lewis-x-antigen and Endometriosis

Is endometriosis associated with abnormally located endometrial basalis-like (SSEA1+/SOX9+) cells in the secretory phase functionalis and could they contribute to ectopic endometriotic lesion formation?. Women with endometriosis had an abnormally higher number of basalis-like SSEA1+/SOX9+ epithelial cells present in the stratum functionalis and, since these cells formed 3D structures in vitro with phenotypic similarities to ectopic endometriotic lesions, they may generate ectopic lesions following retrograde menstruation.. Endometrial basalis cells with progenitor potential are postulated to play a role in the pathogenesis of endometriosis and SSEA1 and nuclear SOX9 (nSOX9) mark basalis epithelial cells that also have some adenogenic properties in vitro. Induction of ectopic endometriotic lesions in a baboon model of endometriosis produces characteristic changes in the eutopic endometrium. Retrograde menstruation of endometrial basalis cells is proposed to play a role in the pathogenesis of endometriosis.. This prospective study included endometrial samples from 102 women with and without endometriosis undergoing gynaecological surgery and from six baboons before and after induction of endometriosis, with in vitro assays examining the differentiation potential of human basalis-like cells.. The study was conducted at a University Research Institute. SSEA1 and SOX9 expression levels were examined in human endometrial samples from women aged 18-55 years (by immunohistochemistry (IHC) and qPCR) and from baboons (IHC). The differential gene expression and differentiation potential was assessed in freshly isolated SSEA1+ endometrial epithelial cells from women with and without endometriosis (n = 8/group) in vitro. In silico analysis of selected published microarray datasets identified differential regulation of genes of interest for the mid-secretory phase endometrium of women with endometriosis relative to that of healthy women without endometriosis.. Women with endometriosis demonstrated higher number of basalis-like cells (SSEA1+, nSOX9+) in the functionalis layer of the eutopic endometrium compared with the healthy women without endometriosis in the secretory phase of the cycle (P < 0.05). Induction of endometriosis resulted in a similar increase in basalis-like epithelial cells in the eutopic baboon endometrium. The isolated SSEA1+ epithelial cells from the eutopic endometrium of women with endometriosis had higher expression of OCT4, NANOG, FUT4 mRNA (P = 0.05, P = 0.007, P = 0.018, respectively) and they differentiated into ectopic endometriotic gland-like structures in 3D culture, but not into mesodermal lineages (adipose or bone cells).. N/A.. Small sample size. Bioinformatics analysis and results depends on the quality of published microarray datasets and the stringency of patient selection criteria employed. Differentiation of SSEA-1+ cells was only examined for two mesodermal lineages (adipogenic and osteogenic).. Since endometrial epithelial cells with SSEA1+/nSOX9+ basalis-like phenotype generate endometriotic gland-like structures in vitro, they may potentially be a therapeutic target for endometriosis. An in depth analysis of the function of basalis-like eutopic endometrial epithelial cells might provide insights into their potential deregulation in other disorders of the endometrium including heavy menstrual bleeding and endometrial cancer where their function may be aberrant.. We acknowledge the support by Wellbeing of Women project grant RG1073 (D.K.H., C.E.G.) and R01 HD083273 from the National Institutes of Health (A.T.F.). We also acknowledge the support of Liverpool Women's Hospital Foundation Trust (J.D.), Institute of Translational Medicine (L.D.S., H.A.L., A.J.V., D.K.H.), University of Liverpool, the National Health and Medical Research Council of Australia ID 1042298 (C.E.G.) and the Victorian Government Operational Infrastructure Support Fund. All authors declare no conflict of interest.

Topics: Adult; Animals; Cell Differentiation; Disease Models, Animal; Endometriosis; Endometrium; Epithelial Cells; Female; Humans; Lewis X Antigen; Menstruation Disturbances; Middle Aged; Papio; Prospective Studies; SOX9 Transcription Factor; Young Adult

