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Serum biomarkers provide valuable information about the diagnosis and prognosis of a wide variety of malignant tumors. Despite the identification of several useful serum biomarkers in lung cancer, consensus on their utility has not yet been reached. Furthermore, guidelines and standard protocols to implement their use for patients with lung cancer are lacking, despite the accumulation of much data on the efficacy of several serum biomarkers over recent decades. In this review, we discuss the molecular features, functions, and clinical relevance of the conventional serum biomarkers for lung cancer, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA 21-1), tissue polypeptide antigen (TPA), carbohydrate antigen 19-9 (CA19-9), sialyl Lewis x (sLe x ), carbohydrate antigen 125 (CA-125), squamous cell carcinoma-related antigen (SCC-Ag), neuron-specific enolase (NSE), and pro-gastrin-releasing peptide (proGRP), aiming to provide a snapshot of the current landscape and their potential combined utility in the diagnosis and prognosis of lung cancer.

Background: The aim of the present study was to investigate the predictive performance of serial tissue polypeptide antigen (TPA) testing after curative intent resection for detection of recurrence of colorectal malignancy., Methods: Serum samples were obtained in 572 patients from three different hospitals during follow-up after surgery. Test characteristics of serial TPA testing were assessed using a cut-off value of 75 U/L. The relation with American Joint Committee on Cancer stage and the potential additive value of tissue polypeptide antigen testing upon standard carcinoembryonic antigen (CEA) testing were investigated., Results: The area under the receiver operating characteristic curve of TPA for recurrent disease was 0.70, indicating marginal usefulness as a predictive test. Forty percent of cases that were detected by CEA testing would have been missed by TPA testing alone, whilst most cases missed by CEA were also not detected by TPA testing. In the subpopulation of patients with stage III disease predictive performance was good (area under the curve 0.92 within 30 days of diagnosing recurrent disease). In this group of patients, 86% of cases that were detected by CEA were also detected by TPA., Conclusions: Overall, TPA is a relatively poor predictor for recurrent disease during follow-up. When looking at the specific subpopulation of patients with stage III disease predictive performance of TPA was good. However, TPA testing was not found to be superior to CEA testing in this specific subpopulation.

Aim: The aim of the study was to assess the degree to which tissue polypeptide antigen (TPA) and tissue polypeptide-specific antigen (TPS), as well as carcinoembryonic antigen (CEA), can assist in the detection of distant metastases., Patients and Methods: We assessed 157 patients with colorectal and breast cancer divided into two groups. The first was a group of patients with cancer at stages 1, 2 and 3; the second was a group of patients with cancer at stage 4 with metastasis., Results: We found significantly higher levels of all biomarkers in the metastatic group compared to the group with cancer at stages 1-3 (p<0.0001). The calculated area under the receiver operating characteristic (ROC) curve was 0.9929 for TPS, 0.9337 for TPA and 0.7234 for CEA. The cut-off was calculated for each biomarker at 95% specificity, TPS cut-off=255 IU/l (sensitivity 95%), TPA cut-off=200 IU/l (sensitivity 70%) and CEA cut-off=18 μg/l (sensitivity 37%)., Conclusion: We suggest combining CEA with TPS or TPA in the detection of distant metastases or using only cytokeratins. This approach can significantly increase the quality of detection of the metastatic process., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

A novel sandwich-type electrochemical immunoassay with sensitivity enhancement was developed for quantitative detection of tissue polypeptide antigen (TPA) by coupling with target-induced tyramine signal amplification on prussian blue-gold hybrid nanostructures. The immunosensor was prepared through immobilizing anti-TPA capture antibody on a cleaned screen-printed carbon electrode (SPCE). Prussian blue-gold hybrid nanostructures (PBGNS) labeled with horseradish peroxidase (HRP) and detection antibody were utilized as the signal-transduction tags. Upon target TPA introduction, the sandwiched immunocomplex was formed between capture antibody and detection antibody on the electrode. The carried HRP could trigger the formation of tyramine-HRP repeats on the PBGNS in the presence of H2O2. Using the doped prussian blue as the electron mediator, the conjugated HRP could catalyze the reduction of H2O2. Under the optimal conditions, the catalytic currents increased with the increasing target TPA in the dynamic range from 1.0 pg mL(-1) to 100 ng mL(-1) with a detection limit of 0.3 pg mL(-1). The reproducibility and specificity of the electrochemical immunoassay were acceptable. In addition, the contents of target TPA in nine human serum specimens were evaluated by using the developed electrochemical immunosensor, and the obtained results correlated well with those from commercially enzyme-linked immunosorbent assay (ELISA) method with a correlation coefficient of 0.9975., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The serological protein tumor markers CA 15-3, CEA, and TPA are frequently used to monitor tumor burden among metastatic breast cancer patients. Breast cancer is associated with global DNA hypomethylation and hypermethylation of some promoter regions. No monitoring study has yet investigated the interrelationship between protein tumor markers, the global DNA hypomethylation, and hypermethylated genes in serum from patients with advanced disease. Twenty-nine patients with histologically proven advanced breast cancer received first-line chemotherapy with epirubicin. Samples were collected prior to each treatment and prospectively analyzed for CA 15-3, CEA, and TPA. The same samples were retrospectively analyzed for the concentration of hypermethylated RASSF1A and for global DNA hypomethylation using LINE-1. Among patients with elevated concentrations of the protein markers, concordance could be observed between serial changes of the hypermethylated RASSF1A gene and the protein markers. Among patients with lower concentrations, RASSF1A could only be detected periodically. There was discordance between changes of the hypomethylated LINE-1 as compared to the protein markers. Circulating hypermethylated RASSF1A and protein markers may have similar kinetics during monitoring of tumor burden. Further investigations are needed to determine whether any of the hypermethylated DNA genes may provide predictive information during monitoring.

This study clarifies the relationship between clinical and laboratory patterns, in endocrine-responsive metastatic breast cancer patients treated with a cyclic beta-interferon and interleukin-2 sequence added to anti-estrogens. In 31 patients, a regular laboratory and immunological assessment was made. During clinical benefit, as opposed to progression, a significant increase in the total number of lymphocytes, CD4+, CD8+, NK cells, CRP and IL-12 was confirmed. Also, a significant CEA, TPA, CA15.3 decrease occurred 24-72h after interleukin-2 administration. At the progression, both basally and after interleukin-2 stimulation, the mean values of CD4+ plus CD25+ cells were more than twice higher than during clinical benefit, with a decrease of CD4+ plus CD8+ (Teffector)/CD4+CD25+ (Treg) ratio. Moreover, a significant increase for CEA and for all 3 markers (standardized values) was found 24-72h after interleukin-2 administration. In patients who survived less than 5years, the Treg cell increase occurred at a significantly shorter time interval than in those who survived longer than 5years (20 vs 45.5months, respectively; P=0.001). These data show laboratory evidence of the effect of immunotherapy as well as that of hormone resistance occuring concomitantly with a laboratory pattern compatible with immune inhibition., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

A sandwich-type immunosensor was developed for the detection of human tissue polypeptide antigen (hTPA). In this work, a graphene sheet (GS) was synthesized to modify the surface of a glassy carbon electrode (GCE), and Pd-Pt bimetallic nanocrystals were used as secondary-antibody (Ab2) labels for the fabrication of the immunosensor. The amperometric response of the immunosensor for catalyzing hydrogen peroxide (H2O2) was recorded. And electrochemical impedance spectroscopy was used to characterize the fabrication process of the immunosensor. The anti-human tissue polypeptide antigen primary antibody (Ab1) was immobilized onto the GS modified GCE via cross-linking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide (EDC/NHS). With Ab1 immobilized onto the GS modified GCE and Ab2 linked on Pd-Pt bimetallic nanocrystals, the immunosensor demonstrated a wide linear range (0.0050-15 ng ml(-1)), a low detection limit (1.2 pg ml(-1)), good reproducibility, good selectivity and acceptable stability. This design strategy may provide many potential applications in the detection of other cancer biomarkers.

