Cancer-associated Serum Antigen Research Articles

Breast cancer humoral immune response: involvement of Lewis y through the detection of circulating immune complexes and association with Mucin 1 (MUC1)

BackgroundIn cancer patients, MUC1 glycoprotein may carry Lewis y which could be involved in immune response. Purposes: 1- to evaluate the presence of Lewis y and MUC1 in circulating immune complexes (Lewis y/CIC and MUC1/CIC, respectively) and their correlation; 2- to analyze the possible presence of Lewis y in carbohydrate chains of tumoral MUC1 glycoprotein and 3- to correlate serum and tissue parameters considered.MethodsPretreatment serum and tissue breast samples from 76 adenocarcinoma, 34 benign and 36 normal specimens were analyzed. Anti-MUC1 and anti-Lewis y MAbs were employed. To detect Lewis y/CIC and MUC1/CIC, ELISA tests were developed; serum samples containing MUC1 were previously selected by Cancer Associated Serum Antigen (CASA). Immunoprecipitation (IP) was performed in 9 malignant, benign and normal samples and analyzed by SDS-PAGE and Western blot. Lewis y and MUC1 expression was studied by immunohistochemistry (IHC). Statistical analysis was performed employing principal component analysis (PCA), ANOVA, Tukey HSD, Chi square test and classical correlation (p < 0.05).ResultsBy ELISA, Lewis y/IgM/CIC levels showed statistically significant differences between breast cancer versus benign and normal samples; mean ± SD values expressed in OD units were: 0.525 ± 0.304; 0.968 ± 0.482 and 0.928 ± 0.447, for breast cancer, benign disease and normal samples, respectively, p < 0.05. Lewis y/IgG/CIC did not show any statistically significant difference. MUC1/IgM/CIC correlated with Lewis y/IgM/CIC. By CASA, 9 samples with MUC1 values above the cut off were selected and IP was performed, followed by SDS-PAGE and Western blot; bands at 200 kDa were obtained with each MAb in all the samples. By IHC, with C14 MAb, 47.5%, 31% and 35% of malignant, benign and normal samples, respectively, showed positive reaction while all the samples were positive with anti-MUC1 MAb; in both cases, with a different pattern of expression between malignant and non malignant samples.ConclusionOur findings support that in breast cancer there was a limited humoral immune response through Lewis y/IgM/CIC levels detection which correlated with MUC1/IgM/CIC. We also found that Lewis y might be part of circulating MUC1 glycoform structure and also that Lewis y/CIC did not correlate with Lewis y expression.

Pre-Treatment Prediction of Chemoresistance in Second-Line Chemotherapy of Ovarian Carcinoma: Value of Serological Tumor Marker Determination (Tetranectin, YKL-40, CASA, CA 125)

To examine if the determination of the levels of serological tumor markers at time of relapse had any predictive value for chemoresistance in the second-line treatment of ovarian cancer patients. From a registry of consecutive single-institution patients with epithelial ovarian carcinoma pretreated with paclitaxel plus platinum, we selected 82 patients with (a) solid tumor recurrence, and (b) second-line chemotherapy consisting of topotecan (platinum-resistant disease) or paclitaxel plus carboplatin (platinum-sensitive disease). Stored serum samples were analyzed for the biochemical tumor markers tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The serum tumor marker levels at time of relapse were correlated with response status at landmark time after 4 cycles of second-line chemotherapy. Univariate and multivariate logistic regression analyses (chemoresistant vs non-chemoresistant disease) were performed. At landmark time, 26% of patients had progression according to the GCIG (Gynecologic Cancer Intergroup) progression criteria. In univariate logistic regression analysis, the tumor markers tetranectin (OR 0.4; 95% CI: 0.2-0.8; p=0.008), YKL-40 (OR 1.8; 95% CI: 1.0-3.3; p=0.045), and CASA (OR 1.8; 95% CI: 1.2-2.7; p=0.007) had predictive value for second-line chemoresistance, whereas serum CA 125 had no predictive value. In a multivariate logistic regression analysis, serum tetranectin and CASA both had independent predictive value for chemoresistance. The combined determination of tetranectin and CASA had a specificity of 90% with 33% sensitivity for the prediction of chemoresistance (area under the receiver operating characteristic curve = 0.78; 95% CI: 0.66-0.91; p=0.001). Low serum levels of tetranectin, or high serum levels of CASA or YKL-40, are associated with increased risk of second-line chemoresistance in patients with ovarian cancer.

