Normal Cancer Antigen 125 Levels Research Articles

Association of Cancer Antigen 125 with Long-Term Prognosis in Light-Chain Cardiorenal Amyloidosis

Introduction: Light-chain (AL) cardiorenal amyloidosis has been characterized as type 5 cardiorenal syndrome with fluid overload and poor prognosis. Cancer antigen 125 (CA125) has the potential for its use in evaluating fluid load and prognosis for heart failure. However, less details for CA125 in AL cardiorenal amyloidosis have been reported. Methods: Sixty patients diagnosed with AL cardiorenal amyloidosis were enrolled in this retrospective study. Patients were divided into two groups according to the cutoff point of CA125 level (35 U/mL). Logistic regression was used to screen variables associated with CA125. Cox regression analyses were utilized to verify the prognostic potential of CA125. Results: The mean age was 61 ± 8 years, and 68% of the participants were male. Compared to patients with normal CA125 levels (≤35 U/mL), patients with high levels of CA125 (>35 U/mL) had a higher proportion of New York Heart Association class >II, pericardial effusion, and edema, as well as a lower level of albumin and left ventricular longitudinal strain (LVLS). Logistic regression showed age, albumin, and LVLS to be independently associated with CA125. Seventeen (28%) patients died during the follow-up. Multivariate model including CA125, estimated glomerular filtration rate, E/e’, and left ventricular ejection fraction showed acceptable prognostic potential (C-index = 0.829, 95% CI: 0.749–0.909). CA125 remained an independent prognostic factor (HR = 1.018, 95% CI: 1.005–1.031, p = 0.008, per 10 U/mL increase) after adjusting for the remaining three variates and provided a significant incremental effect to the risk determined from them (C-index 0.829 vs. 0.784, p = 0.037). Conclusion: Serum CA125 level was associated with long-term prognosis of AL cardiorenal amyloidosis.

A Struma Ovarii Associated with Pseudo-Meigs’ Syndrome is Misdiagnosed as Advanced Ovarian Cancer: A Case Report

Introduction: A struma ovarii is a benign monodermal teratoma, composed of mature thyroid tissue. The presentation of this disease with pseudo-Meigs’ syndrome [characterized by ascites, pleural effusions, and elevated cancer antigen-125 (CA-125) levels] may result in an advanced ovarian cancer misdiagnosis. Case Presentation: The patient was a 54-year-old woman with dyspnea, abdominal distention, and pseudo-Meigs’ syndrome. She had a final diagnosis of struma ovarii, misdiagnosed as advanced ovarian cancer. She is currently asymptomatic (after surgery) and has a normal CA-125 level. Conclusions: The preoperative diagnosis of struma ovarii is difficult, and if it presents with pseudo-Meigs’ syndrome, it may be initially misdiagnosed as advanced ovarian cancer. Using the frozen-section procedure, unnecessary extensive surgeries can be prevented.

CA125 test result, test-to-diagnosis interval, and stage in ovarian cancer at diagnosis: a retrospective cohort study using electronic health records.

BackgroundIn the UK, the cancer antigen 125 (CA125) test is recommended as a first-line investigation in women with symptoms of possible ovarian cancer.AimTo compare time between initial primary care CA125 test and diagnosis, tumour morphology, and stage in women with normal (<35 U/ml) and abnormal (≥35 U/ml) CA125 levels prior to ovarian cancer diagnosis.Design and settingRetrospective cohort study using English primary care and cancer registry data.MethodAssociations between CA125 test results and test-to-diagnosis interval, stage, and ovarian cancer morphology were examined.ResultsIn total, 456 women were diagnosed with ovarian cancer in the 12 months after having a CA125 test. Of these, 351 (77%) had an abnormal, and 105 (23%) had a normal, CA125 test result. The median test-to-diagnosis interval was 35 days (interquartile range [IQR] 21–53) for those with abnormal CA125 levels, and 64 days (IQR 42–127) for normal CA125 levels. Tumour morphology differed by CA125 result: indolent borderline tumours were less common in those with abnormal CA125 levels (n = 47, 13%) than those with normal CA125 levels (n = 51, 49%) (P<0.001). Staging data were available for 304 women with abnormal, and 77 with normal, CA125 levels. Of those with abnormal CA125 levels, 35% (n = 106) were diagnosed at an early stage, compared to 86% (n = 66) of women with normal levels. The odds of being diagnosed with early-stage disease were higher in women with normal as opposed to abnormal CA125 levels (odds ratio 12.2, 95% confidence interval = 5.8 to 25.1, P<0.001).ConclusionDespite longer intervals between testing and diagnosis, women with normal, compared with abnormal, CA125 levels more frequently had indolent tumours and were more commonly diagnosed at an early stage in the course of the disease. Although testing approaches that have greater sensitivity might expedite diagnosis for some women, it is not known if this would translate to earlier-stage diagnosis.

