Combination Of Tumor Markers Research Articles

Preoperative CEA and CA 19-9 are prognostic markers for survival after curative resection for ductal adenocarcinoma of the pancreas – A retrospective tumor marker prognostic study

BackgroundThe prognosis for patients with ductal adenocarcinoma of the pancreas (PDAC) remains poor even after curative resection. Carbohydrate antigen 19-9 (CA 19-9) and the carcinoembryonic antigen (CEA) are the most widely used serum-based tumor markers for the diagnosis and follow up of pancreatic cancer. In our analysis we aim to assess the prognostic value of a combination of both tumor markers in patients with pancreatic ductal adenocarcinoma (PDAC). Patients and methodsBetween 01/1995 and 08/2012 we performed a total of 264 pancreatic resections due to PDAC. Patients were stratified into 3 groups in regard to their preoperative tumor marker levels. Survival was compared between the groups using Kaplan Meier analysis and log rank test. Univariate subgroup analysis and multivariate analysis were performed. ResultsFor 259 cases complete follow up could be obtained. In patients with low preoperative CEA and CA 19-9 levels (group 1 n = 91) the mean survival was 33.3 month (CI 95% 25.1–41.5). If one of the analyzed tumor markers (CEA/CA19-9) was preoperatively elevated above the cut-off level (group 2 n = 106) mean survival was 28.5 month (CI 95% 22.1–35.1). 62 patients showed preoperative elevation of both, CEA and CA 19-9 (group 3); mean survival in this group was 23.9 month (CI 95% 13.9–33.9), p > 0.01. Multivariate analysis confirmed preoperative CEA/CA 19-9 level as independent prognostic factor (HR 1.299). ConclusionPreoperative CEA and CA 19-9 levels correlate with patient prognosis after curative pancreatic resection due to PDAC. This is especially true for the most frequently pT 3/4 stages of PDAC. Even if CEA and CA 19-9 might not be appropriate for screening, its serum levels should therefore be determined prior to operation and taken into account when resectability or operability is doubtful.

Diagnostic value of serum tumor markers evaluation for adnexal masses

ObjectiveThe study aim was to investigate the diagnostic value of preoperative serum tumor markers in patients with adnexal masses. Methods. Study included all (358) consecutive patients treated for adnexal tumors at the Clinic of Ob/Gyn, Clinical Center of Serbia in 12 months. Tumor marker levels (Ca 125, CEA, HE 4, Ca 19.9, and Ca 15.3), taken from all women on admission, were compared with postoperative histopathological findings of extracted tumors.ResultsWomen with malignant tumors had the highest levels of Ca 125, CEA, and HE 4 (p<0.01). Mucinous adenocarcinoma produced the highest amounts of Ca 19.9 and CEA. Ca 15.3 was the highest in women with endometrioid carcinoma. There were no significant differences in the levels of all examined tumor markers (p>0.05) between women with benign and borderline tumors. Ca 125, HE 4, and Ca 15.3 can discriminate the malignant from other tumor types well. The highest sensitivity, specificity, positive and negative predictive values (91.04%, 87.6%, 67.9%, 77.2%, respectively) were achieved for the combination of Ca 125 and HE 4.ConclusionsBlood levels of examined tumor markers can be good predictors of the adnexal masses nature. For the most precise evaluation the combination of serum tumor markers should be used.

Operative Management of Cholangiocarcinoma

Cholangiocarcinomas (CCAs) are rare malignancies that originate from the epithelial cells of the bile ducts. It is the second most-common primary liver cancer after hepatocellular carcinoma. Recent epidemiologic studies have shown that the overall incidence and mortality rates of CCAs are increasing. Diagnosis is often challenging due to the difficulty in getting tissue/cytology for confirmation, and it comprises a combination of cross-imaging, tumor markers, histology, and cholangiography. Surgery involving major resections of liver, bile duct, pancreas, and at times adjacent vessels is the only chance for cure. Evaluation should be focused on the assessment of tumor resectability, hepatic reserve, and patient physiological fitness for major surgery. In patients not fit for major surgery, biliary drainage for jaundice is an appropriate intervention and if there is histologic confirmation of a CCA, palliative therapies focused on local and systemic disease control should be considered. The endeavor to expand the indications for liver transplantation reflects the efforts to provide an effective form of therapy for a previously untreatable disease. A multidisciplinary specialized approach should be the platform for providing the best comprehensive care for these patients.

