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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to evaluate tissue and steroid receptor heterogeneity in endometrial carcinoma specimens as a possible source of discordance between biochemically assayed receptor status and response to endocrine treatment. For this purpose the oestrogen receptor (OR) and progesterone receptor (PR) levels in specimens from 16 endometrial carcinoma patients were analysed on adjacent tissue sections using both a radiochemical and an immunohistochemical assay. With immunohistochemical receptor analysis extensive tissue and tumour cell receptor heterogeneity was observed. Many tumour samples revealed up to 75 per cent contamination with benign tissue. In the majority of cases, evaluation of immunoreactivity in normal tissue elements of the specimen could explain the apparent discordance between semiquantitative immunohistochemical receptor scoring of tumour cells and radiochemical receptor assay. Immunohistochemical analysis of OR and PR in endometrial carcinoma specimens allows a more specific determination of tumour cell receptor content and hence may yield a more accurate prediction of response to endocrine therapy than the biochemical assay.
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PMID:Is immunohistochemical analysis of oestrogen and progesterone receptors in endometrial carcinoma superior to the radioligand binding assay? 219 40

The rationale for endocrine therapy in patients with advanced endometrial carcinoma may be based on the presence of estrogen or progesterone receptors in the primary tumor. A study was designed to evaluate tumor cell heterogeneity of steroid hormone receptors in the primary and metastatic sites in endometrial cancer. Primary endometrial cancer tissue samples from 10 patients and 16 metastatic tumor sites were simultaneously analyzed for estrogen and progesterone receptors, using a radioligand biochemical assay. The primary tumor was estrogen receptor (ER) and progesterone receptor (PR) positive in 70 and 60% of the patients, respectively. The metastatic sites were ER positive in 63% and PR positive in 25%. The primary tumor tissue and the metastatic disease showed an identical ER and PR status in only 25 and 19%, respectively. Four patients had multiple metastatic sites analyzed. In two of four patients the PR values, and in three of four patients the ER values, in these metastatic sites were discordant. These data support the concept of tumor cell heterogeneity for steroid hormone receptors in endometrial cancer. To optimize treatment planning, it may be important to biopsy primary, metastatic, and recurrent tumor sites for individual analysis of receptor activity.
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PMID:Heterogeneity in hormone receptor status in primary and metastatic endometrial cancer. 222 58

Although hormonal agents have been used to treat endometrial cancer for nearly 30 years, response rates have remained essentially unchanged. Furthermore, objective response rates vary considerably from institution to institution, presumably because of differences in accepted response criteria and patient selection. The latter is particularly influenced by the distribution within the treated population of well-differentiated and poorly differentiated tumor histologic types. Nevertheless, the rapid attrition after hormonal therapy begins and the limited long-term salvage in nonselected patients with advanced primary or recurrent disease suggest primary nonresponsiveness or acquired tumor refractoriness to hormonal therapy. The determination of tumor progesterone receptor levels has made it easier to identify patients with sensitivity to such therapy. Recent investigations have shown favourable response rates (72%) after administration of progestational agents in patients with progesterone receptor-rich tumors. Similarly, responses have been reported with antiestrogens and combination progestin-antiestrogen therapy, recent laboratory observations having suggested potential benefit from sequential administration. Although these clinical and laboratory findings are encouraging, the limited duration of objective responses and the poor long-term survival rates continue to temper enthusiasm for routine hormonal therapy. Properly stratified (according to pathologic, biochemical, and clinical criteria), prospective, randomized, double-blind studies with more definitive end points, such as progression-free survival and overall survival, are mandatory to further evaluate the merits of various therapeutic regimens using gonadal hormones.
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PMID:Hormonal therapy in endometrial carcinoma. 223 40

We previously showed that combined treatment with tamoxifen and progestin was effective in arresting the growth of human endometrial carcinomas in the nude mouse model. After a 15- to 20-week tumoristatic period, the tumors began to regrow, reminiscent of the clinical situation. Lack of progestin sensitivity during the regrowth period appeared to reflect the absence of progesterone receptor. To test the prediction that intermittent progestin administration may circumvent the regrowth phenomenon, the effect of various doses of progestin on blood progestin levels, EnCa 101 tumor progesterone receptor profiles, and rate of tumor growth were examined. Whereas 1 mg progestin was ineffective in totally down-regulating tumor progesterone receptor, 2 and 5 mg doses resulted in the total disappearance of tumor progesterone receptor by 1 week followed by its reappearance at 5 to 6 weeks and 9 to 10 weeks, respectively. On the basis of these results we predict that intermittent progestin administration may result in better control of endometrial cancer growth in the nude mouse system.
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PMID:Designing a schedule of progestin administration in the control of endometrial carcinoma growth in the nude mouse model. 232 63

Endometrial carcinoma, now the most frequent female genital tract malignancy in Denmark, is generally accepted as an endocrine-related neoplasm. Like normal endometrium, many endometrial carcinomas contain estrogen receptors as well as progesterone receptors. The receptor content appears to correlate with several histopathological features, in particular with tumour differentiation. Well-differentiated lesions are more frequently estrogen and progesterone receptor "positive" than poorly differentiated lesions. Several studies suggest that a high content of estrogen/progesterone receptors in primary endometrial carcinomas, regardless of other prognostic factors, affects the prognosis favourably. Furthermore, receptor status seems to correlate with response of the tumour to progestin therapy. It may be of particular importance, that nearly half of poorly differentiated endometrial carcinomas contain estrogen/progesterone receptors and thus might benefit from progestin therapy. Immunohistochemical receptor analysis directly on cryostat or formalin-fixed tissue sections increases the possibility to explore the histological and biological features, which are determinative for the receptor profile of endometrial carcinomas.
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PMID:[Endometrial cancer and steroid hormone receptors]. 240 23

