Panel Of Tumor Markers Research Articles

Detection of carcinomas in an asymptomatic Chinese population: advantage of screening with multiple tumor markers

A total of 73,443 asymptomatic individuals were screened on a voluntary basis for cancer at Chang Gung Memorial Hospital in Taiwan using a panel of tumor markers, including alpha fetoprotein (AFP), CA 125, CA 15-3, CA 19-9, carcinoembryonic antigen (CEA), prostate specific antigen (PSA), chromogranin A (CgA), and squamous cell specific antigen (SCC). The results are derived from data collected from January 1998 to October 2003. A total of 210 cancers (approximately 0.3%) were detected, including cancers of the liver, lung, colon, prostate, stomach, pancreas, breast, cervix, ovary, and bladder. Of the tumor markers monitored, elevated CA 19-9, CEA, and CA 125 were the most frequently detected in a variety of cancers. It was surprising to find that many cancers were not detected by their dominant markers but by the elevation of tumor markers not recommended for monitoring their tumor activity. Screening with multiple circulating tumor markers provides improved sensitivity for cancer detection in asymptomatic individuals before they reach the fatal advanced stage. Screening with multiple tumor markers also allows cancers to be detected in the absence of their dominant markers. If we had not measured the multiple tumor markers, these cancers would have gone undetected.

Prospective Study of a Panel of Tumor Markers as Prognostic Factors in Patients with Squamous Cell Carcinoma of Head and Neck

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. The aim of this study was to investigate the effectiveness of the serum tumor markers CYFRA 21-1, TPA-M, SCCA, and CEA. 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. 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. 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.

Monitoring tumor markers in serial sera predicts disease failure in lung cancer patients following surgery

7040 Background: Patients with early stage non-small cell lung cancer (NSCLC) who undergo resection have a recurrence rate of 50% at 5 years. A contributing factor to such a high recurrence rate is the propensity for early spread of disease, under-staging at the time of resection and the lack of effective monitoring tools. This study investigates the utility of a panel of tumor markers of invasion and metastasis measured in serial sera following surgery to predict early recurrence. Methods: Prospective cohort study of 225 clinical stage I NSCLC patients who underwent resection from January 1996 to December 2000. Serial serum collections were drawn prior to resection and at 1, 4, 6, 12, 18 and 24 months following surgery. Serum protein levels of vascular endothelial growth factor (VEGF), E-selectin, CD44, basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), urokinase plasminogen activator (UPA) and receptor (UPAR) were measured using enzyme-linked immunosorbent assay (ELISA) against a known standard curve. Average monthly change (slope) in each biomarker for each patient, as well as demographic and staging variables, were modeled on recurrence using multiple logistic regression analysis. Cut points in biomarker slope were optimized by c statistic using univariate logistic regression. Results: The median follow-up was 2.7 years, and 87 patients (39%) had recurrent disease. Elevated levels of VEGF and UPAR were associated with increased risk of recurrence, while bFGF was found to be significantly protective after adjusting for stage in multivariable analysis. Conclusions: To date, there have been no studies evaluating the change in the levels of tumor markers collected in serial sera with respect to disease stage, recurrence and cancer-free survival. This study suggests that specific tumor markers collected in serial sera following surgery in patients with NSCLC may serve as a diagnostic tool for detecting early recurrence. No significant financial relationships to disclose.

Evaluation of a Panel of Tumor Markers for Molecular Detection of Circulating Cancer Cells in Women with Suspected Breast Cancer

