Altered urinary profiles of endogenous steroids in postmenopausal women with adenocarcinoma endometrii.

OBJECTIVE: The potential role of androgen metabolism as co-factors in the development of carcinoma endometrii was investigated. DESIGN: The urinary concentration of 23 androgen, progesterone and corticoid metabolites was quantitatively determined by gas chromatography-mass spectrometry with selected ion-monitoring. We obtained 24-h urine samples from 13 patients with adenocarcinoma endometrii and from 10 age-matched normal female subjects. In the course of the urinary steroid determination, we observed changes in the steroid profiles in the disease examined compared to the same age and same sex control group. Profiling urinary steroids has to give comprehensive information about the synthesis of steroids including the glandular and peripheral steroid metabolisms. RESULTS: The concentrations of 16-hydroxy- dehydroepiandrosterone, pregnanediol and pregnenediol were not significantly different in the two groups. The concentrations of androsterone, etiocholanolone, 11beta-hydroxy-androsterone, 11beta-hydroxy-etiocholanolone, pregnanetriol, pregnenetriol, tetrahydrocortisone, tetrahydro-11-dehydrocorticosterone, tetrahydro-corticosterone, allo-tetrahydro-corticosterone, tetrahydrocortisol, allo-tetrahydrocortisol, alpha-cortolone, beta-cortolone and alpha-cortol were significantly lower in the postmenopausal women with adenocarcinoma than in the controls. CONCLUSION: The changes in the concentrations of single metabolites point out the important role of steroid group, thus providing help in the recognition and treatment of diseased states.

Differential Urinary Proteomic Analysis of Endometrial Cancer.

Endometrial cancer is one of the most frequent gynecological malignancies present in more than 95 % of all uterine cancers. In spite of that, screening of such disease is not commonly performed in clinical practice due to enormous costs and relatively low sensitivity. Therefore, developing an effective screening test to diagnose endometrial cancer at early stages is of great importance for the clinical area of investigation. In this work, we applied urinary proteomics (i.e., bottom-up proteomic approach followed by nano HPLC-ESI-MS/MS) in patients with endometrial cancer, with respect to find proteins aimed for the early diagnostics and screening. According to the results, the significant semi-quantitative changes were observed in urinary proteome of treated patients. The proteins that may be pivotal in pathogenesis of endometrial cancer, like cadherin-1 (CDH1), vitronectin (VTN) and basement membrane specific-heparan sulphate proteoglycan core protein (HSPG2) were down-regulated, when compared to the control group. Ultimately, it can be stated that urinary proteomics has a potential for the searching of cancer protein biomarkers based on their altered concentration.

Proteomic-based discovery and characterization of glycosylated eosinophil-derived neurotoxin and COOH-terminal osteopontin fragments for ovarian cancer in urine.

PURPOSE: The objective was to identify and characterize low molecular weight proteins/peptides in urine and their posttranslational modifications that might be used as a screening tool for ovarian cancer. EXPERIMENTAL DESIGN: Urine samples collected preoperatively from postmenopausal women with ovarian cancer and benign conditions and from nonsurgical controls were analyzed by surface-enhanced laser desorption/ionization mass spectrometry and two-dimensional gel electrophoresis. Selected proteins from mass profiles were purified by chromatography and followed by liquid chromatography-tandem mass spectrometry sequence analysis. Specific antibodies were generated for further characterization, including immunoprecipitation and glycosylation. Quantitative and semiquantitative ELISAs were developed for preliminary validation in patients of 128 ovarian cancer, 52 benign conditions, 44 other cancers, and 188 healthy controls. RESULTS: A protein (m/z approximately 17,400) with higher peak intensities in cancer patients than in benign conditions and controls was identified and subsequently defined as eosinophil-derived neurotoxin (EDN). A glycosylated form of EDN was specifically elevated in ovarian cancer patients. A cluster of COOH-terminal osteopontin was identified from two-dimensional gels of urine from cancer patients. Modified forms EDN and osteopontin fragments were elevated in early-stage ovarian cancers and a combination of both resulted to 93% specificity and 72% sensitivity. CONCLUSIONS: Specific elevated posttranslationally modified urinary EDN and osteopontin COOH-terminal fragments in ovarian cancer might lead to potential noninvasive screening tests for early diagnosis. Urine with less complexity than serum and relatively high thermodynamic stability of peptides or metabolites is a promising study medium for discovery of the novel biomarkers which may present in many non-urinary tract neoplastic diseases.

Atypical squamous cells in the urine revealing endometrioid adenocarcinoma of the endometrium with squamous cell differentiation: a case report.

Urine cytology is mainly used to detect urothelial carcinoma (UC), especially for high-grade lesions including urothelial carcinoma in situ. Benign squamous cells are often seen in the urine specimens of women, they are either exfoliated from the trigone area of the bladder, the urethra, or the cervicovaginal region. However, abnormal squamous cells in the urine raise concerns of abnormalities of the urinary tract and cervicovaginal area which range from squamous metaplasia of the urothelium, a cervicovaginal squamous intraepithelial lesion, condyloma acuminatum of the bladder, UC with squamous differentiation, and squamous cell carcinoma. We present here a unique case of atypical squamous cells (ASCs) in the urine subsequently leading to the diagnosis of endometrioid adenocarcinoma of the endometrium with squamous differentiation. The presence of ASCs in voided urine is a rare finding that may indicate an underlying malignancy. Careful evaluation of squamous cells in the urine is an important part of our daily cytopathology practice.

Endometrial adenocarcinoma associated with elevated serum concentrations of the free beta subunit of human chorionic gonadotropin.

We report a case of a histologic grade II endometrial adenocarcinoma without trophoblastic differentiation in a 24-year-old woman with an elevated serum concentration of human chorionic gonadotropin (hCG) and with no evidence of pregnancy. Serum and urine specimens were used to study the hCG immunoreactivity. Qualitative tests performed on serum and urine using 5 different assays produced conflicting results. The hCG concentration in serum and urine was quantified using assays designed to detect different molecular forms of the molecule; analysis revealed that serum hCG immunoreactivity was due entirely to the presence of the free beta subunit. Immunohistochemical analysis performed on tissue samples showed strong cytoplasmic staining for hCG. While hCG is a well-recognized tumor marker in gynecologic malignant neoplasms, immunoreactivity most often is due to the presence of both intact molecule and the free beta subunit. To our knowledge, this is the first report of an endometrial adenocarcinoma producing only the free beta subunit of hCG.