CA 125 in peritoneal fluid from patients with endometriosis.

This study was performed to evaluate CA 125 in peritoneal fluid as an indicator of endometriosis. Peritoneal fluid from patients with mostly minimal and mild endometriosis (n = 43) and normal controls (n = 17) was collected at laparoscopy or laparotomy. The median concentration of CA 125 in peritoneal fluid did not differ significantly between patients and controls (79 IU/ml versus 76 IU/ml). In patients with endometriosis, a significantly increasing concentration of CA 125 in peritoneal fluid was seen from the early follicular to the late luteal phase; a similar change was not observed in the controls. In 14 patients, peritoneal fluid was sampled again after treatment with danazol and a significant reduction in median CA 125 concentration (76.5 IU/ml versus 57 IU/ml), peritoneal fluid volume (17.5 ml versus 10.5 ml) as well as reduced endometriosis scores (4 versus 2) were found. In controls, the concentration of CA 125 was about 10 times higher in peritoneal fluid than in serum. As the peritoneal levels of CA 125 did not differ significantly between patients with endometriosis and controls and as the reduction seen after danazol treatment did not correlate with the decrease of endometriotic implants, it is concluded that the monitoring of CA 125 in peritoneal fluid will not be useful in the diagnosis or control of endometriosis.     

Salivary progesterone measurements reveal corpus luteum defects which respond poorly to hormonal treatments in operated mild and moderate endometriosis.

Thirty-five women who had been operated on for mild or moderate endometriosis were evaluated through 40 menstrual cycles by daily measurements of salivary progesterone concentrations. As controls, 17 women with normal ovulatory cycles and no endometriosis were studied. In the endometriosis group, 22 cycles were unstimulated, seven were stimulated by clomiphene citrate and 11 with clomiphene citrate, human menopausal gonadotrophin and human chorionic gonadotrophin. A variety of aberrations in profiles of salivary progesterone secretion was detected in all the groups of endometriosis patients and the frequency of normal cycles was significantly lower than in controls (14-18% versus 82%, P less than 0.01). The response to the treatments varied greatly within the groups. In conclusion, the present data demonstrate that patients with endometriosis have a variety of defects in the menstrual pattern of salivary progesterone secretion and that their corpus luteum function responds poorly to stimulatory treatments.     

Preoperative CA125 as a prognostic factor in stage I epithelial ovarian cancer

The purpose of the present study was to evaluate preoperative CA125 as a prognostic factor in stage I epithelial ovarian cancer (EOC). Preoperative serum CA125 levels from 118 women with FIGO (International Federation of Gynaecology and Obstetrics) stage I EOC were analysed and the prognostic value was evaluated and compared with other prognostic factors (age, grade, substages, histologic type). By the Kaplan-Meier estimate we demonstrated that patients with stage I EOC and preoperative serum CA125 levels <65 U/mL had a significantly longer survival compared to stage I EOC patients with preoperative serum CA125 > or = 65 U/mL (p=0.01). The results from the present study may be useful for decision making respecting postoperative chemotherapy in stage I EOC patients. Serum CA125 levels might therefore be included as a prognostic factor in future clinical trials of stage I EOC.     

Measurement of CA125, carcinoembryonic antigen, and alpha-fetoprotein in ovarian cyst fluid: diagnostic adjunct to cytology.

This study used CA125, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) to classify ovarian cysts by measuring the levels of the three antigens; this information was useful when fluid obtained through laparoscopic puncture of ovarian cysts was submitted for cytologic examination from patients for whom tissue was unavailable for classification. We studied 136 consecutive cyst fluids (108 benign, 28 malignant) and correlated the findings with the tissue diagnosis. All three antigens were very low (CEA, less than 0.5 ng/ml; CA125, 55-2,143 mu/ml; and AFP, less than 4.8 ng/ml) in follicular and lutein cysts. Markedly elevated CA125 (296-1,950,000 mu/ml) and low CEA (0.5-220 ng/ml) and AFP (less than 4.8 ng/ml) levels were seen in patients with serous neoplasms, both benign and malignant. Elevated CEA (greater than 600 ng/ml) and CA125 (56-65,330 mu/ml) levels were seen in primary mucinous cystadenoma and cystadenocarcinoma. Two patients with colonic carcinoma metastatic to the ovary had an elevated CEA (greater than 600 ng/ml) and a normal CA125. Only one patient, with a malignant teratoma, had an elevated AFP. The adjunctive use of CEA and CA125 is recommended for the classification of ovarian cysts.     