Pre-treatment prediction of chemoresistance in second-line chemotherapy of ovarian carcinoma: value of serological tumor marker determination (tetranectin, YKL-40, CASA, CA 125)

To examine if the determination of the levels of serological tumor markers at time of relapse had any predictive value for chemoresistance in the second-line treatment of ovarian cancer patients. From a registry of consecutive single-institution patients with epithelial ovarian carcinoma pretreated with paclitaxel plus platinum, we selected 82 patients with (a) solid tumor recurrence, and (b) second-line chemotherapy consisting of topotecan (platinum-resistant disease) or paclitaxel plus carboplatin (platinum-sensitive disease). Stored serum samples were analyzed for the biochemical tumor markers tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The serum tumor marker levels at time of relapse were correlated with response status at landmark time after 4 cycles of second-line chemotherapy. Univariate and multivariate logistic regression analyses (chemoresistant vs non-chemoresistant disease) were performed. At landmark time, 26% of patients had progression according to the GCIG (Gynecologic Cancer Intergroup) progression criteria. In univariate logistic regression analysis, the tumor markers tetranectin (OR 0.4; 95% CI: 0.2-0.8; p=0.008), YKL-40 (OR 1.8; 95% CI: 1.0-3.3; p=0.045), and CASA (OR 1.8; 95% CI: 1.2-2.7; p=0.007) had predictive value for second-line chemoresistance, whereas serum CA 125 had no predictive value. In a multivariate logistic regression analysis, serum tetranectin and CASA both had independent predictive value for chemoresistance. The combined determination of tetranectin and CASA had a specificity of 90% with 33% sensitivity for the prediction of chemoresistance (area under the receiver operating characteristic curve = 0.78; 95% CI: 0.66-0.91; p=0.001). Low serum levels of tetranectin, or high serum levels of CASA or YKL-40, are associated with increased risk of second-line chemoresistance in patients with ovarian cancer.

Cancer-associated serum antigen level: a novel prognostic indicator for survival in patients with recurrent ovarian carcinoma

Cancer-associated serum antigen level: a novel prognostic indicator for survival in patients with recurrent ovarian carcinoma

Cancer-associated serum antigen level: a novel prognostic indicator for survival in patients with recurrent ovarian carcinoma

The aim was to examine the value of the pretherapeutic serum cancer-associated serum antigen (CASA) level as a prognostic factor for survival in patients with recurrent epithelial ovarian carcinoma. Serum levels of CASA and cancer antigen (CA)125 were prospectively determined in 70 consecutive patients with recurrent ovarian cancer before the start of second-line chemotherapy. Univariate and multivariate analyses of survival were performed. The median level of serum CASA was 6.5 U/mL (range: 0.2-1437 U/mL). Univariate analysis showed that patients with a CASA level >10.0 U/mL had significantly shorter survival than patients with CASA level < or =10.0 U/mL (P= 0.002). Using different CASA cutoff levels (6.0, 6.5, and 10.0 U/mL), multivariate Cox analyses identified CASA as an independent prognostic factor for survival at every cutoff level. The strongest prognostic function for CASA was found at a cutoff level of 10.0 U/mL (>10 vs < or =10 U/mL; hazard ratio, 2.7; 95% confidence interval, 1.6-4.7; P < 0.001). The pretreatment CA125 level was not found to be significantly associated with survival by any of the cutoffs (35, 65, 132, and 339 U/mL). A pretreatment elevated level of the tumor marker CASA is an adverse prognostic factor for survival in patients with ovarian cancer relapse.

