CA125 In Patients Research Articles

Serum Levels of CA19‐9 in patients with nonmalignant respiratory diseases

CA19-9 is a specific tumor marker in patients with gastrointestinal cancer; however, some patients with respiratory disease can have elevated serum levels of CA19-9 as well. In this study we evaluated serum CA19-9 levels of patients with nonmalignant respiratory diseases. We also estimated the prognostic significance of elevated serum levels of CA19-9 in patients with interstitial lung diseases. The study included 554 patients who had been diagnosed at our hospital during the period of 1984-2005. Serum CA19-9 levels in these patients were measured with a commercially available kit. Elevated levels (>37 U/mL) of CA19-9 were observed in 30.7% of patients with lung cancer. Furthermore, 38.9% of patients with idiopathic interstitial pneumonia (IIP), collagen disease-associated pulmonary fibrosis (CDPF), diffuse panbronchiolitis (DPB), and bronchiectasis had elevated serum CA19-9 levels. Survival rates were significantly lower in patients with interstitial lung diseases (IIP and CDPF) and elevated serum CA19-9 levels than in those with levels in the normal range (P=0.0065). Serum CA19-9 was elevated in some patients with nonmalignant diffuse lung diseases. Therefore, clinicians should pay attention to the evidence that increased serum CA19-9 levels can be found in nonmalignant respiratory disease patients. In patients with IIP and CDPF, elevated serum CA19-9 levels may be related to poor prognosis.

Prognostic Value of Preoperative Serum Levels of CEA and CA19-9 in Patients with Colorectal Cancer

Purpose: The significance of serum levels of CEA and CA19-9 in forming a prognosis for colorectal cancer patients remains as subject for debating. The aim of this study is to assess their correlations with tumor pathology and their prognostic values. Methods: We analysed the data on 274 patients with colorectal cancer who had been treated by resection from Jan. 1997 to Aug. 2005. Correlation of the preoperative serum values of CEA and CA19-9 with clinocopathologic features, including prognosis, of the patients was investigated. Results: The positivity rates of the two tumor markes were significantly correlated with tumor size, differentiation, TNM staging, venous invasion, and neural invasion. In addition, the positivity rate of CEA was related to lymphatic invasion and that of CA19-9 to gender. In the univariate analysis, CEA (P＜0.001), CA19-9 (P＜0.001), tumor size (P=0.011), TNM staging (P＜0.001), lymphatic invasion (P=0.003), venous invasion (P＜0.001), neural invasion (P＜0.001), and differentiation (P=0.023) correlated with survival of the patients. In the stepwise multivariate analysis, an advanced TNM stage (P＜0.001), positive venous invasion (P=0.011), and positive neural invasion (P=0.013) were independent prognostic factors for poor survival. Conclusions: Our results demonstrated that high serum levels of tumor markers were associated with more aggressive cancers, but in the multivariate analysis, CEA and CA19-9 were found not to be independent prognostic factors.

Circulating CA125 in Patients with Peritoneal Mesothelioma Treated with Cytoreductive Surgery and Intraperitoneal Hyperthermic Perfusion

Recent phase I/II trials report encouraging results in selected patients with peritoneal mesothelioma (PM) treated with cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). Circulating tumor markers have never been extensively investigated in the management of PM. We assessed the clinical role of markers in a large series of patients with PM undergoing CRS and IPHP. Clinical data on 60 patients with PM operated with the intention to perform adequate CRS (residual tumor nodules <or= 2.5mm) and IPHP were prospectively collected. Marker levels were determined pre-operatively, post-operatively, and routinely during long-term follow-up. Baseline diagnostic sensitivity, accuracy in monitoring response to treatment or tumor progression and prognostic significance were determined. Baseline diagnostic sensitivity was 53.3% for CA125, 0 for CEA, 3.8% for CA19.9 and 48.5% for CA15.3. Forty-six patients underwent adequate cytoreduction and IPHP; gross residual tumor was left after the operation in fourteen. Postoperatively, CA125 became negative in 21/22 patients with elevated baseline levels undergoing adequate CRS and IPHP, while remained elevated in 9/9 patients with persistent macroscopic disease. CA125 became positive in 12/12 patients with elevated baseline levels developing disease progression after adequate CRS and IPHP. Baseline CA125 showed borderline prognostic significance only among patients not previously treated with systemic chemotherapy. CA125 was elevated in the majority of patients with PM in the present series. Serial maker measurements paralleled tumor growth or regression after CRS and IPHP, suggesting the need of further studies to assess the role of CA125 in this clinical setting.