Use of the concomitant serum dosage of CA 125, CA 19-9 and interleukin-6 to detect the presence of endometriosis. Results from a series of reproductive age women undergoing laparoscopic surgery for benign gynaecological conditions

BACKGROUND: Recent studies have proposed the measurement ofCA 19-9 and IL-6 as an alternative to CA 125 as markers forendometriosis. This study was performed in order to verify theclinical value of serum CA 125, CA 19-9 and IL-6 levels, eitherby themselves or combined, in the detection of the disease.METHODS: In a prospective cohort study, serum concentrationsof CA 125, CA 19-9 and IL-6 were measured in a consecutive seriesof 80 women of reproductive age who underwent laparoscopy forbenign gynaecological pathologies. RESULTS: Endometriosis wasdocumented in 45 women (stage I–II in 14 cases and stageIII–IV in 31 cases). Patients with endometriosis had significantlyhigher levels of CA 125 than controls [23.4 IU/ml (13.3–37.6)versus 11.4 IU/ml (9.1–18.5), P<0.001)]. Conversely,women with and without the disease were shown to have similarlevels of both IL-6 pg/ml [0.6 (undetectable–1.4) versus1.0 pg/ml (0.4–1.9), P=0.09] and CA 19-9 [9.8 IU/ml (4.5–20.8)versus 7.4 IU/ml (2.8–11.5), P=0.11]. The area under thereceiver operating characteristics curve resulted in a statisticallysignificant difference from the null hypothesis only for CA125 (P<0.001). Sensitivity and specificity of CA 125 were27 and 97% respectively and were higher than those related toCA 19-9 and IL-6. Concomitant use of the three dosages led toa sensitivity and a specificity of 42 and 71% respectively.CONCLUSIONS: The concomitant dosage of CA 125, CA 19-9 and IL-6does not add significant information in respect to the CA 125test alone in diagnosing either early or advanced stages ofendometriosis.     

CK7和CA125在人卵巢癌的表达及意义

目的研究细胞角蛋白7(CK7)和CA125联合在卵巢恶性肿瘤中的诊断意义及价值。方法采用免疫组化方法,分别检测100例卵巢肿瘤中CK7和CA125的表达,统计学方法比较两种指标在良性、恶性及转移性肿瘤中的阳性表达率。结果 CK7和CA125在卵巢恶性肿瘤中的表达水平均高于转移源性的卵巢癌和卵巢良性瘤,差异均有统计学意义(0.05)。且在晚期癌中的表达高于早期,差异均有意义(0.05)。结论CK7和CA125过表达提示二者可能参与卵巢癌的发病机制。     

Serum CA 125 in a pregnancy generated by ovum donation

Serum CA 125 was measured by radioimmunoassay during the firsttrimester at intervals of 2 weeks in a woman with Turner‘ssyndrome, who conceived following ovum donation from a healthyanonymous donor. Serum CA 125 concentrations were lower thanor at the 10th percentile of the normal range. These findingsimply that CA 125 may be secreted from the ovary in the firsttrimester, or produced at another site in response to stimulifrom the ovary     

Impaired corpus luteum function and other undesired results of pregnancies associated with inadvertent administration of a long-acting agonist of gonadotrophin-releasing hormone.

Spontaneous pregnancies associated with inadvertent periconceptional administration of long-acting gonadotrophin releasing-hormone agonist (GnRHa), in in-vitro fertilization, occurred in 11 of 161 patients with non-tubal infertility. All these cases exhibited impaired function of the corpus luteum in terms of declining progesterone levels, despite rising levels of human chorionic gonadotrophin. The patients were categorized according to the timing of GnRHa administration: periovulatory (three cases), midluteal (five cases) and late luteal (three cases). Altogether, of the 11 pregnancies, seven ended with a normal livebirth, three with a preclinical gestation and one with a blighted ovum. It appears that spontaneous pregnancies associated with inadvertent administration of GnRHa are not rare. Awareness for early diagnosis and close hormonal monitoring are recommended for the assessment of corpus luteum function and adequate supplementation.     