Transient Elevation of the Tumor Markers CA 15-3 and CASA as Markers of Interstitial Lung Disease Rather than Underlying Malignancy in Dermatomyositis Sine Myositis

A 37-year-old woman with severe interstitial lung disease associated with dermatomyositis sine myositis is reported. A thoracoscopic lung biopsy revealed organizing diffuse alveolar damage. Significantly elevated serum levels of the tumor markers CA 15-3 and CASA (cancer-associated serum antigen) were detected, but no evidence of an underlying malignancy (including breast and ovarian) was found on serial clinical and radiologic examinations. These levels gradually normalized as the interstitial lung disease responded to a combination of cyclophosphamide and corticosteroids. The use of the CA 15-3 and CASA assays to measure serum levels of the highly glycosylated, high-molecular-weight mucin MUC1 in interstitial lung disease has not been previously described. Clinicians should therefore be aware that elevation of these tumor markers may reflect the presence of interstitial lung disease rather than an underlying malignancy in patients with dermatomyositis, especially if the levels normalize after successful treatment of the lung disease.

Évaluation clinique du cancer associated serum antigen (CASA) comme marqueur tumoral des cancers ovariens : comparaison avec le CA 125

Clinical evaluation of cancer associated serum antigen (CASA) as a serum marker in ovarian cancer : comparison with CA 125. The aim of this retrospective study is to evaluate the interest of the cancer associated serum antigen (CASA), for the management of patients with ovarian cancer. The study concerns a population of 31 patients of median age 62 years (38 – 79). Cut-off values of 35 kU/L and 4 kU/L for respectively CA125 and CASA were used. The sensitivity of the preoperative level of CASA is 57 %. After surgery, only the positivity of post-operative CASA level is correlated to residual disease (p = 0,0020). The lowest level of CASA (cut-off = 2 kU/L) is a prognostic index for disease free survival, independently of the apparent half-life of CA 125. The combination of CASA and CA 125 prior the second-look surgery increases the sensitivity of residual tumor detection by 18,2 % with respect to the use of CA 125 alone. The sensitivity of recurrent tumor detection is also increased with the combined use of these 2 markers. In conclusion, the combination of CASA and CA 125 optimises the biological monitoring of patients with ovarian cancer.

Assessment of bone response to systemic therapy in an EORTC trial: preliminary experience with the use of collagen cross-link excretion. European Organization for Research and Treatment of Cancer.

This study was designed to evaluate new bone resorption and tumour markers as possible alternatives to serial plain radiographs for the assessment of response to treatment. Thirty-seven patients with newly diagnosed bone metastases from breast cancer, randomized to receive oral pamidronate or placebo tablets in addition to anticancer treatment within the context of a multicentre EORTC trial, who were both assessable for radiographic response in bone and had serum and urine samples collected for more than 1 month were studied. The markers of bone metabolism measured included urinary calcium (uCa), hydroxyproline (hyp), the N-telopeptide cross-links of type I collagen (NTx) and total alkaline phosphatase. The tumour markers measured were CA15-3 and cancer-associated serum antigen (CASA). Before treatment, levels of Ntx, uCa and Hyp were elevated in 41%, 24% and 28% respectively, and CA15-3 and CASA increased in 69% and 50%. For assessment of response and identification of progression, Ntx was the most useful bone marker. All markers behaved similarly in no change (NC) and partial response (PR) patients. There was a significant difference (P ≤ 0.05) in Ntx levels (compared to baseline) at 1 and 4 months and in CA15-3/CASA at 4 months between patients with PR or NC and those with progressive disease (PD), and at 4 months between those with time to progression (TP) > 7 and those with TP ≤ 7 months. The diagnostic efficiency (DE) for prediction of PD following a > 50% increase in Ntx or CA15-3 was 78% and 62% respectively. An algorithm to predict response to therapy has been developed for future prospective evaluation. © 1999 Cancer Research Campaign