Citation classics in Fertility and Sterility, 1975–2004

Citation classics in Fertility and Sterility, 1975–2004

Utility of a novel serum tumor biomarker HE4 in patients with uterine cancer

5036 Background: Approximately 40,880 new cases of uterine cancer are diagnosed in the U.S. annually resulting in 7,310 deaths. Uterine cancer is surgically staged and 75% of patients present with stage I disease. Patients with stage I tumors with intermediate to high risk factors have a recurrence rate of 20 to 30%. Serum CA125 is elevated in 75% of patients with advanced stage disease and in only 17% of patients with early stage disease. The use of CA125 for the detection of recurrent disease is limited at best. Only 25% of patients with asymptomatic recurrent disease have an elevated CA125. A better marker indicating early recurrent disease is needed. The objective of this study was to examine the value of a novel serum tumor marker HE4 in endometrial cancer. Methods: Serum samples from two prospective IRB approved studies at two institutions were analyzed to compare HE4 with CA125 in patients who had surgical staging for uterine cancer. Normal controls were obtained from healthy patients. Informed consent was obtained from all patients and blood samples were drawn pre-operatively. HE4 and CA125 levels were determined using assays from Fujirebio Diagnostic Inc. ROC curves were constructed for each tumor marker and the sensitivity at a set specificity of 95% was determined. Results: Serum from 156 controls and 233 patients with surgically staged endometrial cancer; (151 stage I, 21 stage II, 47 stage III and 14 stage IV) were examined. The area under the ROC curves (ROC-AUC) for HE4 and CA125 were determined and compared ( Table1 ). At 95% specificity, the sensitivity for differentiation of controls versus all stages was 44.9% for HE4 compared to 25.2% for CA125 (p = 0.0001). For stage I cases, HE4 showed an improvement in the sensitivity of 20.5% compared to CA125 (37.1% vs 16.6%, p = 0.0001). Conclusions: HE4 is elevated in all stages of endometrial cancer and has a greater sensitivity for discrimination from normal controls compared to CA125. As well, HE4 is elevated in early stage endometrial cancer and should be investigated as a marker for early recurrent disease. [Table: see text] [Table: see text]

The levonorgestrel-releasing intrauterine device reduces CA-125 serum levels in patients with endometriosis

This study compared the long-term effects of the levonorgestrel-releasing intrauterine device with those of GnRH agonist administration on serum levels of CA-125 in patients with endometriosis. The levonorgestrel-releasing intrauterine device was found to be as efficient as GnRH agonist in reducing CA-125 serum levels.

Serum levels of KL‐6 are positively correlated with those of CA15‐3 in patients with interstitial pneumonia associated with collagen diseases