We examined the feasibility of using molecular characterization of circulating tumor cells as a method for early detection of breast cancer. Women without a prior history of cancer who had a breast abnormality detected on imaging followed by a breast biopsy were enrolled in this study. Density gradient centrifugation and immunomagnetic capture were used to enrich for epithelial cells from approximately 20 mL of blood. Real-time reverse transcription-PCR was used to quantitate the expression levels of the highly breast-specific genes, mammaglobin, gamma-aminobutyric acid type A receptor pi subunit (GABA A(pi)), B305D-C, and B726P in the epithelial cell-enriched samples. The assay was technically feasible in 154 of 199 accrued patients. From their clinical assessment, 100 patients had benign breast disease, 10 patients had ductal carcinoma in situ, and 44 patients had invasive breast cancer. We constructed a diagnostic test that classified patients with mammaglobin levels of at least 32.2 copies/pg beta-actin (units) in their circulating epithelial cells as positive for invasive breast cancer. This resulted in a sensitivity and specificity of 63.3% and 75.0%, respectively. A diagnostic test that classified patients as positive for invasive breast cancer when either mammaglobin levels were >46.3 units or B305D-C levels were >11.6 units increased the sensitivity and specificity to 70.5% and 81.0%, respectively. In the latter test, 12 of the 14 node-positive breast cancer patients were correctly identified. Including GABA A(pi) and B726P in the test did not increase its diagnostic potential. These results suggest that molecular characterization of circulating epithelial cells using mammaglobin and B305D-C offers potential for early detection of invasive breast cancer.

Use of a Panel of Tumor Markers (Carcinoembryonic Antigen, Cancer Antigen 125, Carbohydrate Antigen 15–3, and Cytokeratin 19 Fragments) in Pleural Fluid for the Differential Diagnosis of Benign and Malignant Effusions

The diagnostic value of tumor markers in pleural fluid is subject to debate. The aim of this study was to evaluate the diagnostic performance of several tumor markers in common use for detecting malignant pleural disease. Blinded comparison of four tumor markers in pleural fluid with a confirmatory diagnosis of malignancy by pleural cytology or thoracoscopic biopsy. Two teaching hospitals in Spain. A total of 416 patients (166 with definite malignant effusions, 77 with probable malignant effusions, and 173 with benign effusions) were enrolled. Among them, there were 42 patients recruited from one of the participant centers with thoracoscopic facilities, who had false-negative fluid cytology findings and malignancy confirmed by medical thoracoscopy. Tumor markers in pleural fluid were determined either by electrochemiluminescence immunoassay (carcinoembryonic antigen [CEA], carbohydrate antigen 15-3 [CA 15-3], cytokeratin 19 fragments [CYFRA 21-1]) or microparticle enzyme immunoassay (cancer antigen 125 [CA 125]) technologies. Cutoff points that yielded 100% specificity (ie, all patients with benign effusions had levels below this cutoff) were selected for each marker. Malignant pleural effusions (PEs) had higher levels of pleural fluid markers than did effusions due to benign conditions. At 100% specificity, a pleural CEA > 50 ng/mL, CA 125 > 2,800 U/mL, CA 15-3 > 75 U/mL, and CYFRA 21-1 > 175 ng/mL had 29%, 17%, 30%, and 22% overall sensitivities, respectively. The combination of the four tumor markers reached 54% sensitivity, whereas the combined use of the cytology and the tumor marker panel increased the diagnostic yield of the former by 18% (95% confidence interval, 13 to 23%). More than one third of cytology-negative malignant PEs could be identified by at least one marker of the panel. No single pleural fluid marker seems to be accurate enough as to be introduced in the routine workup of PE diagnosis. However, a tumor marker panel may represent a helpful adjunct to cytology in order to rule in malignancy as a probable diagnosis, thus guiding the selection of patients who might benefit from further invasive procedures.

Diagnostic potential in bladder cancer of a panel of tumor markers (calreticulin, γ‐synuclein, and catechol‐o‐methyltransferase) identified by proteomic analysis

Using proteomic analysis, we previously identified calreticulin (CRT) as a potentially useful urinary marker for bladder cancer. Now, we have also identified gamma -synuclein (SNCG) and a soluble isoform of catechol-o-methyltransferase (s-COMT) as novel candidates for tumor markers in bladder cancer, by means of proteomic analysis. In the process of establishing a superior tumor marker system, we investigated the diagnostic value of a combination assay of these three proteins. Voided urine samples were obtained from 112 bladder cancer and 230 control patients. Urinary CRT, SNCG, and s-COMT were measured as a combined marker by quantitative western blot analysis. Relative concentration of each protein was calculated and the diagnostic value of a concomitant examination of these markers was evaluated by receiver operator characteristic analysis. With the best diagnostic cutoff, the overall sensitivity of the combined markers was 76.8% (95% confidence interval, 69-81%) with a specificity of 77.4% (72-80%), while those of a single use of CRT were 71.4% and 77.8%, respectively. When evaluated in relation to tumor characteristics, such as grade, stage, size, and outcome of urinary cytology, the diagnostic capacity of the combined markers was equal to or better than that of CRT in all categories. Concomitant use of CRT, SNCG, and s-COMT had higher sensitivity for detection of bladder cancer than did single use of CRT. Our study suggests that use of this panel of markers will improve the diagnosis of bladder cancer and may allow the development of a protein microarray assay or multi-channel enzyme-linked immunosorbent assay.

