卵巢上皮性肿瘤组织中KiSS-1、基质金属蛋白酶9和核因子κBp65蛋白的表达及其相关性

目的 探讨KiSS-1、基质金属蛋白酶9（MMP-9）、核因子κB（NF-κB）p65蛋白3者在卵巢上皮性肿瘤组织中的表达及其相关性。方法 采用免疫组化方法检测50份卵巢上皮性癌（卵巢癌）、20份卵巢交界性肿瘤、20份卵巢良性肿瘤和10份正常卵巢组织中KiSS-1、MMP-9、NF-κBp65蛋白的表达,并分析其临床意义及3者间的相关性。结果 KiSS-1蛋白在卵巢癌组织中的阳性表达率（80％）明显高于良性肿瘤组织及正常卵巢组织（分别为35％、10％;P〈0．05）;在卵巢交界性肿瘤组织中阳性表达率（65％）明显高于正常卵巢组织（P〈0．05）。在卵巢癌组织中,KiSS-1蛋白阳性表达率与淋巴结转移有关（P〈0．05）,与手术病理分期、病理类型及病理分级均无关（P〉0．05）;MMP-9蛋白阳性表达率与手术病理分期及淋巴结转移有关（P〈0．05）,而与病理类型及病理分级均无关（P〉0．05）;NF-KBp65蛋白阳性表达率与手术病理分期、病理分级及淋巴结转移有关（P〈0．05）,而与病理类型无关（P〉0．05）。在卵巢癌组织中,KiSS-1与MMP-9、NF．KBp65蛋白表达呈显著负相关关系（rs=-0．547,P〈0．05;rs=-0．414,P〈0．05）;MMP-9与NF-κBp65蛋白表达呈显著正相关关系（rs=0．695,P〈0．05）。结论 KiSS-1基因可能对卵巢癌的转移起一定的抑制作用;KiSS-1基因可能通过抑制MMP-9、NF-κB基因,从而发挥抑制卵巢癌转移的作用。     

NGAL和MMP-9在卵巢上皮性癌中的表达及相关性研究

目的:检测中性粒细胞明胶酶相关载脂蛋白(NGAL)和基质金属蛋白酶-9(MMP-9)在卵巢上皮性肿瘤组织和血清中的表达,了解两者与卵巢癌临床病理特征的关系。方法:应用半定量RT-PCR和ELISA法检测50例上皮性卵巢癌、21例卵巢良性肿瘤和18例正常对照的卵巢组织和血清中NGAL和MMP-9的表达水平。结果:(1)卵巢癌组的组织及血清中NGAL和MMP-9表达明显高于卵巢良性肿瘤组和正常对照组(P均<0.05);二者的高表达与临床分期、淋巴结转移正相关(P均<0.05);卵巢癌患者的组织及血清中NGAL与卵巢癌的组织分化程度正相关(P均<0.05),MMP-9则与卵巢癌的组织分化程度负相关(P均<0.05)。(2)卵巢癌患者的组织或血清中,NGAL表达均与MMP-9表达呈正相关(r=0.740,r=0.676,P均<0.05)。结论:NGAL和MMP-9在卵巢上皮性癌中表达上调,可能与卵巢上皮性癌的发生、发展有关。     

Use of serum secretory leukocyte protease inhibitor levels in patients to improve specificity of ovarian cancer diagnosis

OBJECTIVE: To assess the clinical relevance of serum secretory leukocyte protease inhibitor (SLPI) levels in distinguishing patients with ovarian cancers from those with benign ovarian cysts, we determined concentrations with reference to the FIGO stage and other clinical characteristics. METHODS: Preoperative serum SLPI levels were measured in women with invasive epithelial ovarian cancer (n = 55), benign ovarian cysts (n = 25), or normal controls (n = 38) using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum SLPI concentration was significantly elevated in the ovarian cancer patients (median 67 ng/ml, interquartile range 26-124 ng/ml) as compared to the benign cyst patients (37 and 25-66 ng/ml) or healthy women (32 and 25-43 ng/ml). Using an SLPI cutoff of 50 ng/ml and a CA125 cutoff of 30 units/ml, with both markers elevated the sensitivity was 95%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 89% between the malignant and benign cyst patients. CONCLUSION: Serum SLPI levels could be useful for differentiating benign ovarian cysts from malignancies and to improve the specificity of diagnosis.     