Wong et al. reported two patients with interstitial pneumonia (IP) associated with collagen diseases (dermatomyositis (DM) and polymyositis (PM)) who showed elevated levels of CA15-3 but did not have breast cancer.1 The authors did not measure the level of KL-6, because measurement of this parameter was available only in Japan in 2005. We examined the relationship between the serum levels of KL-6 (Picolumi® KL-6, Sanko Junyaku, Tokyo, Japan) and those of CA15-3 (Lumipulse® CA15-3, Fujirebio, Tokyo, Japan) in 20 female patients with IP associated with collagen diseases (rheumatoid arthritis (seven cases), PM (four), systemic sclerosis (three), Sjögren syndrome (three), mixed connective tissue disease (two) and DM (one)). The normal range of KL-6 and CA15-3 are <500 U/mL and ≤27.0 U/mL, respectively. As shown in Figure 1, there was a significantly positive correlation between the levels of KL-6 and those of CA15-3 (r = 0.74, P < 0.001). In five cases, the levels of CA15-3 were above the normal range, but none had a diagnosis of breast cancer by mammography. Relationship between the serum levels of KL-6 and those of CA15-3 in 20 patients with interstitial pneumonia associated with collagen diseases. A significantly positive correlation was noted by a linear regression analysis (r = 0.74, P < 0.001). KL-6 was initially identified as a tumour marker for adenocarcinoma of the lung. When the lung interstitium is injured, KL-6, which is mainly expressed on the surface of alveolar type II cells in the lung, fluxes into the blood circulation following an increase in the permeability of the damaged air–blood barrier.2 High serum levels of KL-6 are detected not only in patients with adenocarcinoma of the lung, pancreas or breast, but also in patients with IP including idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, radiation pneumonitis, pulmonary sarcoidosis, collagen diseases-associated IP and methotrexate-induced IP.2 KL-6 is now used in Japan as a serum marker for the purpose of making a diagnosis of IP, and monitoring its severity and therapeutic efficacy.3 CA15-3 is a marker for the early detection of a recurrence of breast cancer and for assessing the efficacy of treatment for metastatic breast cancer.4 This antigen is recognized by two monoclonal antibodies, namely 115D8 and DF3, which react against the human milk-fat globule membrane and breast cancer cells, respectively.5, 6 High serum levels of CA15-3 are detected not only in patients with breast cancer, but also in patients with adenocarcinoma of the lung, pancreas, kidney, ovary, uterus and colon.7 Both epitopes of KL-6 and CA15-3 exist in the different positions of Mucin-1 (MUC-1) expressed on the surface of various epithelial cells.8 MUC-1, classified as one of the mucin family, is a high-molecular-weight glycoprotein rich in O-glycosylated serine and threonine residues. The upregulated expression of MUC-1 has been noted in breast and lung adenocarcinomas.9 This might be the reason why the serum levels of KL-6 positively correlated with those of CA15-3. Ogawa et al. reported that the sensitivity of KL-6 was higher than that of CA15-3 in patients with relapsed breast cancer.10 According to the results of this study, the following points are important: (i) the levels of CA15-3 may increase not only in patients with adenocarcinoma including breast cancer but also those with IP; (ii) CA15-3 might thus be usable as a parameter of IP in patients without adenocarcinoma, including breast cancer.

CA125 in ovarian cancer: European Group on Tumor Markers guidelines for clinical use

CA125 is currently the most widely used tumor marker for ovarian epithelial cancer. The aim of this article is to provide guidelines for the routine clinical use of CA125 in patients with ovarian cancer. Due to lack of sensitivity for stage I disease and lack of specificity, CA125 is of little value in the detection of early ovarian cancer. At present, therefore, CA125, either alone or in combination with other modalities, cannot be recommended for screening for ovarian cancer in asymptomatic women outside the context of a randomized controlled trial. Preoperative levels in postmenopausal women, however, may aid the differentiation of benign and malignant pelvic masses. Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment. Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease, the clinical value of this lead-time is unclear. CA125 is the ovarian cancer marker against which new markers for this malignancy should be judged.

CA125 in ovarian cancer: European Group on Tumor Markers guidelines for clinical use

CA125 is currently the most widely used tumor marker for ovarian epithelial cancer. The aim of this article is to provide guidelines for the routine clinical use of CA125 in patients with ovarian cancer. Due to lack of sensitivity for stage I disease and lack of specificity, CA125 is of little value in the detection of early ovarian cancer. At present, therefore, CA125, either alone or in combination with other modalities, cannot be recommended for screening for ovarian cancer in asymptomatic women outside the context of a randomized controlled trial. Preoperative levels in postmenopausal women, however, may aid the differentiation of benign and malignant pelvic masses. Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment. Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease, the clinical value of this lead-time is unclear. CA125 is the ovarian cancer marker against which new markers for this malignancy should be judged.