Fluctuations in CA 125 and CA 15-3 serum concentrations during spontaneous ovulatory cycles

The aim of this study was to investigate cycle dependent changes of serum CA 125 and CA 15-3 concentrations during spontaneous ovulatory cycles. Twenty apparently healthy women with spontaneous menstrual cycles attending our infertility clinic were included. Of these women, 18 had occluded tubes as a result of sterilization. Ovulation was confirmed by luteinizing hormone test and ultrasonography and, to exclude endometriosis, a laparoscopy was performed. Serum samples for CA 125, CA 15-3, 17 beta-oestradiol and progesterone determinations were taken every second day starting on the 2nd day of the cycle until the 7th day of the next cycle. After correction for inter-individual variation in serum concentrations, highest CA 125 concentrations were found during the menstruation. During the follicular and peri-ovulatory phase CA 125 serum concentrations were lowest. For CA 15-3, serum concentrations were not statistically different throughout the cycle. CA 125 and oestradiol concentrations were negatively correlated, CA 15-3 and oestradiol concentrations were positively correlated. Absolute serum concentrations of both CA 125 and CA 15-3 vary among females. Within the female, fluctuations of CA 125 are phase related. In the population studied most of the patients had tubal obstruction and high CA 125 serum concentrations during menstruation, which revokes the theory that the menstrual rise of CA 125 is due only to retrograde menstruation.     

Influence of human chorionic gonadotrophin, oestradiol and progesterone on uteroplacental and corpus luteum blood flow in normal early pregnancy.

A transvaginal colour and pulsed Doppler study was performed on 44 women with normal pregnancies between 5 and 16 weeks of gestation. Maternal levels of human chorionic gonadotrophin (HCG), free alpha-HCG subunit, free beta-HCG subunit, 17 beta-oestradiol and progesterone were determined in sera obtained at the time of Doppler examination. Uterine peak systolic velocity (PSV) and alpha-HCG and 17 beta-oestradiol levels increased significantly (P < 0.001) from the second to the fourth month of gestation, whereas uterine and spiral resistance index (RI) decreased significantly (P < 0.005 and P < 0.001, respectively) with gestational age. Levels of HCG and beta-HCG peaked significantly (P < 0.01) during the third month of gestation. Corpus luteum PSV and RI and progesterone levels did not vary significantly with gestational age. Multiple regression analysis showed that gestational age was the only significant (P < 0.05) contributor to uterine PSV and spiral RI variability. In addition to gestational age, 17 beta-oestradiol had a significant (P < 0.001) influence on uterine RI. Both corpus luteum PSV and RI were significantly (P < 0.01 and P < 0.05, respectively) related to progesterone levels. Corpus luteum PSV was also significantly (P < 0.05) related to 17 beta-oestradiol levels and RI to HCG levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Peripheral CA 125 levels in patients with uterine fibroids.

CA 125, a marker of ovarian cancer, is also increased in otherwise normal women suffering from, for example, pelvic inflammatory disease, endometriosis and adenomyosis. The tissues suspected of producing CA 125 in normal women include the endometrium, the ovary and the peritoneum. This study was based on the hypothesis that uterine myomata would distend the peritoneum covering the uterus and thereby increase the peripheral levels of CA 125. To verify this hypothesis we measured CA 125 by an immunoradiometric assay in eight normal women every second day throughout the cycle and in 26 women with uterine fibroids before and after hysterectomy and at 8 and 12 weeks during gonadotrophin releasing hormone (GnRH) analogue therapy. In normal women no difference was observed between CA 125 levels in the follicular phase or in the luteal phase of the cycle. Over one-third (10/26) of the patients with uterine fibroids had increased (greater than 90th centile of the controls) levels of CA 125 before GnRH therapy or hysterectomy. Removal of the uterus or administration of GnRH significantly decreased peripheral concentrations of CA 125 to levels below those observed in normal women. Furthermore, a significant positive correlation was observed between the levels of CA 125 and the volume of myomata as assessed by ultrasound. We conclude that in those cases of uterine fibroids where CA 125 is increased, monitoring this parameter during GnRH therapy is a good indirect measurement of regression of myomata.     

Peritoneal natural killer cells from epithelial ovarian cancer patients show an altered phenotype and bind to the tumour marker MUC16 (CA125)

The ovarian tumour marker MUC16 (CA125) inhibits the cytotoxic responses of human natural killer (NK) cells and down-regulates CD16. Here we show that approximately 10% of the peripheral blood NK cells (PBNK) from the epithelial ovarian cancer (EOC) patients are CD16(-) CD56(br) whereas 40% of the peritoneal fluid NK (PFNK) carry this phenotype, which is usually associated with NK cells from the lymph nodes or human decidua. PBNK from healthy donors exposed to PF show a significant increase in the CD16(-) CD56(br) population. This shift in phenotype is not caused by increased apoptosis of the CD16(+) CD56(dim) cells or selective proliferation of the CD16(-) CD56(br) NK cells. Thus, the terminal differentiation of the CD16(-) CD56(br) NK cells to CD16(+) CD56(dim) subset that occurs during normal NK cell development may actually be a reversible step. A majority of the NK cell receptors (NKp46, NKp44, NKG2D, CD244, CD226, CD158a, CD158b, and CD158e) studied were down-regulated in the PFNK. MUC16 binds selectively to 30-40% of CD16(+) CD56(dim) NK cells in EOC patients indicating that phenotypic alterations in these cells are mediated by tumour-derived soluble factors. Similar to EOC, MUC16 in early pregnancy also binds to NK cells suggesting shared mechanisms of NK cell suppression in feto-maternal tolerance and immune evasion by ovarian cancers.     