To evaluate the value of combined detection of serum CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS for the clinical diagnosis of upper gastrointestinal tract (GIT) cancer and to analyze the efficacy of these tumor markers (TMs) in evaluating curative effects and prognosis. A total of 573 patients with upper GIT cancer between January 2004 and December 2007 were enrolled in this study. Serum levels of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were examined preoperatively and every 3 months postoperatively by ELISA. The sensitivity of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were 26.8%, 36.2%, 42.9%, 2.84%, 25.4%, 34.6%, 34.2% and 30.9%, respectively. The combined detection of CEA+CA199+CA242+CA724 had higher sensitivity and specificity in gastric cancer (GC) and cardiac cancer, while CEA+CA199+CA242+SCC was the best combination of diagnosis for esophageal cancer (EC). Elevation of preoperative CEA, CA19-9 and CA24-2, SCC and CA72-4 was significantly associated with pathological types (p<0.05) and TNM staging (p<0.05). Correlation analysis showed that CA24-2 was significantly correlated with CA19-9 (r=0.810, p<0.001). The levels of CEA, CA19-9, CA24-2, CA72-4 and SCC decreased obviously 3 months after operations. When metastasis and recurrence occurred, the levels of TMs significantly increased. On multivariate analysis, high preoperative CA72-4, CA24-2 and SCC served as prognostic factors for cardiac carcinoma, GC and EC, respectively. combined detection of CEA+CA199+CA242+SCC proved to be the most economic and practical strategy in diagnosis of EC; CEA+CA199+CA242+CA724 proved to be a better evaluation indicator for cardiac cancer and GC. CEA and CA19-9, CA24-2, CA72-4 and SCC, examined postoperatively during follow-up, were useful to find early tumor recurrence and metastasis, and evaluate prognosis. AFP, TPA and TPS have no significant value in diagnosis of patients with upper GIT cancer.

Background: To determine the potential clinical utility of tumor markers CEA, TPA, and SCC-Ag for early detection of cervical precancerous lesions., Materials and Methods: A case-control study was carried out on 120 women (46 patients with histologically confirmed cervical precancerous lesions and 74 healthy controls). The significance of serum selected tumor markers in early detection of cervical intraepithelial neoplasia (CIN) were assessed., Results: Of the case group, the rates of CIN I, II, III, was 69.6%, 23.9%, and 6.5%, respectively. According to the manufacturer's cut-off values of 2 ng/ml, 5 ng/ml, and 70 U/ml for SCC-Ag, CEA and TPA tests, in that order, SCC-Ag test had a sensitivity of 13%, but CEA and TPA tests could not distinguish between case and control groups. The diagnostic sensitivities were highest at cut-off values of 0.55 ng/ml for SCC-Ag, 2.6 ng/ ml for CEA, and 25.5 U/ml for TPA which were 93%, 61%, and 50%, respectively. However, the area under the receiver operating characteristic curve was the largest for SCC-Ag (0.95 vs. 0.61 and 0.60 for CEA and TPA, respectively). Moreover, there was a highly significant direct correlation between SCC-Ag concentration and the degree of cervical precancerous lesions (r=0.847, p<0.001)., Conclusions: The new cutoff of 0.5 for SCC-Ag test might be useful as a tumor marker in Iranian patients with CIN and it needs to be more evaluated by studies with larger populationa.

The higher incidence of breast cancer in developed countries has been tempered by reductions in mortality, largely attributable to mammographic screening programmes and advances in adjuvant therapy. Optimal systemic management requires consideration of clinical, pathological and biological parameters. Oestrogen receptor alpha (ERα), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) are established biomarkers evaluated at diagnosis, which identify cardinal subtypes of breast cancer. Their prognostic and predictive utility effectively guides systemic treatment with endocrine, anti-HER2 and chemotherapy. Hence, accurate and reliable determination remains of paramount importance. However, the goals of personalized medicine and targeted therapies demand further information regarding residual risk and potential benefit of additional treatments in specific circumstances. The need for biomarkers which are fit for purpose, and the demands placed upon them, is therefore expected to increase. Technological advances, in particular high-throughput global gene expression profiling, have generated multi-gene signatures providing further prognostic and predictive information. The rational integration of routinely evaluated clinico-pathological parameters with key indicators of biological activity, such as proliferation markers, also provides a ready opportunity to improve the information available to guide systemic therapy decisions. The additional value of such information and its proper place in patient management is currently under evaluation in prospective clinical trials. Expanding the utility of biomarkers to lower resource settings requires an emphasis on cost effectiveness, quality assurance and possible international variations in tumor biology; the potential for improved clinical outcomes should be justified against logistical and economic considerations., (Copyright © 2012 UICC.)

Background: To evaluate the predictive and prognostic value of serum and plasma tumor markers, in comparison with clinical and biomedical parameters for response rate (RR), progression-free survival (PFS) and overall survival (OS) among patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy., Material and Methods: One-hundred and six patients with mCRC from three centers, part of a multicenter study, received irinotecan with the Nordic bolus 5-fluorouracil (5-FU) and folinic acid schedule (FLIRI) or the de Gramont schedule (Lv5FU2-IRI). Blood samples for CEA, CA19-9, TPA, TIMP-1, SAA, transthyretin and CRP were taken at baseline and after two, four and eight weeks of treatment. Tumor marker levels at baseline and longitudinally were compared with responses evaluated (CT/MRI) after two and four months of treatment. The correlations to RR, PFS and OS were evaluated with regression analyses., Results: A significant correlation to OS was seen for baseline levels of all markers. In multivariate analyses with clinical parameters, TPA, CRP, SAA and TIMP-1 provided independent information. The baseline values of CEA, TPA and TIMP-1 were also significantly correlated to PFS and TPA to RR. Changes during treatment, i.e. the slope gave with the exception of CA19-9 for OS less information about outcomes. The best correlation to response was seen for CEA, CA19-9 and TPA with AUC values of 0.78, 0.83 and 0.79, respectively, using a combined model based upon an interaction between the slope and the baseline value., Conclusions: Baseline tumor markers together with clinical parameters provide prognostic information about survival in patients with mCRC. The ability of the individual tumor markers to predict treatment response and PFS is limited. Changes in marker levels during the first two months of treatment are less informative of outcome.

