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Results for “Biomarker variability”

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PubMed1992

Protein adsorption of biomedical polymers influences activated monocytes to produce fibroblast stimulating factors.

The studies presented in this manuscript were based upon the hypothesis that monocytes/macrophages selectively produce cytokines and growth factors due to their interactions with polymers and proteins which are adsorbed to their surfaces. These factors in turn selectively influence the ability of fibroblasts to proliferate. The factors which influence fibroblast proliferation were released from monocytes incubated with polymers: Biomer, polydimethylsiloxane (PDMS), polyethylene (PE), expanded polytetrafluoroethylene (ePTFE), Dacron, and control polystyrene with and without preadsorption with physiological concentrations of IgG, fibrinogen, fibronectin, hemoglobin, or albumin. No simple correlation was found between adsorbed protein, biomedical polymer, and the ability of monocytes to produce growth factors and cytokines which influence fibroblast proliferation. This is evidence for selective protein-polymer interactions which in turn selectively activate monocytes to produce variable cell cycle competence and progression factors controlling fibroblast growth.

Adsorption↗

PubMed1999

Expression of nm23-H1 in colorectal cancer: no association with metastases, histological stage, or survival.

The correlations of nm23-H1 expression in primary cancer lesions with the already confirmed 14 prognostic variables and survival were examined in 52 advanced colorectal cancer patients, because the clinical roles of nm23-H1 expression in the cancer lesions remain controversial. An immunohistochemical expression of nm23-H1 was found in 23 lesions (positive group) but not found in 29 lesions (negative group). No significant difference between the positive and negative groups was found according to 12 clinicopathological variables including vascular invasion, lymph node and liver metastases, and histological stage. The carcinoembryonic antigen levels (21.5+/-33.4 ng/ml) of the draining venous blood and argyrophilic nucleolar organizer regions score (3.35+/-1.36 per nucleus) of the cancer cells in the positive group were not significantly diffeent from those (34.1+/-102.9 ng/ml and 3.32+/-1.00 per nucleus, respectively) in the negative group. In addition, no significant difference was found in the survival curves or the 5-year survival rates of the positive and negative groups. From these results, it may be concluded that the nm23-H1 expression was not associated with the aforementioned prognostic variables and the prognosis of advanced colorectal cancer patients.

Aged↗

PubMedDate not supplied

Lipid profile, haemostatic variables and angiographically-defined coronary artery disease: a cross-sectional study in an Irish population.

More than 300 risk factors for coronary artery disease (CAD) have been described. There are important geographical and racial differences in both the prevalence of CAD and of potential risk factors. The purpose of this study was to determine the relationship between both the presence and extent of angiographically defined CAD in an Irish population and a spectrum of clinical risk factors, lipid profile and haemostatic variables. On univariate analysis, age, male gender, history of smoking, history of hypertension, total cholesterol, triglycerides, LDL, Cholesterol, the LDL:HDL ratio, apoprotein B-100 and the apoprotein B-100: A-II ratio were associated with the presence of CAD. However, in multivariate analysis only age, male gender, a history of smoking and the apoprotein B-100: A-II ratio remained significantly associated with the presence of CAD. These same risk factors and apoprotein B-100 were significantly associated with the extent of CAD on multivariate analysis. In addition, apoprotein B-100 levels appeared to be associated with disease extent. When all significant variables associated with the presence or extent of CAD were analysed together in a multivariate model, they only accounted for 28% of the variability in the distribution of CAD. Thus, advancing age, male gender, cigarette smoking and apoprotein B-100 appear to be important correlates of the presence and extent of CAD in this selected population. However, in individual patients most of the variability in the distribution of occlusive CAD remains unexplained.

Adult↗

PubMed1996

MHPG and heart rate as correlates of nonresponse to drug therapy in panic disorder patients. A preliminary report.

