Tetranectin Levels Research Articles

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

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

Loss of heterozygosity on the X chromosome is an independent prognostic factor in ovarian carcinoma: from the Danish "MALOVA" Ovarian Carcinoma Study.

Ovarian carcinoma (OC) is the fifth most frequent female cancer type and the fourth most frequent cause of death from cancer among women in Denmark. At the time they are diagnosed with OC, approximately 70% of patients have advanced disease. It is believed that loss of tumor suppressor gene activity plays an important role in the origin and progression of OC and other malignancies. Loss of heterozygosity (LOH) may be detected in individuals heterozygous for an allele and is associated with loss of function of tumor suppressor genes. The polymorphic marker regions (TP53, CACNLB1, D18S58, DXS538, and DXS454) were amplified by polymerase chain reaction followed by separation using gel electrophoresis before LOH was identified. In total, 160 women with primary epithelial OC were included in the study. Univariate analyses showed significant differences in survival between patients who had advanced OC with LOH or with retention using the microsatellite markers DXS454 (P = 0.04) and DXS538 (P = 0.01). Multivariate Cox regression analysis that included all patients showed that DXS454 (relative hazard [RH] = 3.5; P = 0.002; 95% confidence interval [95% CI], 1.6-7.8), radicality of primary surgery (RH = 5.5; P < 0.0001; 95% CI, 2.7-11.1), and serum tetranectin level (RH = 0.8; P = 0.009; 95% CI, 0.7-0.9) were independent prognostic factors for survival. Multivariate Cox regression analysis restricted to patients with International Federation of Obstetrics and Gynecology Stage III-IV disease showed that DXS454 (RH = 3.4; P = 0.007; 95% CI, 1.4-8.1), radicality of primary surgery (RH = 5.4; P < 0.0001; 95% CI, 2.2-12.9), and serum tetranectin level (RH = 0.8; P = 0.042; 95% CI, 0.7-1.0) were independent prognostic factors. LOH at DXS454 (Xq21-q23) appeared to be correlated with reduced survival in patients with OC.

Distribution of HER-2 overexpression in ovarian carcinoma tissue and its prognostic value in patients with ovarian carcinoma: from the Danish MALOVA Ovarian Cancer Study.

The HER-2 (Human Epidermal Growth factor receptor-2, also known as c-erb-2/neu) protooncogene encodes a transmembrane receptor protein, M(r) 185,000. Studies have shown that the HER-2 oncogene is overexpressed in approximately 25-30% of ovarian carcinoma (OC) cases, but to the authors' knowledge, to date no consensus regarding overexpression and prognosis has been possible. The objective of the current study was first to analyze the presence of HER-2 overexpression in tissue from Danish OC patients and correlate the distribution of HER-2 overexpression with clinical and biochemical data and second to investigate the value of HER-2 overexpression as a prognostic marker in OC and to compare this value with the prognostic value of other biochemical markers. The study population was comprised of the first 181 patients diagnosed with epithelial OC who were included in the MALOVA study. The staining procedure for HER-2 overexpression was performed using the p185 antibody. HER-2 overexpression was found in 95 of the 181 investigated cases (52.5%), in which 71 carcinomas (39.2%) were weakly positive (1+) and 24 carcinomas (13.3%) were moderately (2+) to intensely positive (3+). Increased HER-2 expression was found to be correlated with reduced survival. Significant differences in survival between patients with (1+, 2+, and 3+) and those without HER-2 overexpression were found for patients with International Federation of Gynecology and Obstetrics (FIGO) Stage I, Stage III, and Stage III/IV OC (Stage I: P = 0.021; Stage III: P = 0.0078; and Stage III/IV: P = 0.0054). Multivariate survival analyses including all 181 OC patients demonstrated that HER-2 overexpression is a prognostic marker (P = 0.003) together with disease stage, serum tetranectin level, and patient age. For patients with Stage III OC, the only independent prognostic factors detected were HER-2 overexpression (P = 0.009) and serum tetranectin level (P <or= 0.0001). The results of the current study show that HER-2 overexpression has prognostic value both in univariate and multivariate survival analyses. Therefore, the clinical relevance of this observation should be established conclusively by therapy that targets HER-2 in a prospective Phase II clinical trial.