Can the basal epithelial compartment of the human endometrium be defined by specific markers?. Human endometrial epithelial cells from the basalis express nuclear SOX9 and the cell-surface marker SSEA-1, with some cells expressing nuclear β-catenin. In vitro, primary endometrial epithelial cells enriched for SSEA-1+ show some features expected of the basalis epithelium.. The endometrial glands of the functionalis regenerate from the basalis gland stumps following menstruation. Endometriosis is thought to originate from abnormal dislocation of the basalis endometrium. In the highly regenerative intestinal epithelium, SOX9 and nuclear β-catenin are more highly expressed in the intestinal crypt, the stem/progenitor cell region.. A large prospective observational study analysing full-thickness human endometrial hysterectomy samples from 115 premenopausal women, 15 post-menopausal women and ectopic endometriotic lesions from 20 women with endometriosis.. Full-thickness endometrium from hysterectomy tissues was analysed by immunohistochemistry for SSEA-1, SOX9 and β-catenin. Primary human endometrial epithelial cells from short-term cultures were sorted into SSEA1+/- fractions with a cell sorter or magnetic beads and analysed for markers of differentiation and pluripotency and telomere lengths (TLs) using qPCR, telomerase activity [telomere repeat amplification protocol (TRAP)] and growth in 3D culture.. Similar to the intestinal crypt epithelium, human endometrial basal glandular epithelial cells expressed nuclear SOX9 and contained a rare subpopulation of cells with nuclear β-catenin suggestive of an activated Wnt pathway. The embryonic stem cell-surface marker, SSEA-1, also marked the human endometrial basal glandular epithelial cells, and isolated SSEA-1(+) epithelial cells grown in monolayer showed significantly higher expression of telomerase activity, longer mean TLs, lower expression of genes for steroid receptors and produced a significantly higher number of endometrial gland-like spheroids in 3D culture compared with SSEA-1(-) epithelial cells (P = 0.009). Cells in ectopic endometriosis lesions also expressed SSEA-1 and nuclear SOX9, suggesting that the basalis contributes to ectopic lesion formation in endometriosis following retrograde menstruation.. This is a descriptive study with only short-term culture of the primary human epithelial cells in vitro.. The surface marker SSEA1 enriches for an endometrial epithelial cell subpopulation from the basalis. Since the functional endometrium originates from these cells, it is now possible to study basalis epithelium for stem/progenitor cell activity to extend our current understanding of endometrial biology in health and diseases.. The work included in this manuscript was funded by Wellbeing of Women project grant RG1073 (D.K.H. and C.G.). We also acknowledge the support by National Health and Medical Research Council, RD Wright Career Development Award 465121 and Senior Research Fellowship 1042298, and the Victorian Government's Operation Infrastructure Support Program to C.G. and MRC G0601333 to T.V.Z. All authors have no conflict of interest to declare.. N/A.

Topics: beta Catenin; Cell Differentiation; Cells, Cultured; Endometriosis; Endometrium; Female; Humans; Immunohistochemistry; Lewis X Antigen; Menstruation; Menstruation Disturbances; Phenotype; Prospective Studies; SOX9 Transcription Factor; Telomerase; Telomere Homeostasis

We used a combination assay of serum sialyl SSEA-1 antigen (SLX) and CA125 levels, and evaluated the clinical usefulness of this technique for a differential diagnosis of ovarian cancer, benign ovarian tumor and endometriosis. In 82 patients with ovarian tumors, the sera of 20 (64.5%) of 31 with ovarian cancer and 15 (48.4%) of the 31 with endometriosis (endometrial cyst) were positive for both SLX and CA125, but serum SLX level was 5 U/ml or less in these 14 SLX- and CA125-positive patients with endometriosis. The sera of 16 (80.0%) patients with benign ovarian tumor were negative for both tumor markers. The sera of 3 (9.7%) of 31 with ovarian cancer and the sera of 2 (6.5%) of 31 with endometriosis were negative for both markers. The diagnostic accuracy (true positive rate X true negative rate) of the combination assay for ovarian cancer was 49.0% when the cutoff value of the serum SLX was 38 U/ml but improved to 78.5% when the value was set at 50 U/ml. When the cutoff value of serum SLX was set at 50 U/ml and that of serum CA125 at 35 U/ml, 27 of 37 patients who were positive only for CA125 had endometriosis. From the above observations, a combination assay of serum SLX and CA125 is a promising method for the differential diagnosis of malignant and benign ovarian tumors. Our results also suggest that to improve the diagnostic accuracy, the cutoff value of the serum SLX level should be 50 U/ml for ovarian tumors alone.

Topics: Adenocarcinoma; Adult; Antigens, Tumor-Associated, Carbohydrate; Cystadenoma; Diagnosis, Differential; Endometriosis; Female; Glycolipids; Humans; Lewis X Antigen; Middle Aged; Ovarian Neoplasms

Sialyl SSEA-1 antigen (SLX) is a highly specific tumor marker composed of sugar chain antigens that have Lewis X at their terminals and bind to sialic acid. This antigen is rarely detected in normal tissues, and is present in adenocarcinoma and fetal tissues. We studied the clinical usefulness of SLX in gynecological patients and obtained the following results. (1) The antigen was frequently positive in patients with ovarian cancer with a mean of 89.5 +/- 48.3 U/ml (72.8%, 8/11) and in those with endometriosis with a mean of 39.8 +/- 10.3 U/ml (75.0%, 6/8). (2) Among the gynecological malignancies, the percent positivity was low in those with cervical cancer (20.0%, 5/25), endometrial cancer (33.3%, 1/3), and cancer of the fallopian tube (33.3%, 1/3). (3) The antigen was negative in 20 with myoma uteri, 20 normal pregnant women, and 9 nonpregnant healthy women during the follicular, luteal, or menstrual phase. It was negative in 8 of 9 patients with benign ovarian cyst. False negative results were rare. (4) The SLX level was higher in the ascites than in the serum in patients with ovarian cancer and in those with benign ovarian tumors. (5) The serum SLX in patients with ovarian cancer, which was positive before tumor resection, became negative 2 weeks postoperatively. These results suggest that SLX is a tumor marker with a high specificity to adenocarcinoma of the reproductive organs.