Angiogenesis in the human corpus luteum: simulated early pregnancy by HCG treatment is associated with both angiogenesis and vessel stabilization.

BACKGROUND: This study examined changes in the luteal vasculature throughout the menstrual cycle and during simulated pregnancy with human chorionic gonadotrophin (HCG) in the human. METHODS: Endothelial cell and pericyte area were assessed by quantitative immunocytochemistry for CD34 and alpha-smooth muscle actin respectively, taking into consideration the dynamics of lutein cell hypertrophy and atrophy throughout the cycle and after HCG treatment. Endothelial cell proliferation was detected by Ki-67/CD34 dual staining and a proliferation index was obtained. The molecular regulation of angiogenesis was studied by examining changes in vascular endothelial growth factor (VEGF) immunostaining. RESULTS: The early luteal phase is associated with intense angiogenesis, as indicated by high endothelial cell proliferation, and by the mid-luteal phase a mature vasculature was apparent, as shown by maximal endothelial cell and pericyte areas. During the late luteal phase, decreased endothelial proliferation, endothelial cell and pericyte area indicated vascular regression. HCG treatment induced a second burst of total and endothelial cell proliferation and a concomitant increase in endothelial cell and pericyte areas. VEGF protein was expressed throughout the luteal phase and a significant increase was found after HCG treatment. CONCLUSION: Luteal rescue with HCG is associated with a second wave of angiogenesis and vascular stabilization.     

Characterization of the CA125 Antigen Secreted from a Newly Established Human Ovarian Cancer Cell Line (SHIN-3)

A cell line (designated SHIN 3) was established from a 56-year old Japanese woman diagnosed as having serous cystadenocarcinoma of the ovary. SHIN 3 produced the tumor marker, CA125. When samples were subjected to one dimensional gel electrophoresis followed by immunoblotting with anti CA125 antibody, antigen binding appeared in the low-molecular mass fraction around 50 KDa as well as in the high molecular-mass fraction (more than 200 KDa). Subsequent resolution of this lower molecular-mass component by two dimensional gel electrophoresis gave rise to bands of 49 KDa near an isoelectric point of 7.3. Treatment of the CA125 antigen with 10 mM periodic acid resulted in no loss of activity. However, reduction and alkylation in 6 M guanidine HCI or treatment at 100 C for 20 min resulted in complete loss of activity. Treatment with various glycosidases did not inhibit activity, whereas digestion with proteases (except for papain) produced complete loss of activity, suggesting that the CA125 antigenic determinant is composed of con-formationally dependent peptides.     

Soluble adhesion molecules in serum and cyst fluid from patients with cystic tumours of the ovary

The potential of the soluble forms of the adhesion moleculesICAM-1 (sICAM-1), CD44std (sCD44std) and E-cadherin (sE-cadherin)was tested for the diagnosis of benign and malignant cysticepithelial tumours of the ovary. Concentrations of sICAM-1,sCD44 std and sE-cadherin were measured by enzyme-linked immunosorbentassay (ELISA) in the serum and cyst fluid obtained from 23 patientswith luteal cysts, 29 with cystadenomas, nine with dermoid cysts,five with borderline tumours and 11 with carcinomas. Serum concentrationsof sICAM-1, but not of sCD44std and sE-cadherin, were constantlyelevated compared with normal controls. Cyst fluid concentrationsof sICAM-1, sCD44std and sE-cadherin were elevated in borderlineand malignant tumours compared with cystadenomas (P = 0.034,0.006 and 0.001, respectively). In conclusion, our results suggestthat serum concentrations of adhesion molecules have no diagnosticvalue in ovarian tumours, whereas cyst fluid concentrationsmay facilitate distinction between benign lesions and borderlineor malignant tumours.     