Based on the specificity of the immunoreaction of anti-body and antigen, and the resulting localized surface plasmon resonance extinction response of functionalized nano-Au monolayer on glass chip, a novel label-free optical immunosensor with amplified sensitivity has been developed for the detection of tissue polypeptide antigen (TPA). The nano-Au monolayer on glass chip was controllably prepared using 3-mercaptopropyltrimethoxysilane (MPTMOS) as linker by a solution self-assembly method. To analyze its quality, the nano-Au monolayer was characterized by UV-visible spectrum and atomic force microscopy (AFM). The resulting chip was modified by tissue polypeptide antigen antibody (anti-TPA), and then bovine serum albumin (BSA) was employed to block the possible remaining active sites of the nano-Au monolayer. An immunosensor was constructed with biocompatible monolayer nano-Au membrane and the desirable TPA antibody/BSA composite membrane, and it showed good selectivity, high sensitivity and a wide linear response to TPA in the range of 1-1000 ng L(-1) with a detection limit of 1.2 x 10(-3) ng L(-1), as well as good stability and long-term life. Owing to its ease of operation, low detection limit and low cost, it is expected that the proposed procedure may hold great promise in both research-based and clinical assays.

Introduction: Portal vein embolization (PVE) is one of the options to increase the number of resecable cases in patients with primary inoperable liver tumors. However, insufficient growth of liver parenchyma or postoperative tumor progression remains problematic in PVE procedures. Generally, tumor markers are of significance in patient postoperative monitoring for the disease recurrence. The aim of this study is to assess the potential of tumor markers in predicting PVE outcomes., Method: The study group included 43 subjects with primary or secondary tumors, in whom serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), thymidine kinase (TK), tissue polypetide antigen (TPS) and MonoTotal levels were assessed 28 days following PVE. The liver parenchyma growth or tumor progression were assessed based on computer tomography., Results: Sufficient liver parenchyma hypertrophy was recorded in 27 (62.8 %) patients with subsequent liver resection. Insufficient post-PVE liver parenchyma growth was recorded in 5 (11.6 %) patients and tumor progression was recorded in 11 (25.6 %) subjects. The following tests were considered significant predictive tumor markers of PVE outcomes: serum levels of CEA, TPA, Mono Total prior to PVE, and serum levels of TK, TPA, Mono Total within 28 days following PVE., Conclusion: Tumor markers may be significant in predicting PVE outcomes in patients with primary inoperable liver tumors. However, in order to make final conclusions on their clinical significance, larger patient group studies should be performed.

Aim: The liver is the site of breast cancer metastasis in 50% of patients with advanced disease. Tumour markers have been demonstrated as being useful in follow-up of patients with breast cancer, in early detection of recurrence of breast cancer after radical surgical treatments, and in assessing oncologic therapy effect, but no study has been carried out on their usefullness in distinguishing benign liver lesions from breast cancer metastases. The aim of this study was therefore to evaluate the importance of tumour markers carcinoembryonic antigen (CEA), carbohydrate antigen CA19-9 (CA19-9), thymidine kinase (TK), tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and cytokeratin 19 fragment (CYFRA 21-1) in differential diagnosis between benign liver lesions and liver metastases of breast cancer., Patients and Methods: The study includes 3 groups: 22 patients with liver metastases of breast cancer; 39 patients with benign liver lesions (hemangioma, focal nodular hyperplasia, liver cyst, hepatocellular adenoma); and 21 patients without any liver disease or lesion that were operated on for benign extrahepatic diseases (groin hernia, varices of lower limbs) as a control group. The serum levels of tumour markers were assessed by means of immunoanalytical methods., Results: Preoperative serum levels of CYFRA 21-1, TPA, TPS and CEA were significantly higher in patients with liver metastases of breast cancer in contrast to healthy controls and patients with benign liver lesions (p-value<0.05). Serum levels of CA19-9 and TK were higher in patients with malignancy in comparison with benign liver disease and healthy controls but these differences were not statistically significant., Conclusion: Tumour markers CEA, CYFRA 21-1, TPA and TPS can be recommended as a good tool for differential diagnosis between liver metastases of breast cancer and benign liver lesions.

Human oral cancer has a high risk of locoregional relapse which is difficult to diagnose early due to lack of prognostic markers. We and others have shown aberrant expression of cytokeratin (CK) 8 and 18 in human oral cancer. Aberrant supra-basal expression of CK19 has been shown earlier. In this study, our aim was to develop a non-invasive test for prognostication of human oral cancer. Immunoradiometric assay (IRMA) was used to measure the circulating levels of TPA in the sera of 80 oral cancer patients before surgery and seven days after surgery. Elevated serum TPA levels were noted in the post surgery samples of 28 out of the 50 patients for whom clinical follow-up was available, as compared to their pre-surgery samples. TPA levels in the pre-surgery serum samples of patients were significantly higher than levels in the sera of healthy controls (p=0.001). Elevated levels in patients correlated significantly with stage (p=0.02), development of recurrence (p<0.006), and impacted survival (p<0.033). IHC analysis showed statistically significant correlation between expression of CK8, 18 and 19 in surrounding uninvolved tissues of the tumour and post surgery elevated serum TPA levels (p<0.001). This suggests the possibility that CK fragments are released from the surrounding uninvolved tissues into the sera of patients after surgical removal of the tumour. Thus, our study indicates that TPA can be a useful tumour marker for the prediction of recurrence and poor prognosis in human oral cancer., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Hypothesis: Intensive risk-adjusted follow-up leads to improved resectability of tumor recurrences and better overall survival among patients who have undergone surgery for colorectal cancer., Design: Long-term observational single-center study., Setting: University of Pisa, Pisa, Italy., Patients: One hundred eight disease-free patients who had undergone surgery for colorectal cancer were submitted to long-term follow-up with the serum CEA, TPA, CA19.9, and CA72.4 tumor marker (TM) panel and abdominal ultrasonography., Main Outcome Measures: Sensitivities and specificities of TMs, abdominal ultrasonography, and abdominal and chest computed tomography (CT); the median survival among patients operated on and those not operated on and the cumulative 5-year overall survival among the entire group., Results: Twenty-two patients with asymptomatic colorectal cancer recurred 32 times. The CEA, TPA, CA19.9, CA72.4, and TM panel sensitivities were 46.9%, 34.4%, 9.4%, 9.4%, and 81.0%, respectively, and the mean (SD) lead times before confirmation of recurrence were 4.3 (4.8), 4.1 (4.7), 8.3 (10.9), 5.0 (7.0), and 5.3 (5.8) months, respectively. Abdominal and chest CT sensitivities were 100.0%. Among 86 patients without recurrence, specificities of the TM panel and all panel markers were 100.0%, while specificities of abdominal ultrasonography, abdominal CT, and skeletal CT were 99.9%, 99.0%, and 100.0%, respectively. The median survival after first recurrence was 16 months (range, 3-48 months) for 8 patients with recurrence who did not undergo second-line surgery. Among 14 remaining patients who underwent metastasectomy, the median survival after first recurrence was 37 months (range, 12-187 months; P = .03). Among the entire group of 108 patients, the cumulative 5-year overall survival was 88.7%., Conclusions: Long-term intensive risk-adjusted monitoring using the CEA, TPA, CA19.9, and CA72.4 TM panel and abdominal ultrasonography allows early detection of most recurrences. Patients can then undergo radical metastasectomy, with potentially improved overall survival.