Differential diagnosis of peri- and postmenopausal ovarian cysts

Objectives: To test the value of preoperative and intracystic parameters in the differential diagnosis of ovarian cysts. Methods: Criteria for admisson of 58 patients were age >47 years, complete history, detection of CA 125 serum level, and ultrasound findings. Tumor markers (CA 125, cancer-associated serum antigen (CASA), CA 72-4), hormones (estradiol (E 2), follicle-stimulating hormone (FSH), luteinizing hormone (LH)), epidermal growth factor (EGF) receptor and c- erbB-2 amplification rate were detected in cyst fluid. Results: Of the 58 subjects, 9 (15.4%) had functional cysts, 37 (63.8%) had benign tumors and 12 (20.8%) had malignant tumors. No functional ovarian cyst presented as echoic or multilocular cyst sonographically. The serum CA 125 values demonstrated significant differences between the non-malignant and malignant patient groups ( P<0.0005). The majority (63.8%, n=37) of ovarian cysts were obtained at laparotomy, whereas only 36.2% ( n=21) were laparoscopically operated. The cyst fluid levels of FSH ( P<0.005) and LH ( P<0.05) were significantly lower in the functional group than in the benign or malignant group. Malignant cysts were significantly different from non-malignant cysts regarding low E 2 ( P<0.01), high FSH ( P<0.05) and CASA ( P<0.02) values. There were no significant correlations between EGF receptor ( P=0.14) and c- erbB-2 ( P=0.06) gene amplification rates and malignant histology. Conclusions: Simple ovarian cysts combined with normal serum CA 125 levels are candidates for conservative follow-up or laparoscopy. The serum CA 125 is a powerful marker for prediction of histology in postmenopausal ovarian cyst. Laparoscopic surgery may be considered in patients with multilocular sonographic findings and normal CA 125 serum level. Combining serum CA 125 levels with cyst fluid parameters (E 2, FSH, CASA) improves the sensitivity and specificity in predicting malignancy.

Cancer associated serum antigen (CASA) levels in patients with breast carcinoma and in 3 control groups without breast cancer.

We have examined the predictive value of measurements of CASA (Cancer Associated Serum Antigen) levels in patients with breast carcinoma. The measurement uses monoclonal antibodies that bind to an epitope on the polymorphic epithelial mucin. CASA levels were of less value compared with the levels of other tumor markers (CA 15-3, CA 549 and CEA) in the management of patients with early breast cancer.

Can manipulation of a pelvic tumour influence the serum level of cancer antigen 125 and cancer-associated serum antigen?

Cancer antigen 125 (CA 125) and cancer-associated serum antigen (CASA) were measured in 24 women with pelvic masses before and after a gynaecological examination and ultrasonography. CA 125 decreased median 16% after manipulation (P < 0.0001) and CASA decreased median 8% (P = 0.0077). The decline was found in patients with benign tumours as well as in patients with malignant tumours.

Serum mucin antigen (CASA) as a marker of amiodarone-induced pulmonary toxicity.

Amiodarone is used to treat life-threatening cardiac arrhythmias. Amiodarone-induced pulmonary toxicity (APT) can be difficult to diagnose. APT may result in increased mucus production and mucin expression. Thus, serum mucin-1 was evaluated as a marker for amiodarone-induced pulmonary toxicity. Concentrations of mucin-1 in peripheral blood were determined using cancer-associated serum antigen (CASA) assay in patients taking amiodarone. Eight of ten patients who developed major amiodarone toxicity had high serum CASA levels. Patients with toxicity had a significantly higher mean rank CASA concentration compared with those without major toxicity. CASA shows potential as a marker for amiodarone-induced toxicity, particularly pulmonary toxicity.

Serum concentrations of cancer antigen 125, placental alkaline phosphatase, cancer-associated serum antigen and free beta human chorionic gonadotrophin as prognostic markers for epithelial ovarian cancer.

To investigate the prognostic significance of elevated levels of cancer antigen 125 (CA125), placental alkaline phosphatase (PLAP), free beta human chorionic gonadotrophin (hCG) and cancer-associated serum antigen (CASA) in women with primary epithelial ovarian carcinoma. A two year follow up study of survival. A tertiary care gynaecological oncology unit. One hundred and eleven women with histologically confirmed epithelial ovarian cancer. Survival over a two year period. Stage corrected log-rank chi 2 tests demonstrated a significant effect on survival for all four tumour markers (CA125 P = 0.0142; PLAP P < 0.0001; CASA P = 0.0098; hCG P = 0.0002). This was confirmed when each variable was fitted together with disease stage in Cox proportional hazard models. When fitted as multiple variables in a Cox proportional hazard model, the addition of free beta-hCG and CASA to disease stage, PLAP concentrations and CA125 levels did not demonstrate further prognostic value. Levels of all four markers correlate with survival in patients with epithelial ovarian cancer. The combination of PLAP and CA125 concentrations together with disease stage may be used to predict survival but the addition of hCG and CASA levels do not give additional prognostic information.