Endocrinology: Repeated aspiration of ovarian follicles and early corpus luteum cysts in an in-vitro fertilization programme reduces the risk of ovarian hyperstimulation syndrome in high responders

A retrospective analysis of ovarian hyperstimulation syndromein high responders undergoing in-vitro fertilization (IVF) ispresented. High responders were defined as having > 20 folliclesand serum oestradiol > 3000 pg/ml after treatment with humanmenopausal gonadotrophin. Of the initial 30 IVF cycles in highresponders, 23 developed a moderate-to-severe ovarian hyperstimulationsyndrome (76.7%). Subsequently, 15 other IVF cycles in highresponders were combined with a repeated aspiration of ovarianfollicles and corpus luteum cysts just prior to embryo transfer.Only three patients (20%) developed a moderate ovarian hyperstimulationsyndrome (P = 0.0004). We conclude that repeated follicularaspiration is safe and results in a significant reduction inthe incidence and severity of this condition in high respondersundergoing IVF.     

CA125 and thyroglobulin staining in papillary carcinomas of thyroid and ovarian origin is not completely specific for site of origin

AIMS: A 70-year-old woman presented with metastatic psammoma body-rich papillary carcinoma in a supraclavicular lymph node. No primary site was evident. The tumour showed strong staining for CA125 and weak staining for thyroglobulin. Prompted by this case we aimed to assess the reliability of immunostaining for CA125 and thyroglobulin in making the distinction between thyroid and ovarian papillary carcinoma. METHODS AND RESULTS: Nine papillary carcinomas of the thyroid and 17 serous papillary carcinomas of the ovary were stained for CA125 and thyroglobulin, as well as CAM 5.2, LP 34, carcinoembryonic antigen (CEA), S100 and diastase/periodic acid-Schiff. Nine of nine thyroid carcinomas stained for thyroglobulin; in addition CA125 was positive in four of nine. Normal surrounding thyroid also showed some reaction. Seventeen of 17 ovarian serous carcinomas were positive for CA125; in addition one case showed moderately strong staining for thyroglobulin. Mucin stains were positive in 14/17 ovarian serous carcinomas, but negative in all thyroid carcinomas. The other antibodies assessed showed no useful differences in staining frequency. Conclusion: Many cases of papillary carcinoma of the thyroid show CA125 staining, and this feature therefore has little positive predictive value for an ovarian origin. Occasional cases of ovarian papillary carcinoma may show staining for thyroglobulin, and this result should therefore be interpreted cautiously.     

Antitumor activity of specific immunotherapy with mucin containing CA 125 antigen in mice with CaO 1 ovarian carcinoma

Experiments in CBA mice with transplanted CaO 1 ovarian carcinoma possessing common antigenic determinants with human ovarian carcinoma showed that specific immunotherapy with mucin containing CA 125 antigen inhibited tumor growth by 60% and prolonged antimal lifespan by 40–60% in comparison with the control. The correlation coefficient between the tumor size and antibody titer after injection of mucin was −0.4 for IgM and −0.6 for IgG. Titration of IgG may be used for monitoring of the efficiency of specific immunotherapy. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 4, pp. 456–458, April, 2000     

Serum and cyst fluid levels of interleukin (IL) -6, IL-8 and tumour necrosis factor-alpha in women with endometriomas and benign and malignant cystic ovarian tumours

BACKGROUND: Altered expression of cytokines has been suggested as a specific event for the maintenance and progression of endometriomas. Few data exist on cytokine expression in endometriomas compared with benign and malignant ovarian tumours. Hence, serum and cyst fluid levels of interleukin (IL)-6, IL-8 and tumour necrosis factor-alpha (TNF-alpha) were evaluated in women with endometriomas and compared with those in women with benign or malignant ovarian tumours. METHODS: Investigations included immunoradiometric determination of serum and cyst fluid concentrations of IL-6, IL-8 and TNF-alpha in 34 women with endometriomas, 30 women with benign and 13 women with malignant cystic ovarian tumours. RESULTS: Serum IL-6 levels were higher in ovarian cancer than in endometriomas (P<0.01) or benign tumours (P<0.01). Serum TNF-alpha levels differed between benign tumours and endometriomas (P<0.01), but not between endometriomas and malignant tumours. Cyst fluid levels of IL-8 were higher in endometriomas than in benign tumours (P<0.001) and lower than in malignant tumours (P=0.03). Cyst fluid levels of TNF-alpha differed between malignant tumours and endometriomas (P<0.01) and benign tumours (P<0.01), but not between endometriomas and benign tumours. In the endometriomas group, a positive correlation was found between serum and cyst fluid levels of IL-6 (P=0.003, rho=0.633), and between serum levels of IL-6 and IL-8 (P=0.03, rho=0.415). CONCLUSIONS: Endometriomas were associated with serum TNF-alpha levels similar to those found in women with ovarian cancer, while serum IL-6 levels and cyst fluid IL-8 levels were intermediate between those observed in benign and malignant ovarian tumours.