Genetic and Immunophenotype Analyses of TP53 in Bladder Cancer

Altered p53 status is a frequent event in bladder cancer and reported to have prognostic significance. We studied the TP53 gene and its product in 76 patients affected with urinary bladder carcinomas by immunohistochemistry (mAb DO-7), polymerase chain reaction single-strand conformational polymorphism (exons 4-8) followed by direct sequencing of shifted bands, and loss of heterozygosity in 17p (p53CA). H-RAS mutations were also studied. The receiver operating characteristic curve and the logistic-regression analysis were used to evaluate the validity of immunohistochemistry in predicting TP53 mutations. A p53-positive nuclear phenotype was defined by a cutoff of 20% tumor cells being immunoreactive and was found in 23 cases, while TP53 mutations were detected in 22 cases, four of them with a negative p53 phenotype. TP53 deletions were identified in 23 cases. No H-RAS gene mutations were observed. There was a significant association between phenotype and genotype results. Moreover, a significant association was observed between p53 status and tumor stage and grade, being alterations more common in high-stage and high-grade tumors (both chi2 test; P < .01). Deletion of 17p significantly correlated with tumor stage (P < .01) and grade (P = .01), allelic losses being more common in advanced disease. Data from these studies suggest that genetic assays are necessary for the optimal determination of TP53 alterations, mainly in tumors with a p53 negative phenotype, and especially in early stage tumors for which p53 status may assist in determining its progression to invasive disease. Since p53 alterations are significantly associated to clinicopathological features of poor prognosis, the inclusion of both p53 phenotype and TP53 mutation status into a predictive panel of tumor markers for bladder cancer is recommended.

Prognostic stratification of Dukes B colon cancer by a neoglycoprotein

Disease progression of tumors is accompanied by structural changes of the glycan chains of cellular glycoconjugates. Within the concept of the sugar code the presence of complementary receptors such as lectins translates changes in ligand presentation into biological effects, for example in growth regulation and adhesion. By introducing neoglycoproteins to histopathological colon cancer analysis the questions are addressed as to whether specific binding sites for main N- and O-glycan components are present and whether they harbor potential for prognostic predictions. Synthetic conjugation of fucose, lactose, and mannose derivatives to a carrier protein yielded neoglycoproteins for glycohistochemical analysis. The tumor panel included routinely fixed tissue sections from 67 cancer cases (15 Dukes A, 20 Dukes B, 15 Dukes C, and 17 metastatic tumors) and 6 hepatic metastases as well as 20 normal biopsy specimens as control. Quantitative image analysis determined the labeling index and the mean optical density in each case, separating tumor and peritumoral connective tissue. Specific carbohydrate-dependent binding with inter-individual heterogeneity was observed. The distinct staining profiles were not associated with disease stage or metastasis formation. Strong expression of lactose-binding sites in the peritumoral connective tissue especially in terms of the labeling index was significantly correlated with reduced survival in Dukes B patients (p=0.02). A similar tendency was observed in the Dukes C group. In conclusion, the application of the synthetic markers aimed at lectin detection defines lactose binding as new prognostic marker. It has potential relevance for improving the benefit from adjuvant therapy in Dukes B colorectal cancer patients. Technically, chemical ligand immobilization to an inert carrier can find useful application beyond glycosciences in the quest to extend the panel of tumor markers.

