Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum levels of TAG 72 were measured in 726 serum samples from patients with benign and malignant gynaecological conditions in order to evaluate the clinical usefulness of TAG 72 alone or in combination with other tumour markers. Sixty-six per cent of patients with ovarian cancer showed abnormal concentrations of TAG 72 antigen. A good correlation was also found between serial TAG 72 values and the clinical course of disease during chemotherapy and follow-up. In cervical and endometrial cancer abnormal TAG 72 values occurred in 23% and 14% of cases, while none of the patients with breast cancer had abnormal TAG 72 levels. Among patients with benign disease only one out of 12 patients (8%) with benign ovarian tumours and one of 15 patients with uterine fibromyomatosis (7%) showed high TAG 72 serum levels. However, the determination of TAG 72 did not increase the sensitivity of CA 125 and squamous cell carcinoma antigen (SCC), in ovarian and cervical cancer, respectively. The systemic administration of recombinant interferon alpha-2b to 15 patients with ovarian cancer and different basal levels of TAG 72 did not increase serum levels of the antigen.
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PMID:Serum levels of tumour associated glycoprotein (TAG 72) in patients with gynaecological malignancies. 216 24

We evaluated 109 women with endometrial carcinoma to determine the accuracy of preoperative tumor-associated antigen levels (CA 125, CA 72, CA 15-3) for prediction of extrauterine disease and whether TAG 72, CA 15-3, or both would improve the predictive value of CA 125 alone. Eleven (12%) of 80 patients with disease confined to the uterus or positive cytologic findings had CA 125 values greater than 35 U/ml versus 12 (65%) of 20 patients with extrauterine metastasis. Therefore CA 125 values had sensitivity of 65% and specificity of 88%. The TAG 72 level was elevated (greater than 6 U/ml) in 4% of patients with localized disease and 30% with metastasis. CA 15-3 was elevated (greater than 30 U/ml) in 17% and 65% in these categories, respectively. TAG 72 or CA 15-3 levels did not improve the combination of sensitivity and specificity of CA 125 alone. In addition, only one of 10 patients with microscopic metastasis (three cases) or positive peritoneal cytology (seven) had elevation of any of these tumor-associated antigen levels. Failure to detect occult metastasis and a high false-positive rate limit the role of these tumor-associated antigen assays in the preoperative evaluation of patients with endometrial carcinoma.
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PMID:Preoperative evaluation of serum CA 125, TAG 72, and CA 15-3 in patients with endometrial carcinoma. 222 Sep 31

Monoclonal antibody (MAb) B72.3 binds a high molecular weight tumor-associated glycoprotein designated TAG-72. This study reports the isolation and characterization of secreted TAG-72 directly from effusions of ovarian, colorectal, pancreatic, and endometrial carcinoma patients and compares them to TAG-72 derived from the LS-174T colon carcinoma xenograft. The B72.3-reactive antigen, TAG-72, was used as immunogen to produce second generation anti-TAG-72 MAbs. One of these second generation MAbs, CC49, had a higher affinity than that of B72.3 and was utilized as an affinity reagent in a procedure to purify the TAG-72 present in the serous effusions of carcinoma patients. A three-step purification procedure, utilizing heat extraction, CC49 antibody affinity chromatography, and gel filtration chromatography, resulted in 1000- to 4400-fold purifications of the TAG-72 derived from effusions, as analyzed using a double-determinant radioimmunoassay. Radiolabeled TAG-72 from each of the effusions demonstrated similar high molecular weight bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Similar results from the various effusions were also obtained in Western blotting analyses. Analyses of TAG-72 from the different effusions in radioimmunoassay using five different anti-TAG-72 MAbs revealed similar binding patterns. The results of these studies thus indicate that TAG-72 obtained directly from patients with ovarian, colorectal, endometrial, and pancreatic carcinomas and the LS-174T xenograft are highly similar in terms of immunochemical properties and antigenic profile.
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PMID:Characterization of the shed form of the human tumor-associated glycoprotein (TAG-72) from serous effusions of patients with different types of carcinomas. 237 52