Little is known about biological predictors of treatment response in panic disorder (PD). In the present study heart rate, blood pressure, plasma cortisol and plasma MHPG were investigated at baseline in a sample of 44 PD patients as possible predictors for nonresponse to treatment. We used a strict definition of nonresponse to find patients who did not respond at all after 12 weeks of treatment with brofaromine or fluvoxamine. Patients were considered nonresponders when they fulfilled two criteria: they did not show a 50% reduction of agoraphobic avoidance and they still experienced panic attacks at endpoint. The variables that differed significantly between the groups were used to predict nonresponse to drug therapy. Using this strict definition of nonresponse, 15 patients (32.6%) were considered nonresponders. These patients were characterised by a higher plasma MHPG concentration and a higher heart rate at baseline. These variables were subsequently used to predict nonresponse.

Adult↗

PubMed2005

C-reactive protein levels in patients on maintenance hemodialysis: reliability and reflection on the utility of single measurements.

BACKGROUND: Single C-reactive protein (CRP) values have been associated with death and cardiovascular disease in dialysis patients. We prospectively obtained multiple CRP values in stable patients, hypothesizing that values would remain stable in the absence of disease and that a single CRP value would be a reliable marker of risk. METHODS: Four CRP values per week for three consecutive weeks were obtained in 10 clinically stable patients receiving conventional HD. Using prespecified cutoffs of 2.2 and 4.4 mg/l, the frequency of risk misclassification relative to the lowest CRP value obtained was determined. Within and between patient variability was also calculated. RESULTS: The median age was 54 years, and the average duration of dialysis was 41 months. Nine out of ten patients had at least one abnormal CRP value (>2.2 mg/l), six had all values elevated, and seven had an abnormal median CRP. The overall coefficient of reliability was 0.63 (95% CI 0.42-0.87). The misclassification rate varied with cutoff, and ranged from 0-83% and 0-58% using upper limit of normal (ULN) and twice ULN, respectively. The within patient variability was 0.37 for the entire cohort, and 0.33 when three patients with intercurrent acute inflammation were excluded. CONCLUSIONS: CRP exhibits short term variability in HD patients, resulting in a risk of misclassification depending on sampling time and chosen cutoff point. Single CRP values must be interpreted with caution, and multiple measurements, or use of other biomarkers, should be considered.

Aged↗

PubMed2004

Evidence of association of the CYP2E1 genetic polymorphism with micronuclei frequency in human peripheral blood.

Micronuclei (MN) are used as one of the cytogenetic biomarkers, and intra- and inter-individual variations in this frequency have been reported in human blood lymphocytes. Polymorphisms in a few metabolic enzyme genes seem to account for a proportion of this variability, but the impacts of specific genetic variants on the MN frequency have not yet been clarified. Here, we investigated the relationship between the MN frequency and several gene polymorphisms in 90 healthy Japanese men. The subjects with the CYP2E1(*)3 variant allele had a statistically lower mean MN frequency than subjects with the CYP2E1(*)1/(*)1 wild type. Furthermore, the adjusted odds ratio (OR) of the CYP2E1(*)3 variant with higher MN frequency levels was also significantly lower and calculated to be 0.25 (95% CI 0.07-0.83), when the OR for the subjects with the CYP2E1(*)1/(*)1 wild type was defined as 1.00. These data suggest that the CYP2E1(*)3 polymorphism may have the potential to influence the baseline frequency of MN.

Adult↗

PubMed2006

Intranuclear immunolocalization of 14-3-3 protein isoforms in brains with spinocerebellar ataxia type 1.