Elevated serum RANTES levels in patients with ovarian cancer correlate with the extent of the disorder

OBJECTIVE: To assess the clinical relevance of serum regulated upon activation, normal T-cell expressed and secreted (RANTES) levels in distinguishing patients with ovarian cancers from those with benign ovarian cysts, we measured its concentration with reference to the disease stage, pathological grading, histological subtype, and the residual tumor mass. METHODS: Preoperative serum RANTES levels were measured in women with invasive epithelial ovarian cancer (n = 52), borderline ovarian tumor (n = 6), benign ovarian cysts (n = 28), or normal controls (n = 12) using an enzyme-linked immunosorbent assay. RESULTS: The serum RANTES concentration was significantly elevated in the ovarian cancer patients (median 53 ng/ml, interquartile range 23-104 ng/ml) compared to the benign ovarian cyst patients as controls (38 ng/ml, 5-72 ng/ml) values correlating with the stage of disease and the extent of residual tumor mass. No significant correlation between CA125 and RANTES in the serum was observed in either the controls or the ovarian cancer patients. Using a RANTES cutoff of 45 ng/ml and a CA125 cutoff of 35 units/ml, when either marker was elevated, the specificity improved 94%. CONCLUSION: Our study suggest that preoperative serum RANTES levels may be useful in differentiating benign ovarian tumors from malignancy correlating with the extent of the disorder.     

Elevation of serum interleukin-1 receptor antagonist levels in women with gynaecological cancers

This study included 15 patients with gynaecological cancers (7 with cervical cancer, 6 with endometrial cancer, and 12 with ovarian cancer); 7 with benign gynaecological disorders (5 with benign ovarian tumour and 2 with uterine myoma); and 10 healthy women as a control group. Serum interleukin-1 receptor antagonist (IL-1 ra) levels in patients with gynaecological cancer were significantly higher than those in patients with benign gynaecological disorders (P = 0.04) and in healthy controls (P = 0.0009). IL-1 ra may play an important role in host immune responses in local and general environments against gynaecological cancers.     

Significance of immunosuppressive acidic protein in the diagnosis and follow-up of patients with ovarian cancer, in particular as a marker for chemotherapeutic effects

Serum immunosuppressive acidic protein (IAP) was determined in patients with ovarian cancer and was examined as a marker for ovarian cancer when, chemotherapy in particular, was applied. Samples were sera obtained from 68 ovarian cancers, 74 benign ovarian tumors, 54 cervical cancers, 57 uterine myomas and 88 healthy controls. Elevated levels of IAP were found in 89.5% of patients with ovarian cancer and this high positive ratio was not affected by tumor histologic features. The measurement of the serum IAP level is useful for the initial diagnosis of ovarian cancer because of low false positive rates (8.1%) in benign ovarian tumors and high positive rates even in the early stage of ovarian cancer. Serial determinations of serum IAP levels were well correlated with the response to the treatment (chemotherapy in particular) and the prognosis of cancer patients, even in the case of patients with leucocytopenia induced by the intensive chemotherapy. In case of recurrent patients (whose lesions were observed in the intraperitoneal space), IAP values tended to increase earlier than other conventional tumor-derived markers. Therefore, IAP may also be a useful follow-up marker for patients with ovarian cancer (particularly, for the early detection of recurrence).     

Clinical significance of new tumor marker CA 125 in gynecological cancer--particularly usefulness in diagnosis of ovarian cancer

A concentration in sera of a new antigen CA125 related to cancer of the ovary was measured by radioimmunoassay which used a monoclonal antibody, and its usefulness as a tumor marker in the diagnosis of cancer of the ovary was investigated. The mean values for CA125 in sera of healthy controls (80 females) were 14.2 +/- 12.2 U/ml. Mean values for CA125 in sera of various patients were 29.0 +/- 39.6 for myoma uteri (30 cases), 26.7 +/- 30.1 for benign ovarian tumors (10 cases), 64.4 +/- 146.2 for cervical carcinoma (14 cases), and 31.5 +/- 19.8 for endometrial carcinoma (6 cases), whereas the mean values for ovarian cancers (23 cases) were as high as 311.3 +/- 250.4. On the other hand, positive rates for CA125, when the cut-off value was set to 65 U/ml, were 1.3% for healthy controls (1 out of 80 cases), 10.0% for myoma uteri (3 out of 30 cases), 10.0% for benign ovarian tumors (1 out of 10 cases), 14.3% for cervical carcinoma (2 out of 14 cases), and 16.7% for endometrial carcinoma (1 out of 6 cases), whereas the positive rate for ovarian cancers was 78.3% (18 out of 23 cases). Especially for serous cystadenocarcinoma, the positive rate was 100% (10 out of 10 cases). From the above, the measurement of CA125 in sera was considered to be significant in the diagnosis of ovarian cancer.     