Serum tetranectin is an independent prognostic marker in colorectal cancer and weakly correlated with plasma suPAR, plasma PAI‐1 and serum CEA

Soluble tetranectin (TN) was measured preoperatively in serum from 567 patients with primary colorectal cancer and levels were tested for association with prognosis. The prognostic significance of TN was also compared to that of plasminogen-activator inhibitor-1 (PAI-1), urokinase plasminogen activator (uPAR) and carcinoembryonic antigen (CEA). Significantly shorter survival was found for patients with TN levels below a cut-off point of 7.5 mg/l compared to patients with levels above, as illustrated by Kaplan-Meier curves. By Cox analyses, log TN, log soluble uPAR as well as log CEA were found to have an independent prognostic value for survival (log TN: HR = 0.47, 95% CI: 0.29-0.76); log soluble uPAR: HR = 1.65, 95% CI: 1.18-2.31; log CEA: HR = 1.I1, 95% CI: 1.03-1.20). Based on the multivariate model, a patient with a combination of low levels of TN and PAI-1 and elevated levels of soluble uPAR and CEA had a 2.43 increased risk as compared to a patient with median levels of these biochemical markers. Significant correlations were found with Dukes' stages for all the biochemical markers and between the respective biochemical markers. The findings confirm that TN is a strong prognostic factor in patients with colorectal cancer. TN may be valuable as a prognostic variable in future studies evaluating new treatment strategies for colorectal cancer.

The Prognostic Value of Pretherapeutic Tetranectin and CA-125 in Patients with Relapse of Ovarian Cancer

Objective. The aim of the study was to examine the prognostic values of, respectively, tetranectin (TN) and CA-125 measured in serum from patients presenting with relapse of ovarian cancer (OC).Methods. TN and CA-125 were measured in serum samples from 75 patients with relapse of OC before the start of second-line chemotherapy. The endpoint used was death of OC. The variables were analyzed by univariate life table analysis and multivariate Cox analysis.Results. A significantly shortened survival was found for patients with low serum TN values compared to patients with serum TN levels above one of the cutoff levels. The survivals are illustrated by life tables. No prognostic function was found for CA-125. TN and relapse ≤12 months after primary treatment were the only significant independent prognostic variables among the following variables tested in the Cox analyses: primary and second-line treatment, CA-125, age, histology, performance score, tumor localization, and size.Conclusion. Serum TN determination may be valuable in the selection of patients with relapse of OC for new treatment strategies in future studies.

Predictive values of serum tumour markers tetranectin, OVX1, CASA and CA125 in patients with a pelvic mass

Our objective was to compare the predictive value of the well-established tumour marker CA125 with the newer tumour markers tetranectin (TN), OVX1 and CASA in distinguishing benign and malignant pelvic masses in women. Participants included 185 women, 19 years or older, with a pelvic mass planned for surgical exploration. Significantly different CA125 levels were found between benign tumours and localised ovarian cancer (OC), advanced OC and other non-OCs. Significantly different TN levels were found between benign tumours and advanced OC (stage III/IV), between benign tumours and other cancers and between all OCs and other cancers. For CASA, significant differences were found between benign tumours and all OCs as well as advanced OC. No significant differences could be demonstrated for OVX1. Significant correlations for the 44 OC patients were found between CA125, TN and CASA. No significant correlations were found for OVX1, possibly because of the method used for collection and handling of serum samples. None of the new markers had any additional predictive value compared to CA125. TN and CASA levels correlated with FIGO stage and could be used to discriminate between benign and advanced OC. However, in comparison to the performance of CA125, the additional discriminative value of TN and CASA was minor. Int. J. Cancer 89:519–523, 2000. © 2000 Wiley-Liss, Inc.

Predictive values of serum tumour markers tetranectin, OVX1, CASA and CA125 in patients with a pelvic mass

Our objective was to compare the predictive value of the well-established tumour marker CA125 with the newer tumour markers tetranectin (TN), OVX1 and CASA in distinguishing benign and malignant pelvic masses in women. Participants included 185 women, 19 years or older, with a pelvic mass planned for surgical exploration. Significantly different CA125 levels were found between benign tumours and localised ovarian cancer (OC), advanced OC and other non-OCs. Significantly different TN levels were found between benign tumours and advanced OC (stage III/IV), between benign tumours and other cancers and between all OCs and other cancers. For CASA, significant differences were found between benign tumours and all OCs as well as advanced OC. No significant differences could be demonstrated for OVX1. Significant correlations for the 44 OC patients were found between CA125, TN and CASA. No significant correlations were found for OVX1, possibly because of the method used for collection and handling of serum samples. None of the new markers had any additional predictive value compared to CA125. TN and CASA levels correlated with FIGO stage and could be used to discriminate between benign and advanced OC. However, in comparison to the performance of CA125, the additional discriminative value of TN and CASA was minor.