Elevated CA-125 Level and ER-Negative as Prognostic Factors for Ovarian Metastasis in Patients with Endometrial Cancer: A Retrospective Cohort Study.

BackgroundThe utility of cancer antigen 125 (CA-125), estrogen receptor (ER), and progesterone receptor (PR) in evaluation for ovarian metastasis of endometrial cancer has yet to be determined. The purpose of this study was to investigate the incidence and the possible risk factors of ovarian metastasis.Material/MethodsA retrospective study was performed in endometrial cancer patients who accepted surgical intervention of hysterectomy and oophorectomy during 2002–2013 in Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China. Clinico-pathologic characteristics and the possible risk factors were investigated.ResultsA total of 565 patients were identified, of which 5.7% had ovarian metastasis. Univariate analysis and multivariate analysis revealed that deeper myometrial invasion, tubal involvement, and parametrial involvement were independent risk factors. In subgroup analysis, univariate analysis showed that elevated CA-125 level and negative ER were associated with ovarian metastasis (P<0.05), however multivariate analysis revealed that only high CA-125 level was an independent risk factor (P<0.05). The incidence of ovarian metastasis in patients with high CA-125 level and who were ER-negative was 24%. For patients with normal CA-125 level and who were ER-positive, the incidence was 1.19%. The optimal cutoff value that provided the best sensitivity and specificity was 110.5 U/ml.ConclusionsThe incidence of ovarian metastasis in endometrial cancer is low. Ovarian preservation should be considered for women without abnormal CA-125 level and who have deeper myometrial invasion, tubal involvement, parametrial involvement, and who are ER-negative. These findings may facilitate clinical decision-making.

Prognostic significance of CA-125 re-elevation after interval debulking surgery in patients with advanced-stage ovarian cancer undergoing neoadjuvant chemotherapy

AimsWe evaluated the prognostic significance of postoperative re-elevation of cancer antigen-125 (CA-125) levels in patients with ovarian cancer and preoperative normalization of CA-125 levels after neoadjuvant chemotherapy (NAC). MethodsThe data of 103 patients with preoperative CA-125 normalization after NAC at the Yonsei Cancer Hospital (2006–2017) were analyzed. We compared the clinical characteristics and survival outcomes among patients with normal postoperative CA-125 levels and those with re-elevated CA-125 levels after interval debulking surgery (IDS). CA-125 elevation was defined as levels >35 U/mL. ResultsAmong 103 patients, 52 (50.5%) and 51 (49.5%) had normal and re-elevated CA-125 levels after IDS, respectively. Patients with CA-125 re-elevation underwent more radical surgeries during IDS than those with normal CA-125 levels (p = 0.018). We found no significant differences in progression-free survival (PFS; p = 0.726) or overall survival (OS; p = 0.293) between the two groups. Moreover, patients with persistent CA-125 elevation (3 weeks after IDS) did not have inferior PFS (p = 0.171 and p = 0.208, respectively) or OS (p = 0.128 and p = 0.095, respectively) compared to patients with early normalization (within 3 weeks of IDS) or normal CA-125 levels. Multivariate regression showed that CA-125 re-elevation had no effect on recurrence (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.43–1.30) or death (HR, 0.99; 95% CI, 0.33–2.98). ConclusionAmong patients with preoperative CA-125 normalization after NAC, postoperative CA-125 re-elevation had no prognostic value. Novel and reliable biomarkers reflecting the tumor response after IDS should be identified.