Impact of Dominant Stenoses on the Serum Level of the Tumor Marker CA19-9 in Patients with Primary Sclerosing Cholangitis

Patients with primary sclerosing cholangitis (PSC) have an increased risk of developing hepatobiliary tumors. The tumor marker CA19-9 was claimed to indicate the occurrence of bile duct carcinoma. This study aimed to assess whether increased serum levels of CA19-9 in PSC patients with dominant stenoses indicate bile duct carcinoma. The study cohort comprised 106 patients treated over a median time of 5.0 years (range 0.5 - 13 years). All patients were treated with ursodeoxycholic acid (UDCA) and whenever they developed dominant stenoses by endoscopic dilatation of these stenoses. In endoscopically treated patients, CA19-9 levels were measured before and 3, 6, 12 and 24 months after endoscopic dilatation. Of the 106 patients, 22 carcinoma-free patients and 3 patients with bile duct carcinoma had elevated CA 19 - 9 levels. In 14 out of 25 patients with elevated CA19-9 levels, dominant stenoses were diagnosed and treated by endoscopic dilatation. In 71.4 % of the endoscopically treated patients, CA19-9 levels decreased following the endoscopic intervention. In PSC patients, increased serum levels of CA19-9 are rarely due to the development of bile duct carcinoma. In patients with dominant stenoses, the relief of biliary obstruction by endoscopic dilatation may lead to a decrease of the serum levels of CA19-9.

Serum tumor necrosis factor alpha receptors p55/p75 ratio and ovarian cancer detection

Objective Early ovarian cancer detection is still very difficult and patients are mostly in advanced stages, with obvious influence on poor prognosis. Method Fifty-one ovarian cancer patients and 16 healthy controls had the serum concentrations of TNFα receptor p55, p75 and CA-125 measured prospectively and preoperatively. Result Mean concentrations of TNFα receptor p55, p75 and CA-125 in patients with ovarian cancer were higher than in controls. The ratios of p55 and p75 receptor in ovarian cancer and controls were 0.73±0.38 and 0.55±0.06 respectively. The areas under ROC curve in detecting malignancy (all FIGO stages) were 0.73, 0.65, 0.88 and 0.85 for p55, p75, p55/p75 ratio and CA-125 respectively. The areas under ROC curve in detecting stage I of ovarian cancer were 0.52, 0.60, 0.84 and 0.66 for p55, p75, p55/p75 ratio and CA-125 respectively. Conclusion Serum TNFα p55/p75 ratio showed promising value in ovarian cancer detection.

Clinical value of serum tumor supplied group of factor in diagnosis of epithelial ovarian cancer

Objective: To evaluate the clinical value of serum tumor supplied group of factor (TSGF) in diagnosis of epithelial ovarian cancer. Methods: The serum TSGF was tested in 69 patients with epithelial ovarian cancer, 28 patients with benign ovarian lesion and 61 healthy women. The serum levels of vascular endothelial growth factor (VEGF) and CA125 were determined in patients with epithelial ovarian cancer and in those with benign ovarian lesion. The correlations of TSGF with VEGF and CA125 were investigated. Results: The serum level of TSGF in patients with epithelial ovarian cancer was obviously higher than in patients with benign ovarian lesion and in healthy women (P 0.05). The serum level of TSGF and VEGF and CA125 in patients with epithelial ovarian cancer showed positive correlation (P<0.01, P<0.05, respectively). Conclusion: There is no marked difference in diagnostic value among TSGF, VEGF and CA125. TSGF has a certain value in diagnosis of epithelial ovarian cancer, and is helpful to distinguish epithelial ovarian cancer from benign ovarian lesion.