Intensive post-operative follow-up of breast cancer patients with tumour markers: Accuracy of serum MCA-CA15.3 and CEA-TPA-CA15.3 tumour marker panels for early detection of relapse

753 Background: In breast cancer serum CEA-TPA-CA15.3 tumour marker panel is a cheap tool with high accuracy for the early detection of relapse (A Nicolini, Br J Cancer 1997); serum MCA and CA15.3 are also reported among the most useful serum tumour markers. However the most suitable cut-off of MCA has not yet been defined. The aims were to compare the MCA-CA15.3 with the CEA-TPA-CA15.3 tumour marker panel and to assess the effect of two different MCA cut-off values on this comparison. Methods: From May 2000 to February 2003, 264 breast cancer patients every 6 or 4 months, according to whether they were at low or high risk of relapse, were monitored with serial serum MCA, CEA, CA15.3, and TPA levels besides history and routine lab examinations. Cut-off value was 4.3 ng/mL (CEA), 32 U/mL (Ca15.3), 95 U/L (TPA), 11 and 16 U/mL (MCA). Tumour marker increase was dynamically evaluated according to a previously described method (A Nicolini, Br J Cancer 2000) Bone scintigraphy, liver echography and chest x-ray...

Role of tumour markers in monitoring and follow-up of colorectal cancer patients

The authors describe the significance of colorectal cancers in public health in Hungary and at international level. This is followed by the discussion of the latest aspects of patients' monitoring and continual follow-up with special emphasis on its clinical significance. In addition to CEA, the most important tumour marker in the present clinical practice, the authors review other tumour markers that might be used in controlling cancer treatment and patients' status. The estimation of treatment effectiveness should be combined with tumour marker level determinations at regular intervals because they are capable of demonstrating the dynamics of malignant processes and, if applied in adequate combinations, indicate the presence of a recurrence or metastasis. The integration of a "tumour marker panel" into the practice of follow-up may help early cancer detection and reduce health care expenses.

Utility of a Serum Tumour Marker Panel in the Post-Operative Follow-Up of Breast Cancer Patients with Equivocal Conventional Radiological Examinations

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.

“Tumour marker guided” salvage treatment prolongs survival of breast cancer patients: final report of a 7-year study

Objectives. – Randomised trials on breast cancer showed no significant benefit from post-operative follow-up with clinical and/or conventional radiological means. We hypothesised that carcinoembryonic antigen (CEA), tissue polipeptyde antigen (TPA), breast cancer associated antigen 115 D8/DF3 (CA15.3) tumour marker panel is sensitive enough for significantly anticipating salvage treatment and prolonging survival of relapsing breast cancer patients. Methods. – From October 1981 to May 1999, 68 (62%) of 109 patients with distant metastases were recruited. Thirty-six (53%) received salvage treatment at the time of significant increase in one or more components of CEA–TPA–CA15.3 tumour marker panel and negative instrumental examinations (“tumour marker guided” treatment) and 32 (47%) were treated only after radiological confirmation of metastases (conventional treatment). The prognostic factors of the two groups did not show any statistically significant difference. Results. – The time from one or more tumour marker increase to clear clinical and/or radiological signs of distant metastases (lead time) was significantly prolonged in the 36 patients with “tumour marker guided” treatment (17.3 ± 13.1 vs. 2.9 ± 2.9 months, P < 0.001, Wilcoxon test) as well as the survival curves from salvage therapy and from mastectomy (the proportion of survivors was: at 36 months from salvage therapy 28% vs. 9%, P = 0.0094; at 84 months from mastectomy 42% vs. 19%, P = 0.0017). The multivariate Cox analysis showed that time from mastectomy to tumour marker increase and “tumour marker guided” salvage treatment were the only significantly different variables ( P = 0.00001 and 0.005, respectively). Conclusion. – These data point out that “tumour marker guided” salvage treatment significantly prolongs disease-free and overall survivals of relapsing responsive patients.