Usefulness of CA125 and their kinetic parameters and positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose ([18F] FDG) in the detection of recurrent ovarian cancer levels

Background and objectiveTo assess the usefulness of cancer antigen 125 (CA125) serum levels and kinetic values, velocity (CA125vel) and doubling time (CA125dt), as well as fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), in the detection of ovarian cancer recurrence. To assess the optimal cut-off for CA125, CA125vel and CA125dt to detect relapse with [18F]FDG-PET/CT. Material and methodsA retrospective analysis was performed of 59 [18F]FDG-PET/CT (48 patients) for suspected recurrence of ovarian cancer. Receiver operating characteristic (ROC) curves were plotted and area-under-the curve (AUC) statistics were computed for CA125, CA125vel and CA125dt. The results obtained in the group with normal and high (>35U/ml) CA125 levels were compared. ResultsForty-four cases of recurrence were diagnosed (7 had CA125 ≤35U/ml), whereas 15 showed no disease. All of them were correctly catalogued by PET/CT. In ROC analysis, the discriminatory power of CA125 was relatively high (AUC 0.835) and the optimal cut-off point to reflect active disease was 23.9U/ml. The ROC analyses for the CA125vel and CA125dt showed an AUC of 0.849 and 0.728, respectively, with an optimal cut-off point of 1.96U/ml/month and 0.76 months, respectively. In patients with normal CA125 and recurrence of ovarian cancer, the CA125vel was significantly higher than in patients without recurrence (p=0.029). Conclusion[18F]FDG-PET/CT is more accurate than CA125 parameters in the detection of ovarian cancer recurrence. CA125 serum levels are essential; nevertheless, CA125 kinetic values must be considered to detect relapse. Particularly in patients with CA125 within normal values, in which a higher CA125vel is indicative of recurrence.

CA-125 Significance in Cirrhosis and Correlation with Disease Severity and Portal Hypertension: A Retrospective Study

Background and Aims: To evaluate the prevalence and significance of elevated cancer antigen-125 (CA-125) levels in patients with cirrhosis being treated in a tertiary care liver center and its correlation with objective markers of disease severity.Methods: We retrospectively reviewed medical records of 172 adult patients with cirrhosis (due to any etiology) after obtaining CA-125 serum analysis. Demographics, etiology of cirrhosis, model of end-stage liver disease (MELD) score, Child’s Turcotte-Pugh classification, albumin bilirubin (ALBI) score, degree of ascites, presence of esophageal varices, serum CA-125 level and various other parameters were collected. Statistical analysis was performed using SPSS software and descriptive statistics.Results: Elevated CA-125 levels were noted in 147 patients (85%) of the study population. Higher MELD score was associated with higher CA-125 levels (p = 0.001). Statistically significant correlation was observed between elevated CA-125 levels and degree of ascites (p < 0.001), ALBI score (p < 0.001) and Child’s Turcotte-Pugh class (p < 0.001). No correlation was observed with presence or absence of esophageal varices. Near-normal CA-125 levels were noted in patients with cirrhosis but undetectable ascites on ultrasound imaging. No differences were observed in mean values between male and female patients (p = 0.207). Regression analysis confirmed that CA-125 levels had a better correlation with degree of ascites than MELD score or ALBI score.Conclusions: Elevated CA-125 levels were noted in 85% of patients with cirrhosis at our center. Our study establishes that the more advanced the degree of decompensation based on MELD score, Child’s Turcotte-Pugh classification and ALBI score, the higher the elevation in CA-125. Absence of ascites was associated with normal CA-125 level, with a direct correlation between high levels and worsening ascites, but there was no statistically significant correlation with esophageal varices, indicating that elevated CA-125 levels could be related to mechanical stretch of the peritoneum rather than portal hypertension itself. Further multi-centered studies are required to confirm and validate these findings.

Usefulness of CA125 and its kinetic parameters and positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose ([18F] FDG) in the detection of recurrent ovarian cancer