Clinical Usefulness of Serum CYFRA 21-1 in Patients with Colorectal Cancer.

Among diverse tumor markers, pretreatment evaluation and follow-up detection of recurrence in colorectal cancer are generally evaluated by serum carcinoembryonic antigen (CEA) levels. However, there have been some reports about the low accuracy and high false-positive results of CEA in colorectal cancer. We investigated the clinical utilities of CYFRA 21-1 by comparing CEA and cancer antigen 19-9 (CA 19-9) in pretreatment and recurrent colorectal cancer. Using a solid-phase immunoradiometric assay, serum levels of CYFRA 21-1, CEA and CA 19-9 were analyzed in 132 patients with primary colorectal cancer, 124 healthy controls, 104 patients with benign colorectal disease and 19 patients with recurrent colorectal cancer. We determined three different cutoff values to evaluate the sensitivity of diagnostic performance in pretreatment and recurrent colorectal cancer. CYFRA 21-1 (≥ 1.13ng/ml) had a sensitivity of 47%, compared with 37% for CEA (≥ 3.05ng/ml) and 32.6% for CA 19-9 (≥ 23.1ng/ml) in the initial staging of primary colorectal cancer. Using different cutoff values, CYFRA 21-1 showed higher sensitivity for pretreatment colorectal cancer than CEA and CA 19-9 in adenocarcinoma and adenosquamous carcinoma of this study. A mildly significant correlative relationship was noted between Dukes' stages and three tumor markers (p < 0.01). The areas under the receiver operating characteristic curves of CYFRA 21-1, CEA and CA 19-9 were 0.81 ± 0.03, 0.74 ± 0.03 and 0.62 ± 0.04, respectively, for discriminating colorectal cancer patients from patients with benign colorectal disease. In addition, CYFRA 21-1 was determined as the most sensitive tumor marker for evaluating recurrent colorectal cancer for all cutoff values. This study showed that CYFRA 21-1 could be a useful and dependable tumor marker for pretreatment and recurrent colorectal cancer. Further prospective studies on its usefulness with respect to the prognosis and utility of combined tumor markers are needed.

MiRNA‐199a‐3p: A potential circulating diagnostic biomarker for early gastric cancer

Tumor-associated miRNAs have been detected in serum or plasma. We investigated whether plasma miRNA-199a-3p could be a potential circulating biomarker for early gastric cancer (EGC). By using real-time qRT-PCR, the expression of miRNA-199a-3p were compared between these pre-operative plasmas from 30 EGC patients and 70 healthy controls, and between these pre-operative and post-operative plasmas. Further validation was on an independent set of plasmas from 50 EGC patients. The expression of miRNA-199a-3p (47.5 ± 6.5) in plasma in EGC patients was significantly higher than that from healthy controls (13.9 ± 2.7, P < 0.001) and gastric precancerous diseases (GPD) patients (19.2 ± 2.5, P = 0.004), respectively. Furthermore, the expression levels of miRNA-199a-3p (11.8 ± 2.9, P = 0.012) in the post-operative plasmas were significantly reduced when compared to the pre-operative plasmas. With respect of clinicopathological characteristics, the expression of miRNA-199a-3p in plasma was not associated with the depth of tumor invasion. Moreover, the AUC of the expression of miRNA-199a-3p in plasma for EGC diagnosis was 0.818, which was significantly higher than that of combined tumor markers (0.556). The sensitivity, specificity and accuracy of miRNA-199a-3p expression in plasma for EGC diagnosis were 76%, 74%, and 75%, respectively. Plasma miRNA-199a-3p could be a novel potential diagnostic biomarkers for EGC.

