from 67 patients prior to curettage. In women with normal endometrial histology the mean concentration of ULPA was 5.4 t 2.5 pg per liter. Only one of this aspirates contained more than 8 pg per liter. In cases with malignant histology ULPA was above this level in 10 of 11 with a mean concentration of 31.2 t 31.4 pg per liter. In cases with glandular cystic hyperplasia andor adenomatous hyperplasia 6 of 15 had values above 8 pg per liter with a mean of 10.3 & 6.1 pg per liter. In addition to other parameters of malignancy such as cytology, detection of ULPA in uterine fluid might prove useful in screening examinations for endometrial neoplasia.Cancer 48:1484-1486, 1981.EOPLASTIC CELLS I N culture release fibrinolytic N enzyme^^,^*'^ which have been shown to be activators of plasminogen.2,10,21 It has also been shown that abundant amounts of plasminogen activators are released in cultures of transformed cells in contrast to minor amounts found in cultures of their untransformed c~u n t e r p a r t s .~,~~, '~ In cultured human ovarian carcinoma, a stable plasminogen activator is released that has been shown to cross-react with the plasminogen activator present in urine, ~r o k i n a s e .~~ Recently such cross-reaction has also been shown for plasminogen activators released from several other types of malignant cell^.'^,^^ A radioimmunoassay (RIA) has been designed to determine urokinase levels and has been applied for the detection of neoplastic antiurokinasereacting plasminogen activator.We report here the detection of antiurokinasereacting material in endouterine aspirates to evaluate its potential as a biologic marker for endometrial neoplasia. Material and MethodsThe clinical material consisted of 67 patients with bleeding disorders subjected to diagnostic curettage. Before curettage was performed, uterine fluid had Accepted for publication July 30, 1980. been obtained using a new technique for endouterine aspiration.12 According to the histologic diagnosis of material obtained at curettage or other surgical procedure, the patients were divided into three groups having:1. Normal histology 2. Atypical histology a. Polyps and/or other atypia b. Glandular cystic hyperplasia and adenomatous h yperplasia 3. Malignant histologyThe uterine fluid prior to the curettage was analyzed for the presence of antiurokinase-reacting material.For RIA of antiurokinase-reacting material an antiserum against human urokinase was raised in rabbits.fi Iodine-125-urokinase was prepared with the lactoperoxidase methodlg and the RIA was performed with a double antibody s y~t e m . '~ The sensitivity is 2-4 pg/liter, but because of an nonspecific protein interaction in the assay, values less than 8 pg/liter were considered below the limit of detection. ResultsOf the entire material of 67 patients (FIG. 1) normal histology (Group 1) was found in 33 of which nine patients were in a proliferative phase, seven in a secretory phase and...
The distribution of carcinoembryonic antigen (CEA), secretory component (SC), fat globule membrane antigens (FGMA), and keratin was determined immunohistochemically in 22 invasive adenocarcinomas of various types and in 9 adenocarcinomas in situ of the uterine cervix. In the invasive adenocarcinomas 77% were positive for CEA, 47% for SC, 89% for keratin, and 77% for FGMA. In adenocarcinomas in situ 67% were positive for CEA, 11% for SC, and 44% for keratin. The location of the markers was variable in the cells, and the cells in a tumor were irregularly positive. For a given histologic type there were several phenotypes. No correlation was found between histologic types of invasive adenocarcinomas and the various phenotypes. It remains to be shown whether a particular phenotype has a particular biological behavior. The detection in the serum of the markers shown in histologic preparations could be useful in the postsurgical monitoring.
Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States, accounting for some 36,000 cases of invasive cancer each year. Hyperplastic lesions of the endometrium follow a continuum, with the risk of progression to carcinoma being related to the severity of the disorder. Risk factors associated with the development of adenocarcinoma include hyperplasia, obesity, menstrual abnormalities, diabetes, hypertension, prior pelvic irradiation, sequential oral contraceptive use, diet, and exogenous estrogen use. There is also some evidence of genetic predisposition, and some data indicating the possibility of specific genetic abnormalities and activation of oncogenes as factors determining the etiology of the disease. At this time there is no accepted screening test for endometrial carcinoma, though the role of immunochemistry techniques for screening and follow-up has just begun to be realized. Dilatation and curettage along with hysteroscopy remain the major means of diagnosis. A variety of prognostic variables including tumor cell type, histologic grade, depth of myometrial invasion, status of peritoneal cytology, presence of disease in preformed vascular spaces, presence of adnexal metastases, and presence of cervical involvement have been defined. Although the treatment plan for each patient must be individualized, the mainstay of treatment remains total abdominal hysterectomy with bilateral salpingo-oophorectomy. Metastatic and recurrent disease is usually treated with hormonal therapy and systemic chemotherapy. Radiation therapy like surgery in recurrent disease is only applicable for the treatment of local recurrences.
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