Serum levels of tetranectin, intercellular adhesion molecule-1 and interleukin-10 in B-chronic lymphocytic leukemia

Background and objective: The fibrinolytic regulator tetranectin (TN), in association with the circulating intercellular adhesive molecule-1 (cICAM-1) and interleukin -10 (IL-10), may be involved in the metastatic cascade of B-chronic lymphocytic leukemia (B-CLL). Our aim was to investigate the potential usefulness of these molecules as prognostic markers in B-CLL. Design and methods: Therefore, TN, cICAM-1, and IL-10 were assessed (ELISA) in the serum of 53 B-CLL patients, classified in Binet A, B, and C stages in comparison with those in 45 healthy subjects (HS). Results: TN was significantly lower in B-CLL patients than in HS (9.63 [8.75–11.51] mg/L, 13.75 [12.56–14.64] ng/mL, respectively, p < 10 −5), being lower ( p = 0.05) in B and C stage patients (subgroup B+C) than in A stage ones (subgroup A). cICAM-1 levels were significantly higher in B-CLL patients than in HS (475.86 [355.86–593.79] ng/mL vs. 225.62 [118.49–312.83] ng/mL, respectively, p < 10 −5) with a tendency for higher levels in subgroup B+C than in subgroup A. A significant correlation of cICAM-1 with lactate dehydrogenase (LDH) ( r s = 0.532, p = 0.049), and a significant increase in cICAM-1 in B-CLL with diffuse bone marrow infiltration (BMI) compared to that in B-CLL with nondiffuse BMI (624.48 [557.24–726.55] ng/mL vs. 480.34 [368.96–590.34] ng/mL, respectively, p = 0.0172) were found. A significant negative correlation between TN and cICAM-1 ( r s = −0.5017, p = 0.0001) was observed. IL-10 was detected in all B-CLL patients and in no HS (7.37 [5.30–10.55] pg/mL), being higher ( p = 0.0153) in C than in A stage patients. A significant correlation of IL-10 with TN and cICAM-1 in subgroup B+C ( r s = −0.659 [ p = 0.014] and r s = 0.679 [ p = 0.011], respectively) was found. Conclusions: The abovementioned findings and good performance characteristics of TN and cICAM-1 in B-CLL suggest the potential usefulness of these adhesive/recognition molecules as prognostic markers in B-CLL. The implication of these molecules along with IL-10 in the disease process deserves further study.

Tetranectin, soluble P-selectin and VCAM-1 in the plasma of children with insulin-dependent diabetes mellitus

Objectives: Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disorder characterized by a variety of haemostatic abnormalities. The purpose of this study was to investigate the levels of tetranectin (TN), a regulator of fibrinolysis, in the plasma of IDDM children in relation to HbA1c levels and to the state of platelet and endothelial cells activation expressed by the levels of circulating P-selectin (cP-selectin) and VCAM-1 (cVCAM-1). Patients and methods: TN, cP-selectin and cVCAM-1 levels were assessed by ELISA in the plasma of 75 uncomplicated IDDM children and compared with those of 33 healthy subjects. Patients were divided into subgroups A and B according to the levels of HbA1c (HbA1c ≤ 6.8% and HbA1c > 6.8% respectively). Results: TN levels have the tendency to be higher in IDDM children [14.98(12.50–18.10) mg/L, P = 0.0210] compared to those in healthy subjects [13.44(10.48–16.32) mg/L] and were significantly higher in subgroup B than in subgroup A [16.92(13.48–18.26) mg/L vs 13.68(11.35–14.89) mg/L respectively, P = 0.0120]. The plasma levels of cP-selectin and cVCAM-1 were significantly elevated in IDDM [301(218–401) ng/ml, P = 0.0004 and 997(814–1222) ng/ml, P = 0.0015 respectively] than in healthy subjects [201(135–243) ng/ml, and 724(602–864) ng/ml respectively]. A trend towards higher cP-selectin levels was observed in subgroup B compared to subgroup A. As regard cVCAM-1, no statistically significant difference was found between subgroups A and B. A significant correlation was found between cP-selectin and cVCAM-1 (r s = 0.32, P = 0.32, P = 0.034), while no correlation was found between these variables and TN or HbA1c. However, a significant correlation was observed between TN and HbA1c (r s = 0.37, P = 0.011) in all IDDM patients. Likewise, a longitudinal follow up of 10 IDDM patients revealed a positive correlation between TN and HbA1c in each patient. Conclusions: These data provide evidence for TN elevation with the increase of HbA1c in uncomplicated IDDM children, suggestive of TN involvement in the haemostatic abnormalities in IDDM. The mechanism by which this would occur is discussed.