The effect of ascites, mass volume, and peritoneal carcinomatosis on serum CA125 levels in patients with ovarian carcinoma

The aim of this study is to investigate the effects of ascites, ovarian mass volume, and peritoneal carcinomatosis on serum CA125 levels in patients with nonmucinous epithelial ovarian carcinoma. Serum CA125 levels were determined by a commercial enzyme immunoassay kit in a series of 98 patients with stage I-IV nonmucinous epithelial ovarian carcinoma. Amounts of ascites were determined in each patient with ascites. Ovarian mass volumes were calculated in 22 patients with stage I disease without ascites. Peritoneal carcinomatosis was detected in 35 ovarian cancer patients. Serum CA125 levels were compared among the patients with different clinical conditions.Serum CA125 levels were significantly higher in cases of ovarian cancer with ascites when compared with those without ascites (P &lt; 0.01). Abnormal levels of serum CA125 were found in 80% of all patients; these abnormal levels were detected in 92% and 97% of the patients with ascites and with peritoneal carcinomatosis, respectively. A positive correlation between serum CA125 levels and ascites amounts was found in patients with ascites (P &lt; 0.01, r = 0.74). However, there was no correlation between ovarian mass volumes and levels of serum CA125 in patients having stage I disease but no ascites (P = 0.5, r = 0.15). Our results showed that serum CA125 levels might be affected by the amount of ascites and the presence of peritoneal carcinomatosis but not with ovarian mass volume. However, these findings need to be confirmed in more and larger studies. These results may be beneficial in the management of ovarian carcinoma patients with elevated CA125 levels.

The Prognostic Value of Pretherapeutic Tetranectin and CA-125 in Patients with Relapse of Ovarian Cancer

Objective. The aim of the study was to examine the prognostic values of, respectively, tetranectin (TN) and CA-125 measured in serum from patients presenting with relapse of ovarian cancer (OC).Methods. TN and CA-125 were measured in serum samples from 75 patients with relapse of OC before the start of second-line chemotherapy. The endpoint used was death of OC. The variables were analyzed by univariate life table analysis and multivariate Cox analysis.Results. A significantly shortened survival was found for patients with low serum TN values compared to patients with serum TN levels above one of the cutoff levels. The survivals are illustrated by life tables. No prognostic function was found for CA-125. TN and relapse ≤12 months after primary treatment were the only significant independent prognostic variables among the following variables tested in the Cox analyses: primary and second-line treatment, CA-125, age, histology, performance score, tumor localization, and size.Conclusion. Serum TN determination may be valuable in the selection of patients with relapse of OC for new treatment strategies in future studies.

Predictive values of serum tumour markers tetranectin, OVX1, CASA and CA125 in patients with a pelvic mass

Our objective was to compare the predictive value of the well-established tumour marker CA125 with the newer tumour markers tetranectin (TN), OVX1 and CASA in distinguishing benign and malignant pelvic masses in women. Participants included 185 women, 19 years or older, with a pelvic mass planned for surgical exploration. Significantly different CA125 levels were found between benign tumours and localised ovarian cancer (OC), advanced OC and other non-OCs. Significantly different TN levels were found between benign tumours and advanced OC (stage III/IV), between benign tumours and other cancers and between all OCs and other cancers. For CASA, significant differences were found between benign tumours and all OCs as well as advanced OC. No significant differences could be demonstrated for OVX1. Significant correlations for the 44 OC patients were found between CA125, TN and CASA. No significant correlations were found for OVX1, possibly because of the method used for collection and handling of serum samples. None of the new markers had any additional predictive value compared to CA125. TN and CASA levels correlated with FIGO stage and could be used to discriminate between benign and advanced OC. However, in comparison to the performance of CA125, the additional discriminative value of TN and CASA was minor. Int. J. Cancer 89:519–523, 2000. © 2000 Wiley-Liss, Inc.

Predictive values of serum tumour markers tetranectin, OVX1, CASA and CA125 in patients with a pelvic mass

Our objective was to compare the predictive value of the well-established tumour marker CA125 with the newer tumour markers tetranectin (TN), OVX1 and CASA in distinguishing benign and malignant pelvic masses in women. Participants included 185 women, 19 years or older, with a pelvic mass planned for surgical exploration. Significantly different CA125 levels were found between benign tumours and localised ovarian cancer (OC), advanced OC and other non-OCs. Significantly different TN levels were found between benign tumours and advanced OC (stage III/IV), between benign tumours and other cancers and between all OCs and other cancers. For CASA, significant differences were found between benign tumours and all OCs as well as advanced OC. No significant differences could be demonstrated for OVX1. Significant correlations for the 44 OC patients were found between CA125, TN and CASA. No significant correlations were found for OVX1, possibly because of the method used for collection and handling of serum samples. None of the new markers had any additional predictive value compared to CA125. TN and CASA levels correlated with FIGO stage and could be used to discriminate between benign and advanced OC. However, in comparison to the performance of CA125, the additional discriminative value of TN and CASA was minor.