The clinical value of tumour markers in the management of ovarian cancer.

It is now clear that the correct use of tumour markers in patients with epithelial ovarian carcinoma can make an impact on clinical management. Those of greatest current interest are CA 125, tissue polypeptide specific antigen, tumour-associated trypsin inhibitor and the mucins cancer-associated serum antigen and DVXl. Their value in screening is unproven and cannot be recommended outside clinical trials. They are all too non-specific for use in the diagnosis of ovarian carcinoma but when used with ultrasound can help in the differential diagnosis of a pelvic mass. Although elevated CA 125 concentrations prior to the third course of chemotherapy is the best indicator of poor prognosis, this information is not accurate enough to justify a change in therapy. The major role of CA 125 is in monitoring response to therapy. A precise definition of tumour response based on a 50% or 75% fall in serial CA 125 concentrations that is maintained for 1 month is as accurate as serial measurements of tumour size for determining whether a particular treatment is active. The role of regular CA 125 measurements during follow up is unclear. However, if there is suspicion of relapse and it is found that the CA 125 concentration has risen to over twice the upper limit of normal, the probability of relapse is so high as to make other investigations unnecessary. Patients with cancer of the ovary typically present with non-specific symptoms and advanced disease. Such cancer usually metastasizes as peritoneal deposits which are rarely palpable or detectable on scans. Tumour markers, therefore, have a greater potential value in the management of ovarian cancer than in virtually any other cancer type except choriocarcinoma.

A study of serum CASA and CA 125 levels in patients with ovarian carcinoma.

The assays of Cancer Associated Serum Antigen (CASA) and CA 125 were assessed in the management of patients with ovarian cancer. It was shown that CASA is sensitive to ovarian carcinoma, and both CASA and CA 125 are more useful when used in conjunction.

Are CASA and CA125 concentrations in peripheral blood sourced from peritoneal fluid in women with pelvic masses?

The Cancer associated serum antigen (CASA) and CA125 assays used in the management of ovarian cancer measure distinct high molecular weight glycoproteins. The mechanisms of secretion of these molecules into the peripheral circulation are not clearly understood. Concentrations of CASA and CA125 were assessed in peripheral blood, blood from veins draining ovarian and omental tumors, and peritoneal fluid in 20 women with pelvic masses. There was a near perfect correlation between peripheral vein and ovarian vein concentrations for both markers; concentrations in omental veins were higher than in peripheral veins in only a small proportion of cases, whereas the concentration in peritoneal fluid was universally much higher than in blood. These studies suggest a similar route of entry into the peripheral circulation and a similar half-life for these glycoproteins. These data provide no support for the hypothesis that a significant contribution to CA125 concentrations comes from peritoneal release by mesothelial cells rather than tumor cells, because the relative CA125 concentrations between compartments were similar to those of CASA within patients. The lack of a gradient between CASA levels in peripheral blood and tumor draining veins suggests that the CASA half-life is much longer than that predicted in animal studies. CA125 and CASA in peripheral blood are probably derived from markers secreted into peritoneal fluid and lymph, rather than directly into the bloodstream.

Mucin 1 antigens in the serum and bronchial lavage fluid of patients with lung cancer.