Detection of the Human Organic Anion Transporters SLC21A6 (OATP2) and SLC21A8 (OATP8) in Liver and Hepatocellular Carcinoma

Transport proteins mediating the selective uptake of organic anions into human hepatocytes include the organic anion transporters SLC21A6 (also termed OATP2, OATP-C, or LST-1) and SLC21A8 (OATP8). Both transporters are localized to the basolateral membrane of human hepatocytes. Because of the importance of these transporters for hepatobiliary elimination, including the removal of bilirubin and its conjugates from the blood circulation, we have generated monoclonal antibodies for studies on the expression and localization of these transport proteins. We describe two antibodies, designated monoclonal antibody MDQ (mMDQ) and monoclonal antibody ESL (mESL), directed against the amino terminus and the carboxyl terminus of human SLC21A6, respectively. Both antibodies have been characterized by immunoblot analysis, immunoprecipitation, and immunofluorescence microscopy. While mESL reacted specifically with SLC21A6, mMDQ detects both SLC21A6 and SLC21A8. Neither of the two antibodies reacted with other human, or with dog, rat, or mouse liver SLC21A family members. Antibody mMDQ may be used for the simultaneous detection of SLC21A6 and SLC21A8 in immunoblotting because of its immunoreactivity with both molecules and because of the different molecular masses of both glycosylated proteins in human hepatocytes. This is exemplified in hepatocellular carcinomas where SLC21A6 and SLC21A8 were differentially synthesized and showed an irregular staining pattern. Both transport proteins have not been detected in human hepatoma HepG2 cells. In routine paraffin sections, 10 of 12 hepatocellular carcinomas were focally positive with antibody mMDQ. In contrast, cholangiocarcinomas and liver metastases of colorectal and pancreatic adenocarcinoma were negative without exception. This suggests the usefulness of SLC21A6/SLC21A8 within a panel of tumor markers for hepatocellular carcinomas. Moreover, both antibodies should be useful in studies on the expression and localization of two important uptake transporters of human hepatocytes under physiologic and pathophysiologic conditions.

Fuzzy logic-based tumor marker profiles improved sensitivity of the detection of progression in small-cell lung cancer patients.

Tumor markers were used for disease monitoring in small-cell lung cancer patients. The aim of this study was to improve diagnostic efficiency in the detection of tumor progression in small-cell lung cancer patients by using fuzzy logic modeling in combination with a tumor marker panel (NSE, ProGRP, Tumor M2-PK, CYFRA 21-1, and CEA). Thirty-three consecutive small-cell lung cancer patients were included in a prospective study. The changes in blood levels of tumor markers and their analysis by fuzzy logic modeling were compared with the clinical evaluation of response versus non-response to therapy. Clinical monitoring was performed according to the standard criteria of the WHO. Tumor M2-PK was measured in plasma with an ELISA, all other markers were measured in sera. At 90% specificity, clinically detected tumor progression was found by the best single marker, NSE, in 32% of all cases. A fuzzy logic rule-based system employing a tumor marker panel increased the sensitivity significantly (P>0.0001) in small-cell carcinomas to 67% with the threemarker combination NSE/ProGRP/Tumor M2-PK and to 56% with the best two-marker combination ProGRP/Tumor M2-PK, respectively. An improvement of sensitivity was also observed using the two-marker combination of ProGRP/NSE (sensitivity 49%) or NSE/Tumor M2-PK (sensitivity 52%). The fuzzy classifier was able to detect a higher rate of progression in small-cell lung cancer patients compared with the multiple logistic regression analysis using the marker combination NSE/ProGRP/Tumor M2-PK (sensitivity 44%; AUC=0.76). With the fuzzy logic method and different tumor marker panels (NSE, ProGRP and Tumor M2-PK), a new diagnostic tool for the detection of progression in patients with small-cell lung cancer is available.

New technologies for the identification of markers for early detection of ovarian cancer.

The ovarian cancer screening regimens in current use fail to identify disease at an early curable stage. New technologies are emerging that facilitate the identification of diagnostic tumor markers. In particular, high throughput techniques using microarray technology and proteomic screening have enriched the study of protein expression by ovarian cancer cells. Further evaluation of serum proteins associated with ovarian cancer holds promise for the development of a tumor marker panel that could aid in the early diagnosis of ovarian cancer, and save lives.