Tissue samples of three endometrial carcinomas, seven ovarian carcinomas, and 24 mammary carcinomas were analyzed for estrogen receptor (ER) by enzyme immunoassay (EIA) and a conventional dextran-coated charcoal (DCC) method. In addition, ER and progesterone receptor were assayed by DCC only in 68 ovarian carcinoma specimens. All three endometrial cancer specimens showed elevated ER values by both assays. As with mammary cancers the ER-EIA values tend to be higher than DCC values. It was intriguing to note that negative Scatchard plot data resulted in residual ER levels in the EIA system. Also four ovarian cancer specimens with negative ER values by the DCC assay had detectable levels by ER-EIA, and three of these four had ER-EIA values less than or equal to 10 fmol/mg of protein. Of the ten breast cancers with negative DCC values, seven were less than or equal to 10 fmol/mg of protein by the ER-EIA. Good correlation (r = 0.88) between EIA and Scatchard plot data was calculated from ER data of 24 mammary carcinoma tissue samples. Receptor assays in 68 ovarian cancer patients indicate that ER determinations should become a useful tool in the management of patients bearing this carcinoma. In addition, receptor determinations may improve the possibility of predicting which well differentiated Stage I ovarian carcinomas are likely to recur. Present data combine to suggest that ER-EIA may become a useful diagnostic laboratory tool.
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PMID:Enzyme immunoassay and Scatchard plot estimation of estrogen receptor in gynecological tumors. 242 49

The crossreactivity of monoclonal antibodies (hPRa 1, 2, 3 and 6) generated against human progesterone receptor was examined in six mammalian and an avian species using the techniques of sodium-dodecylsulfate polyacrylamide gel electrophoresis and Western blot analysis. Immunoreactive bands were detected on protein blots of receptor-containing preparations from human endometrial carcinoma grown in nude mice, human T47D breast cancer cells, rabbit, cow and mouse uteri, and chick oviduct. No receptor-associated, immunoreactive bands were detected in rat, guinea pig or hamster uteri. The number and molecular weights of the receptor subunits detected varied between species, and only human progesterone receptor displayed electrophoretic microheterogeneity in its high molecular weight subunit. These data demonstrate that the human progesterone receptor antibodies recognize epitopes not common to all species.
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PMID:Species crossreactivity of human progesterone receptor monoclonal antibodies: Western blot analysis. 246 66

Forty-two cases of recurrent and 14 cases of advanced clinical stage (III and IV) endometrial carcinoma are presented, in which progesterone and estrogen receptors from the metastatic sites were measured. Mean survival time (time from recurrence or, in advanced stages, from the time of diagnosis to death or last follow-up), mean total survival time (time from diagnosis to death or last follow-up), and mean time to recurrence (time from diagnosis of primary tumor to the time of recurrence) were positively correlated with positive progesterone and estrogen receptor status and with histologic grade of tumor. No correlation was found with age, clinical stage, depth of myometrial invasion, or site of metastasis. However, when multiple variables were considered with the Cox regression model, the combination most highly correlated with survival included progesterone receptor, grade of tumor, and site of metastasis (pelvis vs. other sites). All differences were statistically significant (p less than 0.05). We conclude that measurement of progesterone and estrogen receptors in metastatic or recurrent endometrial tumors may be used as an additional prognostic variable.
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PMID:Prognostic significance of steroid receptors measured in primary metastatic and recurrent endometrial carcinoma. 258 47

TAG-72 is a tumor-associated antigen that is expressed by secretory endometrium and most endometrial adenocarcinomas. We used immunohistochemical techniques to quantitate expression of TAG-72, estrogen receptor, and progesterone receptor in 21 normal endometria and 44 endometrial adenocarcinomas. In normal cycling endometrial glands, TAG-72 expression was related inversely to expression of receptors for estrogen and progesterone. This suggests that TAG-72 expression in normal endometrium may be hormonally regulated. Ninety-one percent of endometrial adenocarcinomas expressed immunohistochemically detectable TAG-72. The magnitude of TAG-72 expression did not correlate with other known prognostic factors in endometrial cancer such as histologic grade, depth of myometrial invasion, surgical stage, or steroid receptor status. The production of TAG-72 by most endometrial adenocarcinomas may represent nonspecific expression by cells that have dedifferentiated.
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PMID:Immunohistochemical expression of TAG-72 in normal and malignant endometrium: correlation of antigen expression with estrogen receptor and progesterone receptor levels. 258 48

The precursor of cathepsin D, a lysosomal acidic protease, is secreted by human breast cancer cells, where its synthesis is specifically induced by estrogens and growth factors. In this study, we investigated the hormonal regulation of cathepsin D and its mRNA in uterine cells. In the Ishikawa endometrial cancer cell line, epidermal growth factor (EGF) increased the level of cathepsin D and its mRNA 2- to 3-fold. Although expression of the transiently transfected estrogen-responsive recombinant (Vit. tk. CAT) and the endogenous progesterone receptor was markedly increased by estradiol in Ishikawa cells, estradiol did not alter the level of cathepsin D or its mRNA. The progestin R5020 induced the expression of the LTR sp65 CAT, which contains the progesterone-responsive element of the MMTV but it too was without effect on cathepsin D. By contrast, the expression of cathepsin D gene, in normal rat uterus, was increased by R5020 but not by estradiol. We conclude that cathepsin D gene expression is regulated differently by sex steroid hormones in endometrial and breast cancer cell lines, whereas it is similarly induced by EGF in these cells.
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PMID:Differential regulation of cathepsin D by sex steroids in mammary cancer and uterine cells. 261 33


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