The incidence of bladder cancer has demonstrated a rapid increase during the last decades. The aim of this study is to determine the clinical value of serum tissue polypeptide antigen (TPA) as a tumour marker for urinary bladder cancer in comparison with conventional urine cytology. Urine and blood samples were obtained from a total of 108 patients (group A) with a known history of bladder cancer, who presented for their routine 3 month follow-up. These 108 patients included 45 patients with high grade and 63 patients with low grade bladder cancer, and 30 patients with lower urinary tract symptoms (LUTS) and no history of bladder cancer (group B). Urine and blood samples from fifty healthy adults (group C) were also tested; this group served as the control group for estimating the normal range of serum TPA values. In all group A patients cystoscopy and/or bladder biopsies were performed. All blood and urine samples were tested for TPA and conventional urine cytology respectively. Results showed that the upper normal range for TPA was 1.0 ng/mL(0.9 ± 0.04) in the control group. For the subgroups of patients with high and low grade bladder cancer elevated serum TPA levels were found in 52% and 40% of the patients respectively. The overall serum TPA sensitivity and specificity were 50% and 85% respectively for patients with known bladder cancer (group A). We found the sensitivity of cytology for high grade bladder (GIII) carcinomas to be 72%; however when urine cytology was combined with serum TPA the overall sensitivity reached 80%. We conclude that serum TPA combined with urine cytology may be used as a prognostic marker for bladder cancer.

Background and Aim: Abnormal serum tissue polypeptide antigen (TPA) values are commonly found in patients with chronic liver damage and liver cirrhosis even in the absence of malignancies. The aim of this study was to compare serum TPA levels in patients with cirrhosis, to examine correlations between TPA levels and the degree of portal hypertension, and to evaluate TPA concentrations in paired hepatic and peripheral blood samples., Methods: A total of 128 patients with chronic liver disease of various severity were studied prospectively. TPA concentrations in hepatic vein and peripheral blood were determined, and Hepatic Vein Pressure Gradient (HVPG) was measured., Results: TPA levels were significantly higher in patients with cirrhosis than in those with chronic hepatitis, and in systemic circulation than in hepatic vein blood. Peripheral but not hepatic TPA levels did correlate with the HVPG. Subjects with clinically significant portal hypertension (HVPG > 10 mmHg) showed significantly higher peripheral TPA levels than those with HVPG < 10 mmHg., Conclusions: Our data suggest that the increased TPA levels observed in cirrhotic patients and the high systemic-to-hepatic blood TPA gradient are probably due to the presence of portal-systemic shunts rather than to hepatic necro-inflammatory activity. In clinical practice, TPA determination could help us to identify and to follow up cirrhotic patients with more severe portal hypertension.

In metastatic breast cancer tumour markers' increase predicts, by a few months (lead time) disease progression. In breast cancer patients with endocrine dependent metastatic disease, we reported a prolonged clinical benefit and overall survival when first line conventional antiestrogen hormone therapy was started at the lead time and also when an immunotherapy schedule was added to the same conventional hormone treatment. Thirty-two of these last patients were considered (group a). In 27 (group b) of these 32 patients who progressed during first line salvage hormone plus immunotherapy the lead time at the progression of metastatic disease during therapy was compared with that at the onset of metastases when the same patients were without treatment and with that of a control group (group c) who did not receive immunotherapy. At disease progression, CEA-TPA-CA15.3 sensitivity was 92.5% in the group b (studied patients) and 88.5% in the group c (controls). At the progression in the group b, CEA-TPA-CA15.3 lead time (m+/-sd, months) was significantly longer than in group c (12.1+/-12.9 vs 2.4+/-4.0) (P=0.000). Besides, in group b the lead time was significantly longer at the progression than at the metastatic onset (P=0.003) while in the group c the difference was near to significance (P=0.05). The CEA-TPA-CA15.3 tumour marker panel accurately predicted metastatic disease progression and immunotherapy significantly prolonged the CEA-TPA-CA15.3 lead time. This can be used for anticipating salvage treatment in these patients.

The cervix is a possible site of metastasis from any primary malignancy, but no specific indication on follow-up examination is present. We present an asymptomatic patient with isolated breast cancer cervical recurrence diagnosed by colposcopy after 11 years from primary disease. After a PubMed search and a review of current guidelines, no indication to follow-up examination regarding the cervix is present. The adoption of colposcopy in cancer survivors might be an aid to gynecologists in diagnosing cancer recurrence. Cancer survivors might benefit from a more thorough gynecologic examination as compared with the simple Papanicolaou test.

Objective: The aim of the study is to asses blood plasma concentrations of S-100B protein and Tissue Polypeptide Antigen (TPA) in patients with confirmed ischemic stroke and to correlate these concentrations with stroke severity., Methods: S-100B protein and TPA blood plasma concentrations were determined in 47 patients with acute ischemic infarction and in the control population. S-100B protein was assessed on the 1th day, TPA on the 1th, 7th and 14th day. The clinical status was documented using Scandinavian Stroke Scale. The functional deficit after the stroke was scored by Barthel Index., Results: The analysis of the entire examined group in relation to the control population showed elevated concentrations of S-100B protein (0.47 ng/ml vs. 0.19 g/ml). The highest concentrations were in the severe stroke group (0.89 ng/ml). The assessment of TPA blood plasma concentrations showed higher ones in the examined group of patients: 225.7 U/l on the 1st day; 96.1 U/l on the 7th day; 125.64 U/l on the 14th day after the stroke in relation to the control population., Conclusion: The analysis of obtained results showed significant increase of S-100B protein blood plasma concentrations in patients with severe stroke and TPA in patients with mild stroke. S-100 protein blood plasma concentration assessed on the 1st day after the ischemic stroke is the parameter presenting the highest diagnostic utility and its value above 0.6 ng/ml was obtained only in patients with severe stroke.

The development of autoimmune diseases may be influenced by hormonal, immunomodulatory, and metabolic pathways. Prolactin (PRL), ferritin, vitamin D, and the tumor marker tissue polypeptide antigen (TPA) were measured in autoimmune diseases: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis (PM), dermatomyositis (DM), multiple sclerosis (MS), autoimmune thyroid diseases, and antiphospholipid syndrome. Hyperprolactinemia (HPRL) was detected in 24% of PM patients, in 21% of SLE patients, in 6.7% of MS patients, 6% of RA patients, and in 3% of SSc patients. Hyperferritinemia was detected in 23% of SLE patients, 15% of DM patients, 8% of MS patients, and 4% of RA patients. The patients had relatively low levels of 25 OH Vitamin D: the average results (mean +/- SD) were between 9.3 +/- 4.4 to 13.7 +/- 7.1 ng/mL in the different diseases, while the 25 OH Vitamin D concentrations less than 20 ng/mL are regarded as deficient. TPA levels were in the same range of the controls, elevated only in SLE. HPRL, hyperferritinemia, hypovitaminosis D, and TPA levels did not correlate with SLE activity elevated levels of rheumatoid factor or anti-CCP antibodies in RA. HPRL, hyperferritinemia, and hypovitaminosis D have different immunological implications in the pathogenesis of the autoimmune diseases. Preventive treatment with vitamin D or therapy for HPRL with dopamine agonists, may be considered in certain cases. Hyperferritinemia may be used as an acute-phase reactant marker in autoimmune diseases mainly SLE. TPA may be used to indicate the tendency for malignancies.