Background and objectiveTo assess the usefulness of cancer antigen 125 (CA125) serum levels and kinetic values, velocity (CA125vel) and doubling time (CA125dt), as well as fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), in the detection of ovarian cancer recurrence. To assess the optimal cut-off for CA125, CA125vel and CA125dt to detect relapse with [18F]FDG-PET/CT. Material and methodsA retrospective analysis was performed of 59 [18F]FDG-PET/CT (48 patients) for suspected recurrence of ovarian cancer. Receiver operating characteristic (ROC) curves were plotted and area-under-the curve (AUC) statistics were computed for CA125, CA125vel and CA125dt. The results obtained in the group with normal and high (>35U/ml) CA125 levels were compared. ResultsForty-four cases of recurrence were diagnosed (7 had CA125 ≤35U/ml), whereas 15 showed no disease. All of them were correctly catalogued by PET/CT. In ROC analysis, the discriminatory power of CA125 was relatively high (AUC 0.835) and the optimal cut-off point to reflect active disease was 23.9U/ml. The ROC analyses for the CA125vel and CA125dt showed an AUC of 0.849 and 0.728, respectively, with an optimal cut-off point of 1.96U/ml/month and 0.76 months, respectively. In patients with normal CA125 and recurrence of ovarian cancer, the CA125vel was significantly higher than in patients without recurrence (p=0.029). Conclusion[18F]FDG-PET/CT is more accurate than CA125 parameters in the detection of ovarian cancer recurrence. CA125 serum levels are essential; nevertheless, CA125 kinetic values must be considered to detect relapse. Particularly in patients with CA125 within normal values, in which a higher CA125vel is indicative of recurrence.

Stage IA Ovarian Cancers

The purpose of this study was to compare sonographic findings and histopathologic types of stage IA ovarian cancers between groups with normal and elevated cancer antigen 125 (CA-125) levels. Between 2000 and 2009, 146 stage IA ovarian cancers were treated surgically (85 invasive and 61 borderline, 73 self-referred with tumor-related symptoms, 20 self-referred with nonspecific symptoms, 52 identified through screening, and 1 other). Of these, 87 cases (60%) had normal serum CA-125 levels (<35 U/mL). Their pre-operative sonographic findings and histopathologic types were compared to those of cases with elevated CA-125 levels. Statistically significant differences were found between the proportions of patients with elevated CA-125 levels in groups having tumors with maximal diameters of less than 20 cm and at least 20 cm (P = .03) and groups having tumors with less than 50% and 50% to 80% solid components (P = .02). In the group with normal CA-125 levels, we found predominantly mucinous adenocarcinoma in multilocular cysts with less than 50% solid components (25 cases), and clear cell adenocarcinoma in unilocular cysts with less than 50% solid components (12 cases), whereas in the group with elevated CA-125 levels, mucinous adenocarcinoma in multilocular cysts with less than 50% solid components (19 cases) and endometrioid adenocarcinoma in solid tumors (≥80% solid components) were predominant (5 cases). Stage IA ovarian cancers with normal CA-125 levels tend to be smaller, have less solid components, and have a slightly different distribution of histopathologic types than cancers with elevated CA-125 levels.

Abstract 2818: Urinary MMP-2 and MMP-9 predict the presence of ovarian cancer in women with normal CA125 levels

Abstract Currently, the only widely used biomarker for monitoring ovarian cancer status and response to therapy is the cancer antigen 125 (CA125). Interestingly, the majority of newly developed ovarian cancer multi-marker assays also rely heavily on serum CA125 levels as one of the biomarkers in their panels. However, 20% of women with advanced ovarian cancer have blood CA125 levels within the normal range of 35 U/mL and below. These women represent a cohort of patients for whom no clinically useful biomarkers are available for monitoring disease status, stage or response to therapy. To address this need, we asked whether a panel of urinary biomarkers that we have previously validated for use in other cancers, could predict the presence of disease in women with ovarian cancer possessing normal CA125 levels. Urine samples were collected from 81 healthy controls and 26 ovarian cancer patients with blood CA125 levels below 35 U/mL. Using monospecific ELISAs, we determined that urinary levels of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) and the neutrophil gelatinase lipocalin 2 (NGAL) are detected at significantly higher levels in the urine of ovarian cancer patients than in the urine of healthy controls. Additionally, receiver-operating characteristic (ROC) area under the curve (AUC) analysis of these groups revealed that, individually, MMP-2, MMP-9 and NGAL each could significantly distinguish ovarian cancer patients with CA125 &amp;lt; 35 U/mL from controls. The best combination of biomarkers for predicting the presence of disease was MMP-2 plus MMP-9 with an ROC AUC of 0.7332 (P&amp;lt;0.01). When these biomarkers were multiplexed with age, a know risk factor of ovarian cancer, the diagnostic accuracy of these biomarkers increased to an AUC of 0.820 (P&amp;lt;0.001). This combination of urinary MMP-2, MMP-9 and age demonstrated excellent diagnostic capability in differentiating ovarian cancer patients from healthy controls among the cohort of patients for whom CA125 values were uninformative. Acknowledgments: The authors gratefully acknowledge the support of Ovations for the Cure of Ovarian Cancer (MAM and UAM) and the Stuart Weitzman Foundation (MAM). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2818. doi:10.1158/1538-7445.AM2011-2818

A long-term survivor of repeated inguinal nodes recurrence of papillary serous adenocarcinoma of CUP: case report.