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

Forty patients, originally diagnosed as endometrial hyperplasia, were reviewed histopathologically and evaluated for immunohistochemical staining with antibodies directed against TAG-72 and MSN-1 antigens. All patients had follow-up endometrial biospies or hysterectomies from 1 to 13 years later. The extent of regression to normal of nonhyperplastic endometrium, persistence as any type of endometrial hyperplasia, or progression to endometrial adenocarcinoma was correlated with the histologic hyperplastic subtype and immunohistochemical staining. As expected, cases of complex or atypical hyperplasia more often progressed to carcinoma than cases of simple or no hyperplasia. Interestingly, MSN-1 positivity was more prevalent in cases of higher grades than lower grades of hyperplasia and was associated with the tendency to show persistent hyperplasia or progression to carcinoma. B72.3 positivity was uncommon in the hyperplastic endometrium and was not correlated with clinical regression or progression. Although the tendency for progression of endometrial hyperplasia to endometrial carcinoma is best judged histologically, MSN-1 may add prognostic information in subgroups of hyperplasia.
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PMID:Use of monoclonal antibodies MSN-1 and B72.3 in the prediction of the natural history of endometrial hyperplasia. 834 62

In this report we describe a cDNA sequence, BS106, identified from Incyte Genomics LifeSeq Expressed Sequence Tag database. A multi-tissue mRNA expression array, northern blots, and RT-PCR assays demonstrate the expression of BS106 in mammary, salivary and prostate glands, but not in other tissue types. BS106 mRNA was detected in 90% of the breast tissues examined. The cDNA encodes a 90-amino acid protein characterized as a small, mucin-like protein based on amino acid composition, extensive O-linked glycosylation, and expression profile. BS106 protein was recombinantly expressed in human embryonic kidney 293 cells and the secreted product was purified from the culture media. Monoclonal antibodies were prepared and used for immunohistochemical analysis of early stage breast cancer. BS106 protein was detected in the vast majority of carcinomas (70-100%) and overexpressed in approximately 30% of the 22 specimens analyzed. BS106 protein was not detected in other solid tumor types including bladder carcinoma, colon carcinoma, endometrial carcinoma, gastric carcinoma, squamous cell lung carcinoma, adenocarcinoma of the lung, ovarian carcinoma, pancreatic and prostatic carcinoma.
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PMID:Identification and immunohistochemical characterization of a mucin-like glycoprotein expressed in early stage breast carcinoma. 1259 43

CA 125 is the most reliable serum marker for ovarian carcinoma. Whereas its role in the screening of the malignancy is controversial, serum CA 125 assay is very useful for both the differential diagnosis of ovarian masses, particularly in postmenopause, and the monitoring of the response to chemotherapy and follow-up of patients with histologically proven ovarian carcinoma. Tumor-associated antigens other than CA 125, such as CA 19.9, CA 15.3 and TAG.72, firstly identified in gastro-intestinal or breast malignancies, have been detected also in tissue and serum samples from patients with ovarian carcinoma. In particular CA19.9 offers the advantage of high sensitivity for mucinous histotype, which often fails to express CA 125. Serum CA 125 correlates with the clinical course of disease better than the other antigens, and in patients with positive CA 125 assay at diagnosis the concomitant evaluation of CA 19.9 or CA 72.4 or CA 15.3 does not offer any additional benefit for monitoring ovarian carcinoma. Conversely, the serial measurements of these other antigens may represent an interesting biochemical tool for the management of patients with negative CA 125 assay. Serum alphaFP and betaHCG are very useful in the preoperative evaluation and management of nondysgerminomatous ovarian germ cell tumors, whereas elevated serum inhibin levels can be detected in patients with granulosa cell tumors of the ovary. As for endometrial carcinoma, preoperative serum CA 125 levels correlate with stage, depth of myometrial invasion, histologic grade, cervical invasion, peritoneal cytology, lymph node status and clinical outcome. Moreover, serial CA 125 assay is a good indicator of disease activity and a useful biochemical tool for post-treatment surveillance of patients with endometrial carcinoma. SCC is the most reliable serum marker for squamous cell cervical carcinoma, and in patients with this malignancy pretreatment SCC levels are related to tumor stage, tumor size, depth of cervical invasion, lymph-vascular space involvement, lymph node status and clinical outcome. Serial SCC measurements parallel the response to radiotherapy and chemotherapy as well as the clinical course of disease after the completion of treatment. Serum CYFRA 21.1 seems to be less sensitive than serum SCC for squamous cell cervical carcinoma. Elevated CA 125 levels can be often detected in patients with cervical adenocarcinoma. The future for tumor marker research is represented by the emerging technologies of transcriptional profiling and proteomics.
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PMID:Serum tumor markers in the management of ovarian, endometrial and cervical cancer. 1473 59