The differential diagnostic potential of a panel of tumor markers (CA 125, CA 15-3, and CA 72-4 antigens) in patients with a pelvic mass

Objective: The purpose of this study was to assess the differential diagnostic potential of a combination of CA 125, CA 15-3, and CA 72-4 antigens in the definition of malignant disease, especially ovarian carcinoma in patients with a pelvic mass. Study Design: A total of 412 patients were evaluated in a multicenter, retrospective study. Results: Two hundred twenty-six malignant, 171 benign pelvic tumors (of which 129 were benign ovarian tumors), and 15 borderline tumors were evaluated. One hundred thirty-three patients had ovarian carcinoma. In 76 cases (55%), the International Federation of Gynecology and Obstetrics stage was III or IV. Borderline tumors (n = 15) were excluded from the statistical calculations. CA 125 antigen was the most sensitive marker for ovarian carcinoma (81%). The highest specificity and positive predictive value was obtained with CA 15-3 antigen (95% and 92%, respectively). Considering a concomitant elevation of all 3 markers as positive, a positive predictive value of 97% was found. However, only 28% of the patients in the total group and 41% of the patients with ovarian carcinoma had a concomitant elevation of all 3 markers. The combination of all 3 markers with levels below the cut-off resulted in a (false-positive) positive predictive value for malignancy between 12% and 36%. With the use of logistic regression analysis, we found a correct prediction in 73% of the cases. CA 15-3 antigen makes the most significant (P <.0001) contribution to the logistic model in the prediction of malignancy in the total group, with all pelvic masses with an odds ratio of 3.86. Conclusion: The combination of a simultaneous elevated level of CA 125, CA 15-3, and CA 72-4 antigens was predictive for malignant disease in almost all cases. However, such concomitant elevation was found in few of the malignant masses. Logistic regression analysis revealed that CA 15-3 antigen makes the most significant contribution to a model for the prediction of malignancy in the total group. The logistic model gave a correct prediction in 73% to 83%. The present tumor marker panel seems inferior to combinations with other test modalities, which include ultrasonography and/or physical examination and/or menopausal status or age. (Am J Obstet Gynecol 2002;187:385-92.)

Clinicopathological Analysis of DU-PAN-2 as a Tumor Marker for Endometrial Adenocarcinoma in Comparison with CA19-9.

We investigated the clinical and immunohistochemical availability of DU-PAN-2 (sialyl Lewisc) as a tumor marker for endometrial adenocarcinomas (EMACs) in comparison with that of CA19-9 (sialyl Lewisa). Serum DU-PAN-2 and CA19-9 values of 17 EMACs were measured using an EIA kit and a RIA kit, respectively. The positive/negative cutoff values for both markers were set at the [mean+2×SD] from the serum values of 19 benign uterine cases as follows; DU-PAN-2, 73.9 U/mL; CA19-9, 37.4 U/mL. Immunohistochemical expressions of DU-PAN-2 and CA19-9 in EMACs were analyzed, applying an indirect immunoperoxidase method. The Lewis blood group type was determined using the hemagglutination test. The serum elevations of DU-PAN-2 and CA19-9 higher than the cutoff values before surgery were noted in 29.4% (5/17) and 23.5% (4/17) of EMACs, respectively. Except for one patient who died of systemic tumor dissemination, the elevated serum values of DU-PAN-2 and CA19-9 declined to the levels lower than the cutoff values after surgery. The relationship between immunohistochemical profiles and serum values was statistically proven to be closer in DU-PAN-2 (r=0.609, p=0.0094) than in CA19-9 (r=0.326, p=0.2022). The Lewis negative patients among them were consistently negative for CA19-9 serologically. We believe that DU-PAN-2 could be clinically useful in EMACs as well as immunohistochemically and recommend that this be added into a panel of tumor markers for EMACs.