The clinical significance of tissue polypeptide antigen (TPA) in the patients with gynecologic tumor

In order to estimate the clinical significance of tissue polypeptide antigen (TPA), TPA was measured by radioimmunoassay in sera from patients with various gynecological tumors. They were 40 uterine myomas, 94 cervical cancers, 21 endometrial cancers, 3 vulval cancers, 51 benign ovarian tumors and 78 malignant ovarian tumors including 18 low potential malignant tumors (LPM). The mean TPA values in patients with benign as well as malignant tumors were significantly higher than that of 97 healthy volunteers (68 +/- 17 U/l; Upper limit; 107 U/l). Among the cervical cancer patients, serum TPA level and positive ratio became higher as the disease progressed. In the advanced cases, the mean serum TPA value and positive ratio were 149 +/- 64 U/l and 75%, respectively. The mean TPA value in the endometrial cancer patients was significantly higher than that of myoma patients. Among the patients with ovarian tumor, serum TPA was elevated in 14% of benign cases, 28% of LPM cases, 47% of stage I cases and 82% of the advanced cases. Serum TPA values varied directly with the stage and malignancy of disease. The present study revealed that TPA is a useful markers in the diagnosis of gynecological tumors, especially for ovarian cancers.     

The role of ultrasound evaluation in the detection of early-stage epithelial ovarian cancer

OBJECTIVE: Epithelial ovarian cancer kills more women than all other gynecologic malignancies combined because of our inability to detect early-stage disease. Ultrasonography has demonstrated usefulness in the detection of ovarian cancer in asymptomatic women, but its value for the detection of early-stage epithelial ovarian cancer in women of increased risk is uncertain. We examined the usefulness of sonography in the detection of early-stage epithelial ovarian cancer in asymptomatic high-risk women who participated in the National Ovarian Cancer Early Detection Program. STUDY DESIGN: Only asymptomatic women of increased risk for the development of ovarian cancer with initial normal gynecologic and ultrasound examinations were eligible to participate in the institutional review board-approved National Ovarian Cancer Early Detection Program. Participants underwent comprehensive gynecologic and ultrasound examinations every 6 months. Increased risk includes women with at least 1 affected first-degree relative with ovarian cancer; a personal history of breast, ovarian, or colon cancer; > or =1 affected first- and second-degree relatives with breast and or ovarian cancer; inheritance of a breast cancer mutation from an affected family member, or membership within a recognized cancer syndrome. RESULTS: The average age of the 4526 women who were evaluated was 46 years; 2610 women were premenopausal, and 1916 women were postmenopausal. A total of 12,709 scans have been performed since 1990. Visualization of both ovaries was noted in 98% of premenopausal and in 94% of postmenopausal women. Fourteen women had undergone unilateral salpingo-oophorectomy. Recall rates at less than the routine 6-month interval were 0.4% in the premenopausal and 0.3% in postmenopausal women. A total of 98 women with persistent adnexal masses were identified, and 49 invasive surgical procedures were performed that diagnosed 37 benign ovarian tumors and 12 gynecologic malignancies. All cancers were detected in asymptomatic women who had normal ultrasound and physical examinations 12 and 6 months before the cancer diagnosis. The detected malignancies were fallopian tube carcinoma (stage IIIC; n = 4 women), primary peritoneal carcinoma (n = 4 women; stage IIIA, 1 woman; stage IIIB, 2 women; stage IIIC, 1 woman), epithelial ovarian cancer (stages IIIA and IIIB; n = 2 women), and endometrial adenocarcinoma (stage IA; n = 2 women). Additionally 37 primary and 12 recurrent breast carcinomas were detected by physical examination. A total of 184 women with genetic predisposition (breast cancer positive) have undergone a prophylactic bilateral salpingo-oophorectomy; 23% of these procedures found atypical hyperplasia, and unexpectedly, 2 women (1%) were found to have stage III (A and B) primary peritoneal carcinoma. CONCLUSION: This study demonstrates the limited value of diagnostic ultrasound examination as an independent modality for the detection of early-stage epithelial ovarian cancer in asymptomatic women who are at increased risk for disease.     