Cholangiocarcinoma in a Young Woman With Perinatally Acquired HIV

Cholangiocarcinoma in a Young Woman With Perinatally Acquired HIV

Thymidine kinase 1 as a diagnostic tumor marker is of moderate value in cancer patients: A meta-analysis

Thymidine kinase 1 (TK1) is an enzyme involved in nucleic acid synthesis and is therefore considered to be an important tumor proliferation marker. The aim of the present study was to determine the diagnostic role of TK1 measurement in cancer. An extensive electronic search was performed in PubMed, EMBASE and the Cochrane Library using the keywords 'thymidine kinase 1' and 'tumor' and synonyms. This study was conducted as part of a project to establish evidence-based guidelines for the diagnosis and treatment of cancer. A total of 453 abstracts were screened, after which the full text of 40 studies were selected for further investigation, including screening of the references cited by studies in the original search. Fifteen studies were enrolled following full-text evaluation. The areas under the receiver operating characteristic curves for the radioenzymatic assay (REA), the chemiluminescence immunoassay (CLIA) and the total were 0.88, 0.75 and 0.8, respectively. These results were all between <0.9 and >0.7, which suggested a moderate diagnostic efficacy. The positive likelihood ratio of the CLIA method was the highest (10.229), which demonstrated that CLIA exhibited a satisfactory specificity in tumor diagnosis. However, TK1 as a single diagnostic tumor marker was not of significant value and the combination of more tumor markers in the diagnosis of tumors may be preferable.

Sensitivity of CA 15-3, CEA and serum HER2 in the early detection of recurrence of breast cancer

The aim of this project was to investigate the sensitivity of CA 15-3, CEA and HER2 in the early diagnosis of metastatic breast cancer. Serial serum values of CA 15-3, CEA and HER2 were determined in 107 patients with recurrence after breast cancer. Fifteen of the patients had primary disseminated disease, nine patients only developed local recurrence during the follow-up period and the remaining 83 developed distant metastases. In the group of patients with distant metastatic disease (n=83), elevated serum levels of CA 15-3 (>32.4 U/mL), CEA (>2.5 µg/L for non-smokers and >10 µg/L for smokers) and HER2 (>15 µg/L) were found in 49.4%, 38.6% and 32.5%, respectively, at the time of diagnosis of recurrence. CA 15-3 was significantly better than HER2 (p=0.027). The most sensitive combination was obtained using CA 15-3/CEA (60.2%) or CA 15-3/HER2 (57.8%). Combining all three tumour markers raised the sensitivity to 63.9%. In the subgroup of patients with tissue HER2+ tumours, the sensitivity of HER2 increased to 55.6%. The best combination in this group was CEA/HER2 (66.7%). In the subgroup of patients with tissue HER2- tumours, CA 15-3 was significantly better. The best combination was CA 15-3/HER2 or CA 15-3/CEA with a sensitivity of 55.8% and 59.6%, respectively. The combination of several tumour markers enhances the sensitivity for detection of metastatic breast cancer. We recommend HER2 or the combination of CEA and HER2 in tissue HER2+ and CA 15-3 or the combination of CA 15-3 and CEA in tissue HER2-.

Urinary Tumor Markers Could Predict Survival in Bladder Carcinoma

The early diagnosis of bladder cancer is important for effective treatment of the disease. This study aimed to evaluate the nuclear matrix protein 22 (NMP 22), soluble epithelial cadherin (E-cadherin), cathepthin-D and total protein with clinico-pathological features of bladder cancer, and to determine the relation between each marker and tumor progression after treatment. The study includes 65 patients with bladder cancer, 14 benign urinary diseases and 11 healthy volunteers. Patients were categorized according to bilharzial infestation, T stage, tumor grade, size and the presence of lymph node metastasis. Forty patients were followed for disease progression after surgery. There was a significant increase of NMP22, E-cadherin, cathepthin-D and total protein detected in cancer group compared to healthy and benign groups. It was found that NMP 22 and E-cadherin had highest sensitivity (84.4, 76.9%, respectively) while, total ddedprotein showed highest specificity (77.4%). Tumor size correlated with urinary NMP22 (r=0.3, p=0.02), although, E-cadherin, cathepsin-D and total protein correlated with tumor size (r=0.3, 0.28, 0.2; p=0.01, p=0.01, 0.04, respectively) and lymph node metastasis (r=0.32, 0.34, 0.2; p=0.003, 0.005, 0.04, respectively). Elevated pretreatment urinary NMP22, E-cadherin and total protein levels was associated significantly with bladder cancer recurrence (p=0.02, 0.001, 0.005, respectively). In conclusion, determination of urinary NMP22, E-cadherin and total protein in bladder cancer patients or persons at risk of developing bladder cancer will help in early detection of the disease and prediction of recurrence. The use of a combination of tumor markers is markedly useful than the assessment of single one.