Excessive exposure to estradiol represents the main risk factor for endometrial cancer. The abnormally high estradiol levels in the endometrium of women with endometrial cancer are most likely due to overproduction by the tumour itself. Endometrial cancer cells express the genes encoding the steroidogenic enzymes involved in estradiol synthesis. Here we used RT-PCR and Western blot to show that the nuclear receptors SF1 and LRH1, two well-known regulators of steroidogenic gene expression in gonadal and adrenal cells, are also expressed in endometrial cancer cell lines. By transient transfections, we found that SF1 and LRH1, but not the related nuclear receptor NUR77, can activate the promoters of three human steroidogenic genes: STAR, HSD3B2, and CYP19A1 PII. Similarly, forskolin but not PMA, could activate all three promoters. In addition, we found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters. All together, our data provide novel insights into the mechanisms of steroidogenic gene expression in endometrial cancer cells and thus in the regulation of estradiol biosynthesis by tumour cells.
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PMID:The nuclear receptors SF1 and LRH1 are expressed in endometrial cancer cells and regulate steroidogenic gene transcription by cooperating with AP-1 factors. 1902 61

Most ovarian cancers arise from the mesothelial surface lining of the ovaries or from invaginations of this lining into the superficial ovarian cortex that form cortical inclusion cysts. Thus, these cysts are thought to be precursor lesions of ovarian carcinoma. Epithelial-mesenchymal transition, which is a transcriptional program for inducing maintenance of the mesenchymal phenotype, acts in tumor progression and metastasis. Little is known about the mechanisms involved in mesenchymal-epithelial transition (MET). We aimed to characterize the human ovarian surface epithelium (OSE) and inclusion cysts by immunohistochemical analysis to examine whether MET occurs during inclusion cyst formation in the OSE. We used specimens from 9 endometrial cancer patients who had undergone hysterectomy and bilateral salpingo-oophorectomy. Immunohistochemical analysis was performed in 10 normal ovaries containing 92 inclusion cysts and in 4 normal tubes to examine the expression of antigen markers including calretinin, podoplanin, D2-40, thrombomodulin, HBME-1, vimentin, EMA, WT1, CA125, MOC31, TAG-72, Ber-EP4 and E-cadherin. The positive staining rates for mesothelial markers in normal OSE were 100% (10/10) for calretinin, 80% (8/10) for podoplanin, 80% (8/10) for D2-40, 70% (7/10) for thrombomodulin, 100% (10/10) for HBME-1, 100% (10/10) for vimentin. The positive staining rates for epithelial markers in tubal epithelium were 100% (4/4) for HBME-1, 100% (4/4) for vimentin, 100% (4/4) for EMA, 75% (3/4) for TAG-72, 100% (4/4) for Ber-EP4. Inclusion cysts showed positive staining for both markers with an incidence of 51% (47/92) for HBME-1, 44% (41/92) for vimentin, 65% (60/92) for TAG-72, 88% (81/92) for Ber-EP4. The OSE showed the characteristics of both mesenchymal and epithelium cells. In contrast, inclusion cysts gained epithelial characteristics, but lost mesenchymal characteristics. These findings support that MET occurs during the inclusion cyst formation from OSE.
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PMID:Mesenchymal to epithelial transition in the human ovarian surface epithelium focusing on inclusion cysts. 1936 Feb 96

Endometrial adenocarcinoma is on the basis of the molecular, immunohistological and clinicopathologic features broadly divided into two groups, referred as type I and type II. Type I appears more frequently and in principle patients have a good prognosis; however a significant number of patients develop local recurrences. We hypothesize that TAG-72, expressed on endometrial carcinoma binds and internalizes endocytic pattern recognition receptors on surrounding tissue antigen presenting cells (dendritic cells and macrophages), powers their anti-inflammatory maturation program and make them capable to elicit or modulated tolerogenic immune response mediated by local T and NK effectors. This could support uncontrolled local tumor growth, deeper tumor invasion into surrounding tissues, frequent local recurrences and/or lymph node metastasis. To test this hypothesis, we propose a semi-quantitative immunohistochemical analysis of TAG-72 expression in endometrial adenocarcinoma samples and to correlate the results with clinical and pathological parameters (age, type and histological grade of the tumor, estrogen and progesterone receptor expression, invasion into the myometrium and capillaries, presence of lymph node metastases, FIGO stage, and TNM classification). It would be worthwhile to investigate the local tissue immune response in the tumor environment using tissue samples removed during surgery. These studies could elucidate the underlying immunopathological mechanisms that govern the early recurrence and possibly distant metastases of TAG-72-expressing adenocarcinomas and might help in deciding the type of treatment to be applied in a selected group of cancer patients including application of biological therapy with anti-TAG-72 antibodies, according the principle of personalized oncology treatments.
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PMID:Role of tumor-associated glycoprotein-72 in the progression of endometrial adenocarcinoma: a proposed study. 2576 4


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