Effect of Topotecan on Serum CA-125 in Patients with Advanced Epithelial Ovarian Cancer

The effect of topotecan on CA-125 serum levels was evaluated in 30 patients with advanced epithelial ovarian cancer. All patients had progressive disease and were relapsing during (11 patients) or after (19 patients) chemotherapy containing paclitaxel and platinum. Topotecan (1.0 mg/m2/day) was administered intravenously on Days 1–5 every 3 weeks. The patients had received a median of 2 (1–5) prior regimens. Four patients had increased CA-125 only, and 26 had both measurable disease and increased CA-125. Two patients (7%) achieved a clinical partial response with durations of 5 and 10+ months, respectively. Eighteen other patients (60%) exhibited no clinical change with a median duration of 5+ months (range: 2–11+ months). Among these patients 9 (30%) had a biochemical response. The rate of change in CA-125 (s, slope of the exponential regression curve) during treatment with topotecan was compared with s over a period before treatment. A decrease in s was observed in 20 patients (74%). Comparing the mean values of s before and during topotecan, a significant (P = 0.005) decrease was seen in the CA-125 serum levels. The mean doubling times before and during treatment were 59 and 1421 days, respectively. Toxicity was mainly hematologic. Neutropenia grades III and IV were seen in 16 and 10 patients, respectively. No patients died due to side effects. Generally the side effects were mild to moderate. In conclusion, at the given dose intensity topotecan shows activity in advanced paclitaxel- and platinum-resistant ovarian cancer based on CA-125 measurements.

Predictive values of serum tumour markers tetranectin, OVX1, CASA and CA125 in patients with a pelvic mass

Predictive values of serum tumour markers tetranectin, OVX1, CASA and CA125 in patients with a pelvic mass

Usefulness of the epithelial tumor marker CA-125 in non-Hodgkin's lymphoma.

CA-125, a commonly used tumor marker for epithelial ovarian cancer, is a glycoprotein found in normal tissues derived from coelomic epithelia. Increased serum levels of CA-125 have also been found in nongynecologic tumors and nonmalignant diseases involving the peritoneum. A few recent studies and sporadic case reports have reported increased CA-125 levels in patients with non-Hodgkin's lymphoma (NHL). In our study, we aimed to evaluate the serum levels of CA-125 in patients with NHL and determine its potential role to show disease activity in NHL. Serum levels of CA-125 were measured in 61 patients with NHL and were found to be correlated with clinical stage, site of involvement, and disease activity.

Effect of Low-Dose Oral Etoposide on Serum CA-125 in Patients with Advanced Epithelial Ovarian Cancer

The effect of oral etoposide on CA-125 serum levels was evaluated in 17 patients with epithelial ovarian cancer and progressive disease during, or relapsing after, prior chemotherapy. Only three patients had measurable lesions at extraperitoneal sites. Five had no measurable lesions. The oral etoposide dose was 50 mg b.d. for 7 days every 3 weeks, escalating to 10 or 14 days and continued until clinical progression. CA-125 after 4 courses was compared to baseline (CA-125 ratio). The rate of change of CA-125 (s,slope of the exponential regression curve) during the first 4 courses was compared tosover a similar period before treatment. One patient had a clinical partial response. Two other patients had a biochemical response (CA-125 ratio <0.5). Although the biochemical response rate was modest (12.5%), a decrease ofswas observed in 14/16 patients (P= 0.02). The mean change ofsrepresented an increase of mean doubling time from 52 to 693 days. No patients were withdrawn because of toxicity. General malaise, nausea, diarrhea, and anemia were the most important side effects. At the given dose schedule, oral etoposide shows activity in advanced ovarian cancer if the rate of change of CA-125 is used as a measure of activity.