Lung cancer (LC) is the most common fatal malignancy, but there are no useful tumor markers for diagnosis or monitoring. Mucin 1 has an established role as a marker in other malignancies, but has undergone limited assessment in LC. Serum from 86 patients with LC and 24 with benign pulmonary disease (BPD), and bronchial lavage fluid from 55 LC patients and 21 BPD patients were tested using the Mucin 1 assays mammary serum antigen (MSA) and cancer-associated serum antigen (CASA). For LC, serum CASA achieved sensitivity of 57%, specificity of 93% relative to normals, and 63% specificity relative to BPD. For MSA the same parameters were 19%, 95%, and 92%. Serum CASA levels were significantly higher in LC patients compared with BPD (P = 0.024) but there was no difference for MSA (P = 0.635). CASA showed excellent correlation with tumor stage and in patients with changing status of disease, while MSA did not. By contrast there was no difference in bronchial lavage fluid tumor marker levels from LC and BPD patients (CASA, P = 0.87; MSA, P = 0.89). In a small series serum CASA appears to be a useful agent in detecting LC because it is elevated in all types and stages of LC, and its level correlates with stage and progress of disease. Some patients with BPD have elevated levels suggesting a greater value for monitoring rather than diagnosis. Both serum MSA testing and measurements of either marker in bronchial lavage fluid are of no value.

The management of ovarian carcinoma is improved by the use of cancer-associated serum antigen and CA 125 assays.

The new tumor-associated mucin assay, cancer-associated serum antigen (CASA), was assessed with the CA 125 assay for use in the management of patients with epithelial ovarian cancer. CASA and CA 125 were assessed retrospectively for use in (1) monitoring 28 patients with Stage 3 or 4 ovarian carcinoma during therapy, (2) predicting the outcome of 41 second-look laparotomies (SLL), and (3) predicting the survival outcome by measuring these levels after surgery but before chemotherapy in 65 patients with Stage 3 disease. Of 20 patients with recurrence after an initial response, the presence of CASA levels detected recurrence in 65% before clinical detection; CA 125, 50%; and the combination of CASA and CA 125, 80%. Six patients whose disease was in long-term remission did not have elevations of either marker. When used to predict the results of SLL, the positive predictive values of CASA and CA 125 were 77% and 100%, respectively. The negative predictive values for CASA and CA 125 were 71% and 66%, respectively. CASA detected 50% of positive SLL where microscopic disease only was found; the CA 125 test did not. Multivariate analysis of survival rates using levels of CASA and CA 125, age, residual disease, tumor type and grade, or the presence or absence of cisplatin in the chemotherapeutic regimen found that postoperative CASA levels ranked above all prognostic factors except age. CASA levels may be more accurate than surgical reporting of residual disease or they may define a subset of patients with biologically more aggressive ovarian carcinoma. The CASA test is sensitive to ovarian carcinoma, and both CASA and CA 125 are more useful when used in conjunction.

Evaluation of two new assays for tumor-associated antigens, CASA and OSA, found in the serum of patients with epithelial ovarian carcinoma—Comparison with CA125

Two new assays have been developed to measure tumor-associated antigens designated ovarian serum antigen (OSA) and cancer-associated serum antigen (CASA). Both assays are dual epitope ELISAs using the same capture monoclonal antibody (BC2); the second antibodies in the OSA and CASA assays are OM-1 and BC3, respectively. Using arbitrary cutoffs of 2.5 and 3.0 units/ml, 82 and 76% of 80 serum samples from ovarian cancer patients were positive for OSA and CASA, respectively, compared with 5 and 2.5% of samples from a control population of 40 women. A strong correlation was found between the two assays ( r = 0.80, P < 0.001). CA125 levels were obtained from 49 of the 80 samples; 82% of these samples were positive for CA125 (>35 U/ml), 82% for OSA and 73% for CASA. Of the 9 samples negative for CA125, 3 were positive for OSA and 3 were positive for CASA. Serum OSA, CASA, and CA125 levels were determined in serial samples from 20 ovarian carcinoma patients throughout the course of their treatment. Clinical course was accurately reflected by CA125 levels in 85% of patients, by CASA in 65%, and by OSA in 75%. In 4 patients, a rise in CASA levels and, in 2 patients, a rise in OSA levels significantly predated rising CA125 levels to predict recurrence. Six of 7 serum samples obtained prior to positive second-look laparotomy were negative for CA125, while 4 were positive for OSA and 6 were positive for CASA. These results indicate that the OSA and CASA assays could be superior to CA125 for detection of small volume occult ovarian carcinoma.