Background: Tumor markers are used for the prediction of relapse and in determining the effect of postoperative or post-oncological therapy as a standard component of follow-up. Metastatic processes of the liver and primary malignancies of the liver and gall bladder are very common in the European population. The aim of this study was to demonstrate the behaviour of malignancy in patients who have not undergone surgical therapy and to study serum levels of the monitored tumor markers in relation to the life expectancy of these patients., Patients and Methods: The Log-rank test and Wilcoxon test were used for statistical evaluation. Survival was computed using the Kaplan-Meier method. Serum levels of the tumor markers conventionally used in clinical practice in patients with gastrointestinal tumors (CEA, CA19-9, C724) and the markers of the proliferation activity in malignancy (TK, TPA, TPS) were studied., Results: One hundred and nine patients who underwent exploratory laparotomy without any surgical therapy between September 1999 and June 2005 were studied. For patients with a serum level of CEA, CA19-9 and CA72-4 that was higher than the calculated cut-off hazard ratios of early death were respectively 3-, 5- and 9-fold higher than for patients with serum levels of the same tumor markers below the calculated cut-off. Preoperative serum levels of proliferative tumor markers (TK, TPA and TPS) were not statistically significant for the prediction of early death., Conclusion: The results of the pilot study suggest the importance of tumor markers for the prediction of the short-term survival rate. These markers could be used to supplement classic clinical, laboratory and radiodiagnostic parameters. It would be very helpful for the planning of palliative oncological therapy for patients with liver malignancies who cannot be treated by surgical therapy.

Cervical carcinoma is the most frequent disease of the female reproductive organs. The tumour markers may be helpful: in early diagnosis of cervical cancer, the initial assesment of the extent of the disease, monitoring of tumour growth or tumour volume reduction, recurrence of cancer, and have been used for monitoring of the clinical course of chemotherapy and radiotherapy. In this paper we have focused on the role of new tumour markers, especially cytokines (for example G-CSF, VEGF) and molecular markers of carcinogenesis (for example Bcl-2 and p53), in comparison to typical tumour markers useful in diagnostic of cervical cancer such as CA 125, SCC-Ag, TPA, TPS, CYFRA 21-1.

Background: In breast cancer current guidelines do not recommend the routine use of serum tumour markers. Differently, we observed that CEA-TPA-CA15.3 (carcinoembryonic (CEA) tissue polypeptide (TPA) and cancer associated 115D8/DF3 (CA15.3) antigens) panel permits early detection and treatment for most relapsing patients. As high sensitivity and specificity and different cut-off values have been reported for mucin-like carcinoma associated antigen (MCA), we compared MCA with the above mentioned tumour markers and MCA-CA15.3 with the CEA-TPA-CA15.3 panel., Methods: In 289 breast cancer patients submitted to an intensive post-operative follow-up with tumour markers, we compared MCA (cut-off values, > or = 11 and > or = 15 U/mL) with CEA or CA15.3 or TPA for detection of relapse. In addition, we compared the MCA-CA15.3 and CEA-TPA-CA15.3 tumour marker panels., Results: Distant metastases occurred 19 times in 18 (6.7%) of the 268 patients who were disease-free at the beginning of the study. MCA sensitivity with both cut-off values was higher than that of CEA or TPA or CA15.3 (68% vs 10%, 26%, 32% and 53% vs 16%, 42%, 32% respectively). With cut-off > or = 11 U/mL, MCA showed the lowest specificity (42%); with cut-off > or = 15 U/mL, MCA specificity was similar to TPA (73% vs 72%) and lower than that of CEA and CA15.3 (96% and 97% respectively). With > or = 15 U/mL MCA cut-off, MCA sensitivity increased from 53% to 58% after its association with CA15.3. Sensitivity of CEA-TPA-CA15.3 panel was 74% (14 of 19 recurrences). Eight of the 14 recurrences early detected with CEA-TPA-CA15.3 presented as a single lesion (oligometastatic disease) (5) or were confined to bony skeleton (3) (26% and 16% respectively of the 19 relapses). With > or = 11 U/mL MCA cut-off, MCA-CA15.3 association showed higher sensitivity but lower specificity, accuracy and positive predictive value than the CEA-TPA-CA15.3 panel., Conclusion: At both the evaluated cut-off values serum MCA sensitivity is higher than that of CEA, TPA or CA15.3 but its specificity is similar to or lower than that of TPA. Overall, CEA-TPA-CA15.3 panel is more accurate than MCA-CA15.3 association and can "early" detect a few relapsed patients with limited metastatic disease and more favourable prognosis. These findings further support the need for prospective randomised clinical trial to assess whether an intensive post-operative follow-up with an appropriate use of serum tumour markers can significantly improve clinical outcome of early detected relapsing patients.

Background: The aim of this study was to examine and compare the value of the serum tumor markers CYFRA 21-1, TPA-M, SCCA and CEA in squamous cell carcinoma (SCC) of the larynx. Moreover, their possible clinical applications were studied., Materials and Methods: The serum levels of CYFRA 21-1, TPA-M, SCCA and CEA were measured in 79 patients with histologically-proven squamous cell carcinoma (SCC) of the larynx before and after treatment and in 77 healthy volunteers. The association of the results with the clinicopathological characteristics was investigated., Results: The study showed that none of the markers revealed a significant sensitivity; TPA-M indicated a positive correlation with the grade of differentiation. CEA indicated a positive correlation only with distant metastasis., Conclusion: Among the four markers, only TPA-M may play a role in monitoring the success of therapy and follow-up in patients with SCC of the larynx.

Investigation: The concentrations of CA 15-3, TPA, and TPS were determined in the serum of 90 women with breast cancer, Material/methods: Serum CA 15-3 levels were determined by Abbott immunofluorescent tests, TPA concentration using the Byk-Roland immunoluminometric method, and TPS by the BEKI Diagnostics immunoenzymatic method., Results: In the diagnosis of breast cancer, the TPA test had the greatest diagnostic sensitivity. A strong correlation was found between the percentages of women with positive levels of all three markers and advanced stages of breast cancer. A longitudinal evaluation of 42 women who underwent neoadjuvant chemotherapy showed clinical regression of the tumor and a statistically significant reduction in the concentrations of these markers, Conclusions: These results indicate that determining the serum levels of CA 15-3, TPA, and TPS may be used to establish the stage of disease and it provides useful guidance both in deciding whether to treat surgically and in estimating the efficacy of neoadjuvant chemotherapy in patients with breast cancer.

Objective: The identification of a reliable circulating tumor marker in squamous cell carcinoma of the head and neck (SCCHN) could assist in diagnosis and monitoring response to therapy., Aim: The aim of this study was to investigate the effectiveness of the serum tumor markers CYFRA 21-1, TPA-M, SCCA, and CEA., Study Design: Serum levels of CYFRA 21-1, TPA-M, SCCA, and CEA were measured in 136 patients with a histologically proven SCCHN before and after treatment and in 125 healthy subjects, as controls. We evaluated the sensitivity and specificity of these tumor markers and to correlate their levels with tumor staging, grading, or performance status., Results: The study showed that none of the above markers presented satisfactory specificity and sensitivity in early diagnosis. In comparison with the other markers, TPA-M was the most effective of all markers and indicated a positive correlation with the grade of differentiation and nodal status. A remarkable correlation between high levels of TPA-M and CYFRA 21-1 in advanced stages (III, IV) of cancer has been shown., Conclusions: All the tumor markers that were studied have significant limitations in the early diagnosis of cancer, but TPA-M and CYFRA 21-1 may have a role in monitoring the success of therapy and follow up of patients with SCCHN.