Expression of latent matrix metalloproteinase 9 (MMP-9) predicts survival in advanced ovarian cancer

OBJECTIVE: Matrix metalloproteinases (MMPs) are frequently expressed in malignant tumors and play an important role in tumor invasion and metastasis. MMP-2 and MMP-9 expression has been correlated with poor survival in some tumors, but data for ovarian cancer are lacking, despite clinical trials with MMP inhibitors. The aim of this study was to assess activity of MMP-2 and MMP-9 and correlate it to prognosis in ovarian cancer. METHODS: MMP-2 and MMP-9 gelatinolytic activity was analyzed in 84 patients with advanced ovarian cancer FIGO stage III and 19 benign ovarian tumors by gelatin zymography. MMP-9 immunoreactivity was detected by immunohistochemistry and gelatinolytic activity was localized in ovarian cancer tissue by in situ zymography. RESULTS: were correlated with patient survival, with a median follow-up period of 55 months. Results. Median pro-MMP-9 activity was at 0.00 U/microg protein in benign ovarian tissues and 4.82 U/microg protein in ovarian cancer (P = 0.001); activated MMP-9 was not detected. Pro-MMP-2 expression in benign ovarian tissue did not differ from that of malignant ovarian tissue, whereas active MMP-2 was present in 52% of ovarian cancers, but absent in benign ovarian tissues. Analyzing all patients high pro-MMP-9 activity was associated with short overall survival (P = 0.019) while pro-MMP-2 and activated MMP-2 did not predict overall survival. When analyzing the subgroups of patients with and without residual tumor mass at the time of surgery, pro-MMP-9 was of prognostic value only in the subgroup of patients with no residual tumor mass. In univariate analysis pro-MMP-9 activity, residual tumor mass, age, ascites volume, and grading were of prognostic significance for overall survival. However, in multivariate analyses, including all biological and clinicopathologic variables, only pro-MMP-9 and residual disease remained statistically independent prognostic factors. In situ zymography localized gelatinolytic activity predominantly to the tumor cell nests displaying MMP-9 immunoreactivity. CONCLUSIONS: Pro-MMP-9 gelatinolytic activity, but not active MMP-2 or MMP-9, serves as a useful statistically independent prognostic factor in ovarian cancer FIGO stage III, thus helping to identify ovarian cancer patients with an aggressive form of the disease.     

Soluble urokinase plasminogen activator receptor in preoperatively obtained plasma from patients with gynecological cancer or benign gynecological diseases

OBJECTIVE: The present study was planned to measure preoperative levels of soluble urokinase plasminogen activator receptor (suPAR) in plasma from patients with gynecological diseases, and to test for a relationship to clinical and biochemical patient characteristics. METHODS: Using a specific and sensitive kinetic ELISA, suPAR levels were determined in preoperative citrate plasma samples from 53 ovarian, 34 endometrial, and 30 cervical cancer patients, 17 patients with benign ovarian tumors, and 28 patients with benign endometrial diseases. In addition, suPAR was measured in citrate samples from 31 female blood donors. RESULTS: suPAR was measurable in all samples. No significant difference was found between plasma suPAR in the blood donors and the patients with benign diseases (P = 0.58). The groups of cancer patients had suPAR levels that were significantly higher than those found in the blood donors (P < 0.0001, P < 0.0001, and P = 0.001 for patients with ovarian, endometrial, and cervical cancer, respectively). In all groups of cancer patients a trend toward increasing suPAR levels with increasing FIGO stage was noted (P = 0.0003, P = 0.02, and P = 0.01 for patients with ovarian, endometrial, and cervical cancer, respectively). Using the median suPAR level to dichotomize the ovarian cancer patients, FIGO stages I-III, a significantly increased risk of progression/relapse was found for patients with high suPAR levels (Hazard ratio (HR) = 3.1, 95% CI: 1.1-8.8, P = 0.03). A multivariate analysis was performed, including suPAR, FIGO stage, and CA-125. Only FIGO stage III compared with FIGO stage I was significant (HR = 15, 95% CI: 1.8-129, P = 0.01). Survival analyses were not performed in the endometrial or cervical cancer patients due to few progressions/relapses during the follow-up period. CONCLUSION: This study concludes that patients with gynecological cancers have elevated plasma suPAR levels as compared with healthy female blood donors and patients with benign gynecological diseases. In addition, high preoperative plasma levels of suPAR are significantly associated with poor outcome of ovarian cancer patients. However, additional studies are needed to further validate the clinical usefulness of plasma suPAR measurements in the management of ovarian cancer patients.     