Prognostic significance of a combination of pre- and post-treatment tumor markers for hepatocellular carcinoma curatively treated with hepatectomy

Previous studies reported that the combination of three tumor markers for hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), has the ability to discriminate survival among patients with HCC. In those studies, however, the study population included all patients with various treatment modalities, and tumor markers were measured only before treatment. We investigated the prognostic value of a combination of these tumor markers for HCC, measured before and after treatment, on survival and recurrence in patients treated with hepatectomy. A total of 173 patients who underwent hepatectomy for primary, non-recurrent HCC were analyzed. Tumor characteristics, postoperative survival, and recurrence rates were compared according to the number of elevated tumor markers measured before and after treatment. The correlation between the number of elevated tumor markers before treatment and tumor size, rate of portal vein invasion, and tumor differentiation, respectively, was stronger than that between the number of elevated tumor markers after treatment. In contrast, the number of elevated tumor markers after treatment displayed an excellent ability to discriminate post-treatment survival and recurrence rates compared to that before treatment, and was an independent factor associated with survival and recurrence in multivariate analysis. The combination of tumor markers measured after hepatectomy has a better discriminatory ability for postoperative survival and recurrence in HCC patients treated with hepatectomy in comparison to the combination of tumor markers measured before treatment.

Difficult diagnosis of a primary pancreatic cancer in a young patient with high human chorio-gonadotropin and multiple liver metastases

Aims and background: Authors present a diagnostic controversy in a young male patient (pt) who had cancer of unknown origin with multiple liver metastases, that finally turned to be pancreatic cancer, and also demonstrate a possible connection of an elevated chorio-gonadotropin (hCG) level and pancreatic neoplasm that can emphasise the importance of special combination of tumour markers for an earlier differencial diagnosis, that might lead to favorable survival.

Abstract 3623: Clinical significance of serum tumor markers in patients with esophageal cancer

Abstract Background: Esophageal cancer is still a disease with a high degree of fatality despite resent advances in surgical techniques and various therapies. Several serum tumor markers have been applied to diagnose and to follow-up in patients with esophageal cancer in clinical practice in Japan. The aim of this study was to investigate the diagnostic and prognostic significance of various serum tumor markers in patients with esophageal cancer. Methods: Eighty one patients with esophageal cancer were recruited for this study. Serum level of tumor markers, squamous cell carcinoma antigen(SCC-Ag), p53 antibody(p53-Ab) carcinoembryonic antigen(CEA), and CYFRA 21-1, were measured in subjects before treatment. The results of these tumor markers were compared with the clinicopathological findings of the subjects. Results: The positive rates of SCC-Ag, p53-Ab, CEA and CYFRA 21-1 were 44%, 34%, 17%, and 16% patients with esophageal cancer, respectively. SCC-Ag and p53-Ab showed positive with a relatively high frequency in cases of early stage esophageal cancer or superficial invasion, while CEA and CYFRA 21-1 could rarely be detected in such cases. Positive for SCC-Ag was significantly higher in patients with tumor invading into or through the musclaris propria than the patients within the submucosal layer. Substantially, the positive rate of SCC-Ag was associated with an advanced stage of disease. Values of p53-Ab in serum virtually demonstrated gradual decrease after treatment, not rapid depletion. All negative cases for p53-Ab before treatment showed negative at any point of treatment or follow-up on a consistent basis. CYFRA 21-1 showed positive in cases with distant metastasis. Conclusion: Each tumor marker for esophageal cancer presented different features in a clinicopathological analysis. The use of several combination of serum tumor markers seems to be most important for the detection and follow-up for of esophageal cancer at present. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3623. doi:1538-7445.AM2012-3623

Serological diagnosis of liver metastasis in patients with breast cancer.