BackgroundTumor spread beyond the peritoneal cavity in cases of papillary serous adenocarcinoma of the unknown primary (CUP) is a rare late event and carries a poor prognosis.Case presentationA 71-year-old female was referred to our hospital because of a large right inguinal tumor with biopsy evidence of carcinoma as well as an elevated serum CA125 (cancer antigen 125). She underwent complete resection of the right inguinal tumor and multiple pelvic tumors, which involved the rectum, ovary and uterus. Pathological examination revealed the tumors to be metastases of a papillary serous adenocarcinoma with a psammoma body of CUP. On the 28th postoperative day, newly developed asymptomatic small left inguinal node metastases in the setting of a normal CA125 level were removed. Four and a half years after the primary resection, the CA125 level increased again and newly developed asymptomatic metastases were found in the right deep inguinal nodes and extirpated at that time. All surgical resections followed the modified FAM (5FU, Adriamycin; ADM, MMC) regimen, including protracted dairy oral administration of UFT or 5'-FDUR, Cimetidine and PSK (protein-bound polysaccharide K) as an immunomodulator or biological response modifier in conjunction with intermittent one-day continuous infusion (ADM+MMC) or intermittent single bolus injection of ADM+MMC. At present, the patient has been living in good health for almost 7 years with no evidence of relapse.ConclusionAggressive resection surgery followed by effective adjuvant chemotherapy is necessary for surviving long time without relapse of poorly prognostic patients with metastases outside of the abdominal cavity from peritoneal papillary serous adenocarcinomas.

Tumor-associated trypsin inhibitor and cancer antigen 125 in pelvic masses

Tumor-associated trypsin inhibitor (TATI) and cancer antigen 125 (CA-125) were measured pre- and peroperatively in 183 patients with a pelvic mass to elucidate the value of TATI alone and in combination with CA-125 as a differential diagnostic tool. Malignant tumors were registered in 109 patients (90 ovarian and 19 nonovarian cases), borderline ovarian tumors in 8, and benign tumors in 66 (50 ovarian and 16 nonovarian). The TATI level was increased only in half of the patients with malignant tumors; therefore, the marker cannot be used alone as a preoperative diagnostic tool. In contrast, CA-125 had a sensitivity of 82%, which rose to 91% when the marker was used in combination with TATI. CA-125 and TATI had a combined specificity of 76% and positive and negative predictive values of 87 and 83%, respectively. Our results indicate that TATI measurement substantially improves the preoperative differential diagnostic information obtained with CA-125 and that it does not significantly increase the number of false-positive findings. We recommend the complementary measurement of TATI in patients who have a pelvic mass and a normal CA-125 level.

Tumor-associated trypsin inhibitor and cancer antigen 125 in pelvic masses

Tumor-associated trypsin inhibitor (TATI) and cancer antigen 125 (CA-125) were measured pre- and peroperatively in 183 patients with a pelvic mass to elucidate the value of TATI alone and in combination with CA-125 as a differential diagnostic tool. Malignant tumors were registered in 109 patients (90 ovarian and 19 nonovarian cases), borderline ovarian tumors in 8, and benign tumors in 66 (50 ovarian and 16 nonovarian). The TATI level was increased only in half of the patients with malignant tumors; therefore, the marker cannot be used alone as a preoperative diagnostic tool. In contrast, CA-125 had a sensitivity of 82%, which rose to 91% when the marker was used in combination with TATI. CA-125 and TATI had a combined specificity of 76% and positive and negative predictive values of 87 and 83%, respectively. Our results indicate that TATI measurement substantially improves the preoperative differential diagnostic information obtained with CA-125 and that it does not significantly increase the number of false-positive findings. We recommend the complementary measurement of TATI in patients who have a pelvic mass and a normal CA-125 level.