Human tetranectin: Methodological and clinical studies

From its discovery in 1986 tetranectin (TN) has been suggested to participate in proteolytic processes through its binding to plasminogen, which enhances the activation of plasminogen to plasmin. Because extracellular proteolysis is an important factor in the ability of malignant cells to infiltrate normal tissues and metastasize, TN was considered to be a potential marker for this proteolysis. We have studied the variations in blood and tissue levels of TN in clinical conditions such as cancer and infection, where increased proteolysis can be expected. Five monoclonal antibodies (MAbs) were produced against human TN, and our study is the first report of stable hybridomas producing MAbs against human TN. All the MAbs reacted with epitopes located within aa-residues 50-181 of the primary sequence. In relative epitope mapping with enzyme immuno assay and isotachophoresis the five MAbs defined two independent epitope groups. Different combinations of MAbs were suitable for enzyme immuno assays and two MAbs could be used for immunohistochemical detection of TN in both fresh frozen and paraffin embedded tissues. The MAbs will facilitate future studies on structure, function, clinical significance and immunolocalization of TN. In primary ovarian cancer neither s/p-TN nor CA 125 were found valuable for diagnosis of localized cancer versus benign tumors. However, s/p-TN combined with CA 125, increased both sensitivity and specificity. S/p-TN should therefore be considered one of the screening markers in conjunction with CA 125, or other comparable markers, in future ovarian cancer screening research studies. Preoperative s-TN was significantly correlated to residual tumor and survival in ovarian cancer patients undergoing second or third look surgery. In conjunction with CA 125 and CASA the predictive value of TN for residual tumor was greatly improved, as the markers were found to supplement each other. If the second look operation had been restricted to patients who had a marker negative test, up to 37% would have avoided surgery. We therefore recommend that these tests are included as potential selection parameters in other studies evaluating second-look surgery. Low p-TN concentration and heavy extracellular staining of TN in the tumors was significantly correlated with a poor prognosis for patients with localized stage I or II or advanced primary ovarian cancer. The prognostic information can be especially valuable for patients with a localized ovarian cancer stage I or II, because about 20% of these patients, believed to be radically operated later present with relapse. We found the p-TN level to be especially useful for patients with localized cancer, indicating that adjuvant chemotherapy may be considered if the p-TN level is low. For patients with advanced primary ovarian cancer and low p-TN the survival was significantly reduced compared to patients with a higher p-TN. The p-TN level was significantly negatively correlated to the extracellular (stromal) staining of TN in the tumors. A heavy stromal TN staining was correlated with a shortened survival and was an independent prognostic factor in the Cox analyses. Patients with advanced primary cancer and a low p-TN, possibly in combination with a heavy stromal staining of TN in the tumors, should tentatively be offered palliative treatment or experimental chemotherapy. Furthermore, patients receiving chemotherapy may be monitored by s/p-TN measurements, as a decrease in TN concentration indicated recurrence 3.6 months prior to clinical diagnosis. A decrease in TN concentration during chemotherapy may therefore indicate change of treatment. Serum TN was a very strong independent prognostic factor of poor treatment response and a shortened survival in patients with metastatic breast cancer. A low pre-chemotherapy s-TN value together with clinical signs of poor treatment response may be an ominous combination, which may suggest change of treatment. For patients with Dukes' stage