Differential diagnosis of ovarian cancer, benign ovarian tumor and endometriosis by a combination assay of serum sialyl SSEA-1 antigen and CA125 levels

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.     

The role of D-dimer in diagnosis of ovarian cancer

One of fibrin degradation products, D-dimer was measured in ovarian cancer (N = 28), benign ovarian tumors (N = 26), benign uterine tumors (N = 15) and normal controls (N = 66). The D-dimer value for ovarian cancers was 721 +/- 423 ng/ml, benign ovarian tumors; 299 +/- 248, benign uterine tumors; 248 +/- 141, and normal controls; 237 +/- 212, respectively. There was a significant difference between the ovarian cancer group and the other groups (p less than 0.01). When the cut off level of D-dimer was less than 400 ng/ml, the positive rate for D-dimer was 50% in stage I of ovarian cancer, 88% in stage II, 86% in stage III and 80% in stage IV. Overall, 82% of ovarian cancer patients were positive. D-dimer provides good sensitivity compared with other ovarian cancer markers such as TPA, SLX and CEA. The coefficient correlation between D-dimer and CA125, TPA, SLX or CEA was 0.476, 0.376, 0.226, -0.292, respectively. This suggest that the measurement of D-dimer is useful in diagnosing ovarian cancer.     

B7-H4 is over-expressed in early-stage ovarian cancer and is independent of CA125 expression

OBJECTIVE: This study characterizes the expression of the novel biomarker B7-H4 in ovarian cancer tissue, normal ovaries, and benign ovarian tumors, and evaluates its relationship to CA125. METHODS: Ovarian tissue lysates from 251 patients with ovarian carcinoma were assessed for the levels of B7-H4 and CA125 by ELISA assays. For comparison, ovarian tissues from patients with benign ovarian tumors (n=43) and patients with normal ovaries (n=32) were tested. The marker concentrations were correlated with CA125 expression, clinicopathological variables, and patient outcome. RESULTS: Using a cut-off based on the 95th percentile of B7-H4 or CA125 concentration in the control group, B7-H4 was over-expressed in 48% of patients with stage I cancer, 55% of patients with stage II cancer, and 67% of patients with late stage cancer. CA125 was elevated in 31% patients with early stage cancer. B7-H4 was elevated in tumors of 30 patients with early stage cancer that were negative for CA125. The combination of B7-H4 and CA125 identified 56 early stage cancer patients (65%) as positive. Correlation of marker expression to clinical outcome showed that high B7-H4 levels were correlated with poor prognosis. However, the effect was not significant when outcome was adjusted for other clinicopathological variables. CONCLUSION: B7-H4 expression was low in normal ovaries and in benign tumors while half of early stage and two-thirds of late stage cancers over-expressed B7-H4. The data are consistent with previous observations and support further investigation of B7-H4 in the detection of early stage ovarian cancer either alone, or in combination with CA125.     

Synchronous primary cancers of the endometrium and ovary: a single institution review of 84 cases