ObjectiveTo diagnose and explore the serological diagnostic factors for liver metastasis in patients with breast cancer before symptoms occur.MethodsA total of 430 female in-patients with breast cancer of stages 0 to IIIC who came to Tianjin Medical University Cancer Institute and Hospital from January 2003 to January 2004 were studied and followed up until May 2011. Serum levels of biochemical markers for tumor and liver were measured at the time of diagnosis.ResultsLiver metastasis was more likely to occur in patients with stage III cancer or c-erbB-2-positive expression. Alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase (GGT), alkaline phosphatase, lactate dehydrogenase (LDH), and carbohydrate antigen 153 (CA153) levels were significantly higher in patients with liver metastasis than those without liver metastasis. Diagnostic indices of LDH, GGT, and CA153 were 174 U/L, 32 U/L, and 26.48 µg/L, respectively. The areas under the curves of LDH, GGT, and CEA were 0.795, 0.784, and 0.661, respectively, and sensitivities of parallel tests for LDH and CA153 and for GGT and CA153 were 88.6% and 85.7%, respectively. The specificity of serial tests for both pairs of enzymes was 97.7%.ConclusionsThe sensitivity and specificity of combined tumor and biochemical markers could be used as indicators during screening for breast-liver metastasis.

Detection and clinical significance of DLC1 gene methylation in serum DNA from colorectal cancer patients

Deleted in liver cancer 1 (DLC1) is a new candidate tumor suppressor gene, whose down-regulation or even silence will result from promoter hypermethylation in various human cancers including colorectal cancer (CRC). The aim of this study is toevaluate the diagnostic role of DLC1gene methylationin the serum DNA from CRC patients. This study enrolled 85 CRC patients and 45 patients with benign colorectal diseases. Methylation-specific polymerase chain reaction (MSP) was used to determine the promoter methylation status of DLC1 gene in serum DNA. The combination of DLC1 methylation and conventional tumor markers was further analyzed. Hypermethylation of DLC1 was detected in 42.4% (36/85) of CRC serums, while seldom in the benign controls(8.9%, 4/45) (P<0.001). The aberrant DLC1 methylation in serum DNA was not associated with patients' clinicopathological features and elevated CEA/CA19-9 levels. Furthermore, the combinational analysis of CEA, CA19-9 and DLC1 methylation showed a higher sensitivity and no reduced diagnostic specificity than CEA and CA19-9 combination for CRC diagnosis. The serum DLC1 methylation may be a promising biomarker for the early detection of CRC, which will further increase the diagnostic efficiency in combination with CEA and CA19-9.

Analysis of the RUNX3 gene methylation in serum DNA from esophagus squamous cell carcinoma, gastric and colorectal adenocarcinoma patients.

Human runt-related transcription factor 3 (RUNX3) gene was a new candidate tumor suppressor gene involved in the TGF-β signaling pathway. We evaluated the diagnostic role of RUNX3 gene methylation in serum DNA of esophageal squamous cell carcinoma (ESCC), gastric cancer (GC) and colorectal cancer (CRC) patients. Methylation-specific polymerase chain reaction (MSP) was used to determine the promoter methylation status of RUNX3 gene in serum DNA. The combination of RUNX3 hypermethylation and conventional tumor markers was further analyzed. Hypermethylation of RUNX3 was detected in 51.4% (36/70) of ESCC, 45.2% (28/62) of GC and 41.5% (27/65) of CRC patients, which was significantly higher than that of benign gastrointestinal diseases and healthy donors (p<0.001). Interestingly, aberrant RUNX3 methylation in serum DNA was associated with advanced stage (p=0.027) and lymph metastasis (p=0.032) in ESCC, but not in GC and CRC. Furthermore, the combinational analysis of CEA, CA19-9 and RUNX3 methylation showed a higher sensitivity and no reduced diagnostic specificity than CEA and CA19-9 combination in the three cancers. The serum RUNX3 promoter hypermethylation may be a promising biomarker for the early diagnosis of ESCC, GC and CRC, which was further confirmed by combining with CEA and CA19-9.