Plasma tetranectin levels in patients with unstable and stable angina

Summary It has been recently suggested that the acute exacerbation of chronic inflammatory process accompanied by excessive atheromatous plaque-matrix breakdown may be the crucial link between chronic and acute coronary artery disease (CAD). In the light of this probability, the fibrinolytic regulator, tetranectin (TN) was assessed in the plasma of 43 unstable angina (UA) patients, 35 stable angina (SA) patients, and 34 healthy subjects (HS) in association with selected inflammatory and fibrinolytic markers. Plasma TN levels in patients with UA and SA were significantly lower than those in HS (8.18 (7.08–9.58) mg/L and 10.00 (7.22–10.96) mg/L vs 12.09 (11.78–12.37) mg/L, p −4 ). The sensitivity, specificity and predictive value were 72.1, 97.1 and 97% respectively for UA patients, and 46, 97 and 94% respectively for SA patients. In the 26 (60.5%) of UA patients, which had a complicated in-hospital course, TN levels were significantly lower than those in the 17 (39.5%) uncomplicated UA patients (7.38 (6.77–8.15) mg/L vs 9.67 (8.47–10.84) mg/L, p −4 ). In SA patients the increased levels of C-reactive protein (CRP), fibrinogen (FG), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and D-dimer (DD), in conjunction with the significant positive correlation between CRP and FG, and of both with DD, revealed the existence of a low-grade inflammatory process accompanied by the subclinical activation of reactive fibrinolysis. The substantial increase in the above-mentioned inflammatory and haemostatic markers, along with the significant correlation between the inflammatory markers and DD, as well as between t-PA and DD or FG in UA patients, was consistent with the acceleration of inflammatory and coagulative/fibrinolytic processes. The negative correlation of TN with CRP (r s = −0.707, p −3 ) and FG (r s = −0.664, p −4 ) in UA patients and, to a lesser degree, in SA patients (r s = −0.563, p −3 and r s = −0.457, p = 0.006 respectively) makes possible the involvement of inflammatory components in the regulation of TN in CAD. The negative correlation of TN with DD in SA (r s = −0.356, p = 0.036) and UA (r s = −0.319, p = 0.037) patients along with its superior performance characteristics and predictive correlation with UA clinical outcome in comparison with other inflammatory and fibrinolytic variables studied, suggested its possible implication in the pathophysiologically-important processes associated with atheromatous plaque-matrix breakdown and thrombus dissolution. The significant inverse relation between TN and lipoprotein (a) [Lp(a)] observed in SA (r s = −0.552, p = 0.001) hinted at the common implication of these fibrinolytic regulators in the pathophysiology of chronic CAD. A further investigation of the role played by TN in CAD could perhaps shed light on its significance as a marker of the development of coronary atheromatous lesions and thrombosis.

Tetranectin levels in patients with acute myocardial infarction and their alterations during thrombolytic treatment.

Tetranectin (TN), a new regulator of fibrinolysis, was studied in the plasma of 60 patients with acute myocardial infarction (AMI) and 30 healthy subjects (HS), in relation to D-dimer (DD) and alpha 2-plasmin inhibitor (alpha 2-PI), to investigate its possible involvement in the pathophysiology of AMI. Thirty patients underwent thrombolytic treatment with fibrin-specific plasminogen activator (rt-PA) (group A); the other 30 patients, according to the exclusion criteria, were conventionally treated (group B). Twenty of the thrombolysized patients established early recanalization (subgroup A1), while 10 failed to respond to thrombolytic treatment (subgroup A2). Median (interquartile range), baseline plasma TN levels were lower in AMI patients compared to HS [8.27 (2.75) mg/L versus 12.1 (0.55) mg/L, P < 10(-6)]. In subgroup A1, TN increased at the end of rt-PA infusion and returned to the baseline levels 12 h later. A positive association between DD and TN release (3 h level minus baseline level) was found (rs = 0.48, P = 0.03) in subgroup A1. No significant alterations of TN levels were observed during therapy in subgroup A2 and group B. TN, DD and alpha 2-PI concentrations in group B remained relatively constant during the study period. This study provides evidence of a significant decrease of TN levels in AMI patients compared to healthy subjects and of a remarkable difference in the evolution of TN levels during thrombolytic treatment with rt-PA between recanalized and non-recanalized AMI patients. Thus, an involvement of TN in the formation and dissolution of fibrin clot in AMI patients is worthy of further investigation.

Decreased serum tetranectin in multiple myeloma — relation to disease stage

Summary Tetranectin is a plasma protein which binds to plasminogen kringle-4 and is presumably involved in fibrinolysis. Low levels of serum tetranectin have been described in solid malignancy and related to disease progression. We investigated serum tetranectin in 112 serum samples obtained from 17 patients suffering from multiple myeloma (stage I n=3, stage II n=4, stage III n=10). A sandwich type ELISA was established and validated. Compared to 150 healthy subjects, serum tetranectin was significantly decreased in myeloma patients (9.2 ± 1.6 versus 10.6 ± 1.6 mg/l, p

Use of Tetranectin, CA-125 and Casa to Predict Residual Tumor and Survival at Second- and Third-Look Operations for Ovarian Cancer