OBJECTIVES: Synchronous primary cancers of the endometrium and ovary are found in 10% of women with ovarian cancer and 5% of women with endometrial cancer. The purpose of this study was to characterize patients diagnosed with synchronous primary cancers of the endometrium and ovary with an emphasis on risk factors. METHODS: Between 1989 and 2002, 84 patients with synchronous primary cancers of the endometrium and ovary were identified. Patients with uterine papillary serous carcinoma were excluded. Clinical and pathologic information was obtained from medical records. Parametric methods were used to compare clinical and pathologic features. Kaplan-Meier survival analyses were performed and compared using the log rank test. RESULTS: Median age at diagnosis was 50 years. Median body mass index (BMI) was 28 kg/m(2). Fifty-one percent (43/84) of the women were premenopausal and 33% (28/84) were nulliparous. The most common presenting symptom was abnormal vaginal bleeding; in those women with abnormal vaginal bleeding, 69% had stage I ovarian cancer. Ovarian cancer was an incidental finding in 48% of these patients. Sixty-eight percent of patients (57/84) had endometrioid histology of both their endometrial and ovarian cancers. Patients with early stage ovarian cancer tended to have a more favorable prognosis than those with advanced stage disease (median survival not reached in stage I and II versus 66 months in stage III and IV, P = 0.06). Patients with concordant endometrioid histology had a favorable prognosis (median survival 119 versus 48 months in all other groups, P = 0.02). CONCLUSIONS: In this large series of patients, women with synchronous primary cancers of the endometrium and ovary were young, obese, nulliparous, and premenopausal. Patients with concordant endometrioid tumors of the endometrium and ovary had a favorable prognosis, with median survival approaching 10 years.     

Investigation of women with endometrial carcinoma using serum vascular endothelial growth factor (VEGF) measurement

Abstract. Gornall RJ, Anthony FW, Coombs EJ, Hogston P, Woolas RP. Investigation of women with endometrial carcinoma using serum endothelial growth factor (VEGF) measurement.
This study assessed whether serum VEGF measurement in women presenting with endometrial cancer could predict advanced stage disease. Preoperative sera from 37 women undergoing laparotomy for suspected endometrial cancer were assayed for VEGF, CA125 and platelet count. Significant positive correlation was shown between VEGF and platelet levels ( P = 0.003, r = 0.477). However, no correlation was demonstrated between VEGF and stage overall, and no significant difference was shown between those with early (stage 1A/1B, n = 20) compared to those with advanced (stage >1B, n = 13) or disseminated (stage >2, n = 7) disease. Serum VEGF measurement was not beneficial in the preoperative assessment of stage in patients with endometrial carcinoma. Strong correlation with platelet levels suggests that this is one of the sources of VEGF measured.     

Urinary interleukin-1β levels among gynecological patients

Background

Early detection of epithelial ovarian cancer (OC) is necessary to overcome the high mortality rate of late stage diagnosis; and, examining the molecular changes that occur at early disease onset may provide new strategies for OC detection. Since the deregulation of inflammatory mediators can contribute to OC development, the purpose of this pilot study was to determine whether elevated urinary levels of Interleukin-1beta (IL-1 beta) are associated with OC and associated clinical parameters.

Methods

Urinary and serum levels of IL-1 beta were analyzed by ELISA from a patient cohort consisting of healthy women (N = 10), women with ovarian benign disease (N = 23), women with OC (N = 32), women with other benign gynecological conditions (N = 22), and women with other gynecological cancers (N = 6).

Results

Average urinary IL-1 beta levels tended to be elevated in ovarian benign (1.26 pg/ml) and OC (1.57 pg/ml) patient samples compared to healthy individuals (0.36 pg/ml). Among patients with benign disease, urinary IL-1β levels were statistically higher in patients with benign inflammatory gynecologic disease compared to patients with non-inflammatory benign disease. Interestingly, urinary IL-1 beta levels tended to be 3-6x greater in patients with benign ovarian disease or OC as well as with a concomitant family history of ovarian and/or breast cancer compared to similar patients without a family history of ovarian and/or breast cancer. Lastly, there was a pattern of increased urinary IL-1 beta with increasing body mass index (BMI); patients with a normal BMI averaged urinary IL-1 beta levels of 0.92 pg/ml, overweight BMI averaged urinary IL-1 beta levels of 1.72 pg/ml, and obese BMI averaged urinary IL-1 beta levels of 5.26 pg/ml.

Conclusions

This pilot study revealed that urinary levels of IL-1 beta are elevated in patients with epithelial OC supporting the thought that inflammation might be associated with cancer progression. Consequently, further studies of urinary IL-1 beta and the identification of an inflammatory profile specific to OC development may be beneficial to reduce the mortality associated with this disease.