Choice of tumour markers in patients with neuroendocrine tumours is dependent on the histological grade. A marker study of Chromogranin A, Neuron specific enolase, Progastrin-releasing peptide and cytokeratin fragments

BackgroundChromogranin A (CgA) is the most important tumour marker for well-differentiated neuroendocrine tumours (NET) and neuron specific enolase (NSE) for poorly differentiated neuroendocrine carcinoma (NEC). This study investigated whether the markers progastrin-releasing peptide (proGRP) and cytokeratin fragments (CKfr) CK8, CK18 and CK19 (MonoTotal®) can be of additional value to the histological classification and help predict survival in these patients. MethodsCgA, NSE, proGRP and CKfr were measured in 242 patients with grade 1 NET (G1NET), 38 with grade 2 NET (G2NET), 42 with large cell NEC (LCNEC), 251 with small cell NEC (SCNEC) and in 282 healthy persons. Results were compared with tumour characteristics and survival by means of Receiver Operating Characteristics (ROC) curves and Cox regression analyses. ResultsThe largest area under the ROC curve was for CgA (0.86, 0.91 and 0.90, respectively) when comparing patients with G1NET, G2NET and LCNEC with healthy persons. ProGRP showed the highest sensitivity (73%) at 95% specificity in patients with SCNEC. In a multivariate survival analysis, only CKfr was associated with survival (P<0.0001) for patients with well-differentiated NET (G1NET and G2NET). For patients with poorly differentiated NEC, both CKfr and NSE were associated with survival (P<0.0001 and P=0.003, respectively). ConclusionWithin all histological groups a combination of tumour markers proved to be more informative as diagnostic and prognostic marker than each marker alone. In patients with well-differentiated NET and LCNEC we recommend the use of CgA and CKfr, whilst in patients with SCNEC, proGRP and CKfr are preferred.

Differentiating Pancreatic Ductal Adenocarcinoma from Pancreatic Serous Cystadenoma, Mucinous Cystadenoma, and a Pseudocyst with Detailed Analysis of Cystic Features on CT Scans: a Preliminary Study

ObjectiveTo determine whether or not detailed cystic feature analysis on CT scans can assist in the differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from serous cystadenoma (SCN), mucinous cystadenoma (MCN), and a pseudocyst.Materials and MethodsThis study received Institutional Review Board approval and informed patient consent was waived. Electronic radiology and pathology databases were searched to identify patients with PDAC (n = 19), SCN (n = 26), MCN (n = 20) and a pseudocyst (n = 23) who underwent pancreatic CT imaging. The number, size, location, and contents of cysts, and the contour of the lesions were reviewed, in addition to the wall thickness, enhancement patterns, and other signs of pancreatic and peripancreatic involvement. Diagnosis was based on lesion resection (n = 82) or on a combination of cytological findings, biochemical markers, and tumor markers (n = 6). Fisher's exact test was used to analyze the results.ResultsA combination of the CT findings including irregular contour, multiple cysts, mural nodes, and localized thickening, had a relatively high sensitivity (74%) and specificity (75%) for differentiating PDAC from SCN, MCN, and pseudocysts (p < 0.05). Other CT findings such as location, greatest dimension, or the presence of calcification were not significantly different.ConclusionThe CT findings for PDAC are non-specific, but perhaps helpful for differentiation. PDAC should be included in the general differential diagnosis of pancreatic cystic neoplasms.

The usefulness of pleural biopsy in benign or malignant pleurisy

Retrospective studies of pleural biopsy, cytology and ADA in pleural effusion were performed in 116 patients with pleural effusion between 1980 and 1988. Pleural malignant disease was diagnosed in 25 patients (75.8%) by cytology, in 19 patients (57.6%) by pleural biopsy. Thus, cytology should be performed first in patients with pleurisy. Both of cytologic study and CEA in pleural effusion were negative in 3 cases of squamous cell carcinoma. Tuberculous pleuritis was diagnosed in 24 patients (50.0%) by pleural biopsy, in 5 patients (10.4%) by isolation of Mycobacterium tuberculosis. Both pleural biopsy and adenosine deaminase activity (ADA) were examined in 19 cases of tuberculous pleuritis and ADA was elevated in 16 patients (84.2%). These data suggested that pleural biopsy was useful for diagnosis of pleuritis and the combination of cytology, tumor markers and ADA with biopsy improved diagnostic rates of pleuritis.