Tetranectin (TN), CA-125 and CASA were measured in serum prior to 63 second-look and 5 third-look operations for ovarian cancer. Patients with residual tumor had significantly lower levels of TN and higher levels of CASA and CA-125 compared with tumor-free patients. The predictive values PVPos = 100% and PVNeg = 50.9% were found for TN at 9.3 mg/l. For CASA, a predictive value PVPos = 100% was found at 10 U/ml with a corresponding PVNeg = 52.7%. At the cut-off 35 U/ml for CA-125, the PVPos was 100% and the PVNeg = 53.6%. By combining the markers, PVNeg increased to 61.7% with a PVPos on 100%. Significantly differences in survival were found by lifetable analysis between patients tested as positive and negative respectively for any of the markers. Using multivariate Cox analyses, it was found that every marker had an independent prognostic function for survival.

Tetranectin expression in human colonic neoplasia

The expression of tetranectin in colonic neoplasia was evaluated by determining the tissue distribution by immunohistological analysis of tissue sections and the antigen levels in tissue homogenates and plasma. In normal colonic mucosa tetranectin staining was predominantly found in the goblet cells whereas in adenocarcinomas this staining was confined to the tumour stroma. Colonic adenomas, benign precursors of adenocarcinomas, showed fewer tetranectin positive goblet cells and in some cases showed tetranectin expression in the stroma. Within the tissue homogenates no differences were found in the tetranectin levels between normal mucosa, adenomas and carcinomas. Patients with colonic cancer were found to have significantly decreased plasma tetranectin levels compared to healthy controls. Thus, colonic neoplasia is associated with a change in the tissue distribution of tetranectin, without an obvious change in the tissue level, and a low plasma tetranectin level.

Stability of tetranectin concentration in blood samples

The variabilities of tetranectin in blood due to the use of serum or plasma or due to differences in storage and handling of samples were studied. 57 serum samples collected in 1979 from healthy women were analysed in 1991, the median tetranectin concentration was 10.8mg/l. In a control group from 1991 to 1992 with 178 healthy women, the median serum tetranectin concentration was 10.9mg/l. For 51 plasma samples the median concentration was found to be 9.8mg/l in 1989, 10.2 mg/l in 1991 and 10.0 mg/l in 1992. No differences of tetranectin levels were found in paired samples between plasma and serum, and between hemolyzed and non-hemolyzed samples. Different clotting temperatures and repetitive freezing and thawing were without any effect on the measured tetranectin concentrations. In conclusion, tetranectin levels are the same in plasma and serum, and samples can be handled and stored in different ways without any effect on the tetranectin concentration.

Decreased tetranectin in multiple myeloma

Tetranectin, a recently described human protein widely distributed in the body and with possible importance for cell growth and differentiation, has previously been observed to be decreased in patients with solid malignant tumors. In patients with multiple myeloma, either untreated or previously treated, serum levels were found to be significantly reduced. A negligible interindividual variation was observed. Levels of serum tetranectin were not correlated with serum albumin, hemoglobin, or M-component. Low levels of tetranectin may be related to the growth and spread of malignant cells or reflect a general catabolic state of chronic disease.

Quantitation of Plasma Levels of Tetranectin - Effects of Oral Contraceptives, Pregnancy, Treatment with L-Asparaginase and Liver Cirrhosis

Tetranectin is a tetrameric protein that binds to kringle 4 of plasminogen. Increase of electrophoretic mobility of the otherwise slowly migrating tetranectin in the presence of ethylenediaminetetraacetate was used to develop a reproducible electroimmunoassay to quantify plasma levels. Plasma levels in normals were found within narrow limits of 100 +/- 16 (SD)%, (100% = 0.15 mumol/l). There was no difference between males and females, smokers and non-smokers, and there were no significant changes with age from 20 to 49 years. Patients with severe liver cirrhosis showed a large variation in plasma tetranectin levels but no systematic or average reduction, in contrast to strong reductions in plasma levels of other proteins. Patients treated with L-asparaginase showed a gradual reduction in time in plasma levels of various proteins, though tetranectin showed no significant reduction. It is concluded that tetranectin can be assayed reproducibly in plasma and has a well regulated plasma level. This level is not sensitive to conditions with reductions in synthesis of many proteins, such as during cirrhosis of the liver and during L-asparaginase therapy. The reductions in plasma levels during the use of oral contraceptives and pregnancy indicate involvement of sex steroids in the metabolism of tetranectin.