Topics: Adenocarcinoma; Adult; Antigens, Neoplasm; Biomarkers, Tumor; Endometriosis; False Positive Reactions; Female; Genital Diseases, Female; Genital Neoplasms, Female; Glycolipids; Humans; Lewis X Antigen; Menstrual Cycle; Middle Aged; Myoma; Ovarian Neoplasms; Pregnancy; Uterine Cervical Neoplasms; Uterine Neoplasms

The clinical significance of serum sialyl Tn antigen as a tumor marker was evaluated using "STN Otsuka" kits. Results indicated that the antigen was frequently elevated in sera from patients with ovarian cancers (43.1%, 140/325), including serous cystadenocarcinoma (51.6%, 63/122), mucinous cystadenocarcinoma (55.6%, 30/54), endometrioid carcinoma (56.5%, 13/23), and mesonephroid carcinoma (40.0%, 6/15). The positive frequency of sialyl Tn antigen in patients with ovarian carcinoma was less than the frequency of CA 125 (75.5%, 194/257) or sialyl SSEA-1 (47.2% 83/176). However, the false positive rate of sialyl Tn antigen in patients with benign gynecological disorders (3.7%, 15/401) was much lower than the false positive rates of other antigens; such as CA 125 (48.4%, 155/320) and sialyl SSEA-1 (19.2%, 51/266). The serum level of sialyl Tn antigen reflected the clinical activity of the disease quite well in patients with ovarian cancers. The sialyl Tn antigen was concluded to be a useful serum tumor marker for ovarian cancers.

Topics: Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoembryonic Antigen; Cystadenocarcinoma; Endometriosis; Female; Glycolipids; Humans; Lewis X Antigen; Mesonephroma; Ovarian Neoplasms; Radioimmunoassay; Reagent Kits, Diagnostic

A serological diagnosis of ovarian carcinoma was performed using a combination assay consisting of three tumor markers. Cancer Antigen 125 (CA125), Sialyl Lex-i (SLX), and CA72-4. The results were compared with those for the individual tumor markers. Furthermore, the diagnostic accuracy of the combination assay was compared with that of image diagnosis in patients with stage I ovarian carcinoma. 1. The combination assay was positive in 90.3% of the patients with ovarian carcinoma. Classified according to the clinical staging system, the positive rate increased progressively with each stage, 77.6% in stage I, 92.0% in stage II, 98.5% in stage III, and 100.0% in stage IV. According to histological types, the positive rates were 93.8% in serous cystadenocarcinoma, 87.0% in mucinous cystadenocarcinoma, 88.9% in endometrioid carcinoma, and 85.7% in clear cell carcinoma. On the other hand, 6.9% of healthy persons and 38.6% of patients with various benign diseases were found to be false positive in this diagnosis. The high false-positive rate in the latter group is thought to result from the high false-positive rate of 73.5% and 57.1% for adenomyosis and pelvic endometriosis, respectively. 2. The accuracy of the image diagnosis and combination assay was compared in 58 cases with stage I ovarian carcinoma. Both procedures were positive in 38 cases (65.5%). Two cases (3.4%) were positive in image diagnosis but negative in the combination assay. Seven cases (12.1%) were negative in image diagnosis but positive in the combination assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Cystadenocarcinoma; Endometriosis; Female; Glycolipids; Humans; Lewis X Antigen; Neoplasm Staging; Ovarian Neoplasms; Predictive Value of Tests; Tomography, X-Ray Computed; Ultrasonography

The expression of the lacto-N-fucopentaose III (LNF III) epitope by tumor cells of the gastrointestinal tract and ovary has been observed in tissue sections with the use of the murine monoclonal antibody GA 29-1. The presence of the LNF III epitope in the circulation of patients with colorectal cancer has also been reported. In this preliminary study, we describe the presence of LNF III activity in the serum of patients with adenocarcinoma of the ovary. Twelve of 18 (66%) patients with stage I-IV disease demonstrated high reactivity to the GA 29-1 monoclonal antibody. This serum reactivity was independent of disease stage and histologic cell type. In contrast, only 1 of 6 control patients demonstrated a false-positive level of reactivity to GA 29-1. These preliminary results suggest that LNF III warrants further study of its potential application as a serum tumor marker test in patients with adenocarcinoma of the ovary.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Antigens, Neoplasm; Brenner Tumor; Carcinoma, Papillary; Clinical Enzyme Tests; Cystadenocarcinoma; Endometriosis; Female; Humans; Lewis X Antigen; Middle Aged; Oligosaccharides; Ovarian Neoplasms