This study sought to compare fibrinolytic responses to exercise above lactate threshold (LT) to longer-duration, equicaloric exercise below LT. Fifteen males performed cycle ergometer tests above (77% VO(2)peak) and below LT (41% VO(2)peak) to comparatively evaluate tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) responses. tPA activity significantly (P < 0.05) increased during the >LT test (pre-exercise = 1.57 +/- 0.44 IU ml(-1), post-exercise = 3.85 +/- 4.72 IU ml(-1)), but not the LT (pre-exercise = 8.32 +/- 4.48 ng ml(-1), post-exercise = 14.23 +/- 5.40 ng ml(-1)) and LT test. PAI-1 activity significantly (P < 0.05) decreased during both the >LT (pre-exercise = 15.00 +/- 2.73 AU ml(-1), post-exercise = 10.12 +/- 2.90 AU ml(-1)) and LT test. Our results suggest that exercise

A greater life expectancy has led to an increasing proportion of elderly patients. Increasing age is an important risk factor for cardiovascular disease, but the mechanism of risk is not well understood. Because thrombosis plays a key role in plaque development and the onset of acute coronary syndromes, the age-related increase in cardiovascular risk may be a result of a prothrombotic imbalance. The study aim was to examine the relation between age and thrombotic potential in the Framingham Offspring Cohort. Hemostatic factors previously associated with cardiovascular risk were measured in 3,230 patients (55% women) without evidence of cardiovascular disease who were participating in cycle 5 of the Framingham Offspring Study. The subjects were divided by age into decades. Advancing age was associated with a significant increase in fibrinogen and von Willebrand factor levels and measures of impaired fibrinolytic potential (plasminogen activator inhibitor and tissue plasminogen activator antigens). For men, the mean fibrinogen levels were 21% higher in those > or =70 years versus those aged <40 years (326 vs 268 mg/dl, p <0.001 for linear trend). The mean fibrinogen levels were 15% higher in older than in younger women (330 vs 286 mg/dl, p <0.001). The significant relations persisted after multivariate adjustment. In conclusion, advancing age is associated with elevated levels of hemostatic factors indicative of a prothrombotic state. Because these factors are also associated with endothelial dysfunction, these findings are consistent with an injurious effect of age on the endothelium. Measures to reduce thrombotic potential may be of particular value in the elderly, because they counter the prothrombotic state that develops with aging.

Unlabelled: Tissue polypeptide antigen (TPA) is a serological tumour marker used in the diagnosis, management and follow-up of patients with head and neck cancer. The aim of this study was to evaluate the diagnostic and prognostic significance of pretreatment TPA serum levels in patients with larynx cancer. The predicting ability of this tumour marker with respect to histological type, pathological state and lymph node metastasis was also assessed., Materials and Method: Concentrations of the TPA in the serum from 35 patients were measured by immunoradiometric assay., Results: The results showed the sensitivity value for the group of 35 patients was 29.4%, but in clinical stage IV was 70%. TPA levels correlate with T classification and lymph node metastasis. In T4 tumors it was significantly higher than in T2 (p=0.047). TPA levels were significantly higher in patients with nodal invasion and were generally lower in patients with spinocellular carcinoma (p=0.0048)., Conclusion: Our date indicate that TPA is of limited usefulness in the primary diagnosis in patients with larynx cancer, but is useful in detecting lymph node metastasis.

This cross-sectional study evaluated the relationship of physical fitness, hormone replacement therapy (HRT), and hemostatic profiles at rest and after an acute bout of maximal exercise in 48 healthy postmenopausal women. Subjects were categorized by fitness and HRT user status into four groups: unfit nonusers, fit nonusers, unfit users, and fit users. Fibrinolytic variables tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) activity, and antigen and prothrombin fragment 1 + 2, a molecular marker of in vivo thrombin generation, were measured before and after maximal exercise. Fibrinogen was also measured at rest. Higher tPA and lower PAI-1 activities (P <0.05) were seen in HRT users and fit groups. tPA and PAI-1 antigens were lower in HRT and fit groups (P <0.05) but not after correction for body mass index. Prothrombin fragment 1 + 2 was lower in the fit groups regardless of HRT status (P <0.05). Fibrinogen was similar in all groups. Favorable hemostatic profiles were observed in physically fit compared with unfit women, especially in HRT nonusers. Thus fitness is more strongly related to these hemostatic risk factors compared with HRT since HRT did not affect these hemostatic variables in fit postmenopausal women.

Objective: To evaluate the clinical value of serum tissue polypeptide specific antigen (TPS) for primary hepatic cancer in comparison with alpha-fetoprotein (AFP)., Methods: TPS and AFP were measured by enzyme-linked immunosorbent assay (ELISA) in 85 patients with primary hepatic cancer, 19 with metastatic hepatic cancer, 35 with liver cirrhosis, 22 with chronic hepatitis and 50 healthy control subjects., Results: Serum AFP levels were elevated in patients with hepatocellular carcinoma in comparison with that in cholangiocarcinoma patients (P=0.037), but the difference was not significant (P=0.737). Serum TPS levels were significantly correlated with the tumor size (P=0.001), but not with the number of the tumors, portal invasion, extrahepatic metastasis, clinical stage or histological differentiation (P>0.05). A significant correlation was observed between AFP level and tumor size (P=0.028), portal invasion(P=0.005), and histological differentiation (P=0.000)., Conclusion: TPS alone offers no more clues than AFP for the diagnosis of primary hepatic cancer, though it can be helpful for the diagnosis of cholangiocarcinoma. It has only limited clinical utility as a marker for primary hepatic cancer.

Background: Despite recent progress in the treatment of advanced urothelial cancer, there continues to be a need to identify new active agents and their toxicity spectra. We conducted a study using FOLFOX-4 (oxaliplatin, fluorouracil, folinic acid) in pre-treated advanced bladder cancer patients., Methods: Sixteen eligible patients with advanced disease were treated with oxaliplatin (85 mg/m(3)) on day 1 followed by fluorouracil and folinic acid (De Gramont schedule) on days 1 and 2 every 14 days until disease progression. All patients received nutritional support to increase their caloric intake. Objective responses and toxicity were evaluated. Biochemical responses (reduction of markers) and nutritional parameters (increase in body weight and albumin, and reduction in ferritin and C-reactive protein) were also considered., Results: Three patients obtained an objective response (overall response rate 19%). Hematological toxicity and stomatitis were the most commonly noted side effects, but we observed only low (3-4) grade toxicity. In four patients (25%), we observed a reduction in tumoral markers (carcinoembryonic antigen and tissutal polypeptide antigen) and modified nutritional parameters., Conclusions: Using these doses and schedules of FOLFOX-4 appears to be a promising therapy in patients pre-treated with platinum compounds. More studies are required to assess the possible role of this regimen in the treatment of advanced bladder cancer.