Serological diagnostic factors for liver metastasis in patients with colorectal cancer

To investigate the serological diagnostic factors for liver metastasis in patients with colorectal cancer. One hundred and six adult in-patients with colorectal cancer were studied and divided into patients with liver metastasis (n = 56) and patients without liver metastasis (n = 50). Serum levels of tumor and biochemical markers for liver were measured at the time of diagnosis. The mean survival time was 55.9 mo, 36.8 mo and 68.3 mo for the overall patients, patients with liver metastasis and patients without liver metastasis, respectively. Lactate dehydrogenase (LDH) level was significantly correlated with the survival time of colorectal cancer patients. The levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase (GGT), LDH and carcinoembryonic antigen (CEA) were significantly higher in patients with liver metastasis than in those without liver metastasis. Patients with lymph node metastasis had a higher risk of liver metastasis than those without lymph node metastasis. The cut points of LDH, GGT and CEA for screening liver metastasis were 180 U/L, 30 U/L and 5.0 microg/L, respectively. The sensitivity was 64.3%, 69.6% and 70.4%, and the specificity was 64.0%, 60.0% and 52.4%, respectively. The sensitivity of parallel test was 85.2% for LDH and CEA, and 92.6% for GGT and CEA, respectively. The specificity of serial test was 85.7% for LDH (or GGT) and CEA. Early diagnosis of liver metastasis is of great significance. The sensitivity and specificity of combined tumor and biochemical markers are rather good in screening colorectal liver metastasis.

Detection of Circulation Tumor Cells Using Telomerase-Selective Adenoviral Marker (OBP-401®) in Breast Cancer Patients.

Abstract Background: The detection of circulating tumor cells (CTCs) is a potential method to predict survival of metastatic breast cancer patients as well as outcomes of early breast cancer patients. However, no method for CTCs has yet proven to be the golden standard. We developed a new approach for detecting CTCs using telomerase-specific replication-competent adenovirus expressing green fluorescent protein (GFP) (OBP-401®, Oncolys Biopharma™).Methods: OBP-401® contains the replication cassette, in which the human telomerase reverse transcriptase promoter drives expression of E1 genes, and the GFP gene for monitoring viral replication. This system is consisted of the following steps; (1) virus-infection for 7.5 ml whole blood (incubated with 4 X 108 Plaque Forming Unit OBP-401 virus for 24 hours at 37 Celsius), (2) dead cell staining using L23102 (invitrogen™), (3) virus-inactivation and RBC elimination, and (4) detection of GFP expressing cells using fluorescence microscopy. In a preclinical study, the sensitivity of this system was assessed using cell lines. Next, we conducted feasibility studies for CTCs detection in 80 healthy individuals, 50 metastatic, and 27 early breast cancer patients. In metastatic and early breast cancer patients, we compared the sensitivity of this system with that of CellSearch® (Veridex™) and tumor makers (CEA and CA15-3). GFP-positive cells (viable CTCs) and L23102 expressing cells measuring ≥ 20µm in diameter (dead CTCs) were considered as CTCs in this system.Results: The sensitivity of this system, which was determined by a serial dilution of MDA-MB-468 cells against healthy volunteer's blood, was 1 cell per 7.5 ml. No CTCs were detected in any of healthy controls. Of 50 metastatic patients, 12% were primary breast cancers with stage IV disease, 24% were in the 1st line chemotherapy setting, and 42% were heavily pretreated with chemotherapy. The sensitivities of tumor markers, CellSearch®, and OBP-401® were 78%, 54%, and 66%, respectively. Neither CTCs detected with CellSearch® nor OBP-401® were significantly associated with clinicopathologic parameters. However, CTCs-positivity detected with CellSearch® were strongly associated with CA15-3 positivity (p = 0.003). Of 14 patients with normal CA15-3 levels, CellSearch® detected CTCs in three patients (21%) but OBP-401® in nine patients (64%). The sensitivity of the combination of tumor markers and OBP-401® was 92%. In 27 early breast cancers (Stage1 7, StageII 17, StageIII 3), three patients were treated with neoadjuvant chemotherapy (NAC). All blood samples were drawn before surgery or NAC. The sensitivities of tumor markers, CellSearch®, and OBP-401® were 7%, 0%, 67%, respectively. There were no significant correlations between CTCs detected with OBP-401® and clinicopathologic features.Conclusion: OBP-401® showed no false positive in healthy controls, and a high sensitivity for CTCs detection, particular in metastatic breast cancer patients with normal 15-3 levels and early breast cancer patients, compared with CellSearch®. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3012.