Primary pulmonary osteosarcoma

Primary pulmonary osteosarcoma is an extremely rare malignancy. To date, only 12 cases have been reported, with a high mortality rate. The authors report on a newly diagnosed patient and describe investigations that were performed using immunohistochemistry and comparative genomic hybridization (CGH). The clinical course of a woman age 37 years is presented. Along with routine histologic examination, immunohistochemistry was used to demonstrate differentiation-associated proteins, oncoproteins, and other markers; CGH analysis for genomic alterations; and histochemistry to demonstrate alkaline phosphatase activity. Immunohistochemical analysis showed varying expression patterns using antibodies against a panel of tumor markers. Most notable was high overexpression of BCL-2 and cyclin D. CGH analysis showed that this neoplasm contained a much higher level of genetic aberrations compared with skeletal osteosarcoma. This tumor exhibited features common to skeletal osteosarcomas but also had some unique features. Genome analysis suggests that this tumor has several genetic aberrations in common with extraskeletal osteosarcoma. The novel regions of instability identified within the tumor genome may contribute toward the unique tumor phenotype and relative chemoresistance.

The prognostic value of tumor markers in patients with glioblastoma multiforme: analysis of 32 patients and review of the literature.

Although several studies have examined brain tumor markers for prognostic value, few investigations have stratified analysis based on specific histologic grade. The objective of this study was to evaluate a single histologic grade of glioma, the grade IV glioma or glioblastoma (World Health Organization Classification), with a comprehensive panel of tumor markers in an attempt to identify those with prognostic significance. Tumor samples from a cohort of patients with glioblastoma multiforme (n = 32) were examined for tumor markers, DNA analysis, and clinical variables in an attempt to determine a 'profile' for this tumor. We used univariate and multivariate statistical analysis to determine the prognostic value of tumor cell ploidy, percent S-phase, DNA index, p53, and Ki-67 labeling index, as well as the variables of gender, race, age, location of tumor, history of chemotherapy, and primary versus recurrent tumor. Two additional tumor markers, multidrug resistance gene 1 and glutathione-S-transferase subtype pi, were included in the sample testing, but were not analyzed statistically. Univariate analysis indicated that increasing age had a strong association with decreased survival. Female gender, increasing Ki-67, no chemotherapy before sample collection, and primary glioblastoma showed some association with decreased survival in the univariate model. The univariate results indicated that race, side of tumor, ploidy, S-phase, DNA index, and p53 had no prognostic value. Multivariate modeling demonstrated that age, gender, and Ki-67 were the strongest factors associated with survival. The relevant literature is reviewed.

The role of tumour markers in improving the accuracy of conventional chest X-ray and liver echography in the post-operative detection of thoracic and liver metastases from breast cancer.

The aim of this retrospective study was to assess the value of a serum tumour marker panel in selecting from among the patients with equivocal chest X-ray (CXR) or liver echography (LE) those with thoracic or liver metastases respectively. Between January 1984 and December 1999, 467 (341 non-relapsed and 126 metastatic) breast cancer patients were followed-up postoperatively. Among the 126 metastatic patients 36 showed thoracic (19 patients) or liver (17 patients) metastases, alone or in conjunction with other organs as the first evidence of distant spread. We focused on this series of 377 patients including 341 non-relapsed plus 36 with liver or thoracic metastases. The patients were followed-up after mastectomy with serial determinations of a panel of CEA-TPA-CA15.3 tumour markers, bone scintigraphy, CXR and LE. Up to December 1999, equivocal CXR occurred in 23 (6.1%) patients of whom 11 (47.8%) developed thoracic metastases; 14 (3.7%) patients showed an equivocal LE of whom 5 developed liver metastases. In the 37 patients with equivocal CXR or equivocal LE prolonged clinical and imaging follow-up over 41 ± 36 months (mean ± SD, range 3–163) was used to ascertain the presence or absence of thoracic or liver metastases. In the 23 patients with equivocal CXR the negative and positive predictive values of the tumour marker panel to predict thoracic metastases were 92% and 100% respectively. In the 14 patients with equivocal LE the negative and positive predictive values of the tumour marker panel for prediction of liver metastases were 90% and 100% respectively. This study shows that in breast cancer patients the CEA-TPA-CA15.3 tumour marker panel has a high value for selecting those patients at high risk of developing clinically evident pulmonary or liver metastases from amongst those subjects with equivocal CXR or equivocal LE. © 2000 Cancer Research Campaign http://www.bjcancer.com