Cytokeratins, belonging to the intermediate filament (IF) protein family, are particularly useful tools in oncology diagnostics. At present, more than 20 different cytokeratins have been identified, of which cytokeratins 8, 18, and 19 are the most abundant in simple epithelial cells. Upon release from proliferating or apoptotic cells, cytokeratins provide useful markers for epithelial malignancies, distinctly reflecting ongoing cell activity. It appears that motifs in certain cytokeratins make them likely substrates for caspase degradation, and their subsequent release occurs during the intermediate events in apoptosis. The clinical value of determining soluble cytokeratin protein fragments in body fluids lies in the early detection of recurrence and the fast assessment of the efficacy of therapy response in epithelial cell carcinomas. The three most applied cytokeratin markers used in the clinic are tissue polypeptide antigen (TPA), tissue polypeptide specific antigen (TPS), and CYFRA 21-1. TPA is a broad spectrum test that measures cytokeratins 8, 18, and 19. TPS and CYFRA 21-1 assays are more specific and measure cytokeratin 18 and cytokeratin 19, respectively. By following patients with repeated testing during management, the oncologist may obtain critical information regarding the growth activity in symptomatic patients. Although their main use is to monitor treatment and evaluate response to therapy, early prognostic information particularly on tumor progression and metastasis formation is also provided for several types of cancers. Cytokeratin tumor markers can accurately predict disease status before conventional methods and offer a simple, noninvasive, cheap, and reliable tool for more efficient management.

The ability of the tumour markers Cancer Antigen 15-3 (CA 15-3), Carcinoembryonic Antigen (CEA), and Tissue Polypeptide Antigen (TPA) to signal progression in breast cancer patients was investigated in this study. Marker interpretation considered the analytical variation, intra-individual biological variation, and the rate of increase. Patient cohorts were as follows: (A) 90 stage II breast cancer patients who were monitored postoperatively, (B) 204 recurrent breast cancer patients who were monitored during first-line chemotherapy, and (C) 112 patients who were monitored during the time period after first-line chemotherapy. The sensitivity for progression was 44% (cohort A), 69% (cohort B), and 68% (cohort C) without any false progression signals. Marker lead-times exceeded 3 months in 20% (cohort A) and 27% (cohort C) of patients. Marker lead-times were 1-6 months among 33% of the patients receiving first-line chemotherapy (cohort B). Trials are necessary to determine whether tumour marker-guided therapy has any prognostic impact. The data suggest that tumour marker information may be used to stop ineffective treatments and reduce unnecessary adverse effects.

Background: Paper deals with detection of the early disease progression in breast cancer patients during follow up using tumor markers., Methods and Results: The basic group of 1184 patients with breast carcinoma in follow up after primary therapy were examined from 1996 to 2002. Sera were tested using commercial kits CA 15-3 (MEIA, Abbot), CEA (IRMA, Immunotech), TPA (IRMA, Byk Sangtec), TPS (IRMA, Beki). Results were compared with the retrospectively confirmed clinical status of individual patients. The authors calculated optimal cut offs and sensitivities and their combinations for particular tumor markers at 95% level of specificity. Best sensitivities for the detection of distant metastases into bone, liver, lung and brain was achieved by CA 15-3 (53-68%). As an optimal combination of tumor markers seems to be the tricombination CA 15-3, CEA and TPA. All the tumor markers have insufficient sensitivity for the metastatic process into the lymphnodes., Conclusions: As optimal combination of tumor markers during the follow up seem to be tricombination CA 15-3, CEA and TPA, but also the clinical relevance and cost effectiveness of these assessments have to be considered. For the tumor disease follow up only CA 15-3 has sufficient sensitivities (at 95% specificities) for the early diagnosis of the metastatic process.

Objective: This study was undertaken to determine whether syncytiotrophoblast microvillous membranes (STBMs) stimulate maternal neutrophils to produce superoxide radicals in women with preeclampsia., Study Design: Serum levels of tissue polypeptide antigen (TPA), which is a marker for STBM, were measured in 25 nulliparous women (10 with mild preeclampsia, 6 with severe preeclampsia, and 9 controls). Superoxide production by maternal neutrophils from cases and controls and by donor neutrophils cocultured with the STBMs from cases and controls was measured spectrophotometrically by reduction of ferricytochrome C., Results: Maternal TPA levels were significantly greater among cases than controls (P=.005). Superoxide production by maternal neutrophils and donor neutrophils cultured with STBM from cases of preeclampsia was greater than controls (P values.006 and.019, respectively), and dose-response relationships were observed. Superoxide production by maternal leukocytes was correlated with superoxide induction by STBMs in culture (P=.007)., Conclusion: STBMs in maternal blood induce neutrophils to generate superoxide radicals that may cause endothelial dysfunction in women with preeclampsia.

Objective: To assess the value of the serum carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and breast cancer-associated antigen CA15.3 (CEA-TPA-CA15.3) tumour marker panel in selecting from a group of patients with equivocal bone scintigraphy, chest X-ray or liver echography, those with skeletal, thoracic or liver metastases. Clinical data of 427 breast cancer patients submitted to an intensive follow-up after mastectomy between January 1986 and December 2000 were retrospectively reviewed., Methods: Among the 427 patients operated on for breast cancer, 221 patients with a total of 332 equivocal instrumental examinations (bone scintigraphy, n = 286; chest X-ray, n = 29; liver echography, n = 17) were reviewed. All 221 patients were followed up clinically, biochemically and instrumentally until there was a clear definition of their condition, metastatic or not, for an average time of 35 months. Positive and negative predictive values of the tumour marker panel in patients with equivocal bone scintigraphy, chest X-ray and liver echography were evaluated; concomitant clinical symptoms were also taken into consideration., Results: Among the 221 patients with equivocal bone scintigraphy, chest X-ray and liver echography, tumour markers showed a positive predictive value of 69, 93 and 83% and a negative predictive value of 98, 86 and 91%, respectively, for the indication of the metastatic or benign origin of the equivocal instrumental imaging. Clinical symptoms were not helpful in predicting metastatic disease (sensitivity, specificity and accuracy of 60, 53 and 54%, respectively)., Conclusions: These data suggest that a short monitoring with the CEA-TPA-CA15.3 tumour marker panel is an important tool to confirm or exclude metastatic disease in those patients who are suspected to have metastases following common instrumental investigations, and it is particularly important to avoid false positive diagnoses., (Copyright 2003 S. Karger AG, Basel)

Objective: To investigate the expression of serum tissue polypeptide-specific antigen (TPS) in breast cancer patients and its clinical value in such cases., Methods: Altogether 160 subjects (90 patients with breast cancer, 40 with benign breast lesions, and 30 healthy subjects) were enrolled in this study. The serum TPS and CA153 levels were measured by ELISA in all the subjects., Results: The levels and positivity rate of serum TPS and CA153 in breast cancer group were significantly higher than those in the normal subjects group and benign lesion group (P<0.01), and became even higher as the malignancy progressed. High serum TPS level was detected in the cancer patients in stage I. Serum TPS level was the most sensitive to bone metastasis of the malignancy, but its highest levels occurred in cases of lymphoid node metastasis (P<0.05). In patients who responded favorably to the treatment, serum TPS and CA153 levels were significantly reduced (P<0.05), but the reduction in TPS levels tended to be more obvious (P<0.05)., Conclusion: Serum TPS can be used as a very useful and sensitive tumor marker in the diagnosis of breast cancer, especially in case of bone metastasis, and may be of great value in clinical decision-making and assessment of therapeutic effect.