     

Sialyl Lewis-Xi antigen in patients with gynecologic tumors

Sialyl Lewis-Xi antigen was measured by sandwich radioimmunoassay in sera from patients with various gynecologic tumors: 27 uterine myomas, 117 cervical cancers, 46 endometrial cancers, 54 benign ovarian cysts, and 47 ovarian cancers. Among the patients with uterine malignancies, only a few cases showed serum sialyl Lewis-Xi antigen values in excess of the cutoff limit. On the other hand, among the patients with ovarian cancers, serum sialyl Lewis-Xi antigen was elevated significantly in the following order: clinical stage I (44%), stage II (50%), and stage III (62%). The antigen level also correlated with the effect of treatment. However, serum sialyl Lewis-Xi antigen was elevated in 9% of patients with benign ovarian cysts and in 1.4% of normal volunteers. The lack of tumor specificity of sialyl Lewis-Xi antigen limits its diagnostic value for gynecologic malignancies, but serial measurement of this antigen may be useful in evaluating therapy and monitoring patients.     

卵巢癌患者外周血T淋巴细胞核仁形成区嗜银蛋白的研究

目的 :研究卵巢癌患者外周血T淋巴细胞核仁形成区嗜银蛋白 (AgNORs)与卵巢癌的临床特点及生物学行为的关系。方法 :以卵巢癌患者 36例为研究组 ;以良性卵巢肿瘤患者 17例及健康妇女 2 0例为对照组。利用KL型肿瘤免疫图像分析系统计数T淋巴细胞核仁银染面积与细胞核面积比值 (integratedsquare ,IS)。结果 :卵巢浆液性腺癌、子宫内膜样腺癌、粘液性腺癌及未分化腺癌的IS均值分别为 9.31± 1.96 %、7.4 1± 0 .39%、7.98± 2 .95 %、6 .78± 0 .70 % ;高分化、中分化、低分化卵巢癌患者IS均值分别为 9.6 6±1.85 %、8.37± 1.95 %、8.16± 2 .0 5 % ;Ⅰ期、Ⅱ期、Ⅲ期及Ⅳ期卵巢癌患者的IS均值分别为 8.80± 1.35 %、10 .6 5± 0 .96 %、9.12± 1.6 3%、6 .0 1± 0 .4 5 % ;良性卵巢肿瘤及健康妇女的IS均值分别为 9.0 9± 1.83%、9.6 3± 1.5 2 %。不同组织学类型、不同分化级别卵巢癌患者其外周血T淋巴细胞AgNORs表达差异无显著性 (P >0 .0 5 )。Ⅳ期卵巢癌与Ⅰ、Ⅱ、Ⅲ期卵巢癌及对照组患者的外周血T淋巴细胞AgNORs表达有高度显著性差异 (P <0 .0 1)。结论 :Ⅳ期卵巢癌患者较Ⅰ、Ⅱ、Ⅲ期卵巢癌及对照组患者外周血T淋巴细胞rD NA转录活性及细胞免疫功能明显降低 ,这可能是导致卵巢癌进展的因素之一     

CA 15-3 as a tumor marker in gynecological malignancies

Serum levels of CA 15-3 were measured in 778 samples from 270 patients with benign and malignant gynecological conditions. Malignant tumors were present in 180 patients including 58 cases with cancer of the ovary, 47 of the endometrium, 61 of the cervix, and 14 of the vulva. The 90 cases with benign conditions included 24 patients with ovarian tumors, 28 with fibromyomatosis, 18 with endometriosis, and 20 with endometrial hyperplasia. Of 180 cancer patients, CA 15-3 serum levels were elevated (greater than 30 U/ml) in 74 cases (41%) and the frequency of abnormal marker values increased with clinical stage. Of 90 patients with benign conditions, high CA 15-3 levels were found in 5 cases (6%) with benign ovarian tumors. Elevated levels of the marker were most commonly seen in ovarian cancer patients (71%). In endometrial, cervical, and vulvar cancer abnormal CA 15-3 values occurred in 32, 26, and 14%, respectively. In endometrial cancer the percentage of positive marker levels increased with more infiltrating and/or less differentiated tumors. A positive correlation was found between residual tumor after surgery and CA 15-3 levels. Serial measurements in sera of patients who underwent chemotherapy showed a good correlation with response to treatment. CA 15-3 values were correlated with clinical course of disease in 87% of cases.