Objectives: To evaluate the sensitivity and specificity of serum tissue polypeptide antigen (TPA) as a tumor marker for monitoring tumor recurrence in a prospective Phase II study., Methods: This study consisted of 421 subjects allocated to three groups: 241 patients treated for bladder cancer between 1991 and 1995, 126 subjects with a previous history of bladder tumor but with no recurrence at the time of study enrollment, and 54 healthy volunteers. Soluble TPA concentrations were measured by radioimmunoassay., Results: On the basis of receiver operating characteristic plot analysis, the normal test threshold was set at 63 U/L. For bladder cancer detection, the TPA specificity was 73% and sensitivity was 45%. TPA levels correlated with tumor stage (P <0.01), histologic grade, nodal stage, and metastatic stage and with urinary cytology in univariate analysis. In the subsets of patients with a history of bladder cancer and normal TPA levels, 34.9% experienced a relapse compared with 37.5% of patients with elevated TPA levels (no statistically significant difference). Among the patients with normal TPA levels who experienced recurrence, the mean disease-free interval was 30.6 months compared with 25.1 months in patients with elevated TPA levels (no statistically significant difference). Multivariate analysis showed that TPA was not an independent prognostic biomarker for tumor relapse., Conclusions: In patients with bladder cancer, the TPA serum level correlated with initial tumor stage and grade, but it was not useful for detecting or monitoring relapses.

Study Objectives: We have longstanding experience with tissue polypeptide antigen (TPA), a tumor marker of the cytokeratin (CK) family. In the mid-1990s, a new CK marker, CK 19 fragments (CYFRA 21-1), became popular and widely accepted. This is the first study specifically designed to compare the two markers., Design: Analysis of a single institution database over a 3-year period (ie, 1998 to 2000)., Setting: Community-based hospital and second referral level institution for a province of 500,000 people., Patients: The study included 180 new consecutive patients (143 men) with pathologically documented non-small cell lung cancer (NSCLC), who were observed during and after treatment, and eventually were assessed for status., Interventions: Anthropometric, clinical, and laboratory data, including TPA and CYFRA 21-1 serum levels, were recorded prospectively. Standard nonparametric tests, Kaplan-Meyer survival analyses, Cox proportional hazards models, receiver-operating characteristic (ROC) curves, and estimates were used for statistical analysis., Measurements and Results: A total of 1,299 twin TPA and CYFRA 21-1 serum assays (180 performed at diagnosis and 1,119 performed during or after treatment) were obtained. Intermarker correlation tests revealed incredibly high Spearman rho indexes, ranging from 0.935 at diagnosis to 0.813 to 0.921 at the different follow-up times. The substantial equivalence of the two tests explained all the other results, as follows: their similar profile of correlation with the other variables (objective treatment response: TPA rho, 0.456; CYFRA 21-1 rho, 0.463; follow-up performance status: rho range, 0.424 to 0.435); their superimposable capability to predict important clinical situations (eg, recognizing a metastatic disease at diagnosis with areas under the ROC curve of 0.742 and 0.706, respectively); their nearly identical prognostic significance (the D statistic of the goodness-of-fit of a multivariate survival model: TPA, 851.0; CYFRA 21-1, 851.6)., Conclusions: In most of their traditional clinical applications the two serum tests are equivalent because of their virtual identity. We strongly recommend using a CK test in the evaluation of each NSCLC patient. The choice between TPA and CYFRA 21-1 can be based on nonclinical factors, such as the laboratory experience or preference, and the cost of the two kits.

Many circulating markers are already in clinical practice and in experimental use for the diagnosis, therapeutic monitoring, and in the follow-up of ovarian cancer. The cancer antigen-125 (CA-125) has shown to be useful in epithelial ovarian cancer, but its specificity is too low for the test to be used as a primary screening technique in early stage and particularly in premenopausal women. In the last few years, several studies have focused on using the serial measurement of complementary serum markers to improve the positive predictive value and diagnostic accuracy. The main problem is that the different cellular lines express these markers in a very variable way.

Background: Tissue polypeptide antigen (TPA) is a circulating complex of polypeptide fragments from cytokeratins 8, 18 and 19. It is a tumour-related protein. TPA is an indicator of higher cell proliferation. One function of TP53 is the suppression of apoptosis. TP53 mutations are frequently correlated with tumour development in bladder cancer. One function of TP53 is the suppression of apoptosis. We compared TPA expression and TP53 mutation analysis in tumour-free and bladder cancer patients., Materials and Methods: We examined 93 patients with bladder cancer, 24 patients with benign urological diseases and a control group of 18 healthy individuals. TPA concentration was measured by immunoluminometric assay with LIA-mat TPA-M Prolifigen. The normal cut-off value was defined at 47 U/I for serum and at 60 U/mmol for creatinine. Screening for TP53 mutations in tissue and urine sediment, amplification of the TP53 gene by polymerase chain reaction (PCR) for the exons 5, 6, 7 and 8 and temperature gradient gel electrophoresis (TGGE) were used to analyse the mutations. Statistical analysis included ROC, Mann-Whitney U-Test and Pearson's correlation., Results: For superficial bladder cancer the mutation frequency in TP53 was 44.8%. We found elevated TPA levels in 45.5% in serum and 36.1% in urine. For invasive bladder cancer the mutation frequency in TP53 was 79.2%. Elevated TPA levels were found in 57.7% in serum and in 58.3% in urine. TPA has a sensitivity of 48.9% in serum and 40.4% in urine; the specificity of TPA is 83% in serum and 100% in urine in comparison with healthy individuals. We found no correlation between TPA level and the inflammation status of the patient., Conclusion: This study demonstrated that TP53 mutation frequently occurs in higher stages of bladder tumours. There was no TPA level difference between superficial and invasive bladder cancer. TPA is significantly higher in serum (p = 0.012) and in urine (p = 0.002) in patients with bladder cancer in comparison with control group. TPA in serum is significantly higher in patients with mutation of TP53 (p = 0.046) but not in urine (p = 0.173) in comparison with patients with wild-type TP53.

Impaired fibrinolysis is considered a sensitive marker of endothelial dysfunction. Persistent endothelial dysfunction occurs in some patients following Kawasaki disease. The aim of the present study was to assess whether impaired fibrinolysis is present in long-term survivors of Kawasaki disease. The study included 42 children with a documented history of Kawasaki disease presenting with or without coronary lesions, and 26 healthy controls. Blood samples were collected from patients and controls prior to and following venous occlusion stress testing. Significantly decreased fibrinolytic response to venous occlusion was detected in patients compared with controls due to decreased tissue plasminogen activator. In addition, patients had significantly increased plasma concentrations of plasminogen and fibrinogen, which were related to similar increases of alpha2 -macroglobulin. Decreased fibrinolytic response was found in patients with coronary aneurysms but also in those without coronary lesions. In summary, a decreased fibrinolytic response to venous occlusion may reflect persistent endothelial damage following acute Kawasaki disease, potentially predisposing these patients to accelerated atherosclerosis and cardiovascular disease in early adult life.