Immunolocalization of 14-3-3 protein isoforms, one of the interacters with ataxin 1, was investigated in spinocerebellar ataxia type 1 (SCA 1) brains using isoform-specific antibodies. Samples from the pons and from the cerebellum of four SCA1 cases and three controls were studied. The intensity of the immunoreactivity (IR) and its subcellular topography were analyzed. In control subjects, granular immunoreactivity for an epitope common to all known isoforms of 14-3-3 proteins (14-3-3 COM) found in the cytoplasm of some pontine and dentate nucleus neurons was weak. It was observed in some Purkinje cells, while its intensity varied. Many nuclei of those neurons and Purkinje cells of SCA1 were intensely immunopositive for 14-3-3 COM, while it was less in their cytoplasm. Expanded polyglutamine epitope was colocalized to 14-3-3 COM epitope in some pontine neurons, sometimes accumulated in intranuclear inclusion-like structures. This findings support previous reports that 14-3-3 proteins stabilize mutant ataxin 1 in nucleus and possibly lead to neurodegeneration. However, nuclear localization of 14-3-3 proteins in SCA1 brains was dependent on its isoforms, i.e. pontine neurons intensely positive for beta, Purkinje cells for tau and dentate nucleus neurons for both, while all of those neurons were consistently positive for zeta isoform, although sigma isoform tended to be located in the cytoplasm. Nuclear accumulation and isoform- and region-dependent subcellular localizations of 14-3-3 proteins may be related to SCA1 pathology, which exhibits marked regional variability.

14-3-3 Proteins↗

PubMed2002

Post-stress recovery of pituitary-adrenal hormones and glucose, but not the response during exposure to the stressor, is a marker of stress intensity in highly stressful situations.

Acute immobilization in male rats elicited the same ACTH, corticosterone and glucose response as foot shock when measured immediately after stress. However, post-stress recovery of plasma ACTH, corticosterone and glucose levels were delayed in immobilized versus shocked rats. Similarly, stress-induced anorexia was much greater in the former animals. All these data suggest that post-stress speed of recovery of some physiological variables is positively related to stressor intensity and could be used to evaluate it.

Adrenocorticotropic Hormone↗

PubMed2002

Expression of p53 protein and tumor angiogenesis as prognostic factors in nasopharyngeal carcinoma patients.

The objective of this study was to evaluate the possible prognostic significance of p53 protein overexpression and tumor angiogenesis (TA) in nasopharyngeal carcinoma (NPC) patients, together with other clinicopathological variables. Forty-two NPC patients were evaluated in relation to survival. Nuclear p53 overexpression in neoplastic and endothelial cells was detected by immunohistochemistry (IHC) with the monoclonal antibody DO-7 and the polyclonal antibody against factor VIII-related antigen, respectively. Thereafter, we evaluated p53 cases in order to determine their nuclear immunoreactivity from negative (-) to positive (+, ++, +++). In addition, microvessels were counted in the most active areas of tumor neovascularization or hotspots using an image computer analyzer (MicroImage). A Cox multiple regression survival analysis was used to determine the best prognostic indicators in NPC patients. As a result, tumor microvessel count, considered as a continuous variable, was the most important independent prognostic indicator in relation to survival (p = 0.0273), with a relative risk of death of 2,4399 [95% confidence interval = 1.1051 ; 5.3871] associated with the highest microvessel counts. Moreover, the only clinicopathological variable that demonstrated prognostic value in a Cox multiple regression survival analysis was histological type (p = 0.05). In addition, we did not observe any statistical association between intratumoral microvessel density (IMD), clinicopathological variables and p53 protein expression.

Biomarkers, Tumor↗

PubMed2005

Comparative biochemical analyses of venous blood and peritoneal fluid from horses with colic using a portable analyser and an in-house analyser.

Fifty-six horses with colic were examined over a period of three months. The concentrations of glucose, lactate, sodium, potassium and chloride, and the pH of samples of blood and peritoneal fluid, were determined with a portable clinical analyser and with an in-house analyser and the results were compared. Compared with the in-house analyser, the portable analyser gave higher pH values for blood and peritoneal fluid with greater variability in the alkaline range, and lower pH values in the acidic range, lower concentrations of glucose in the range below 8.3 mmol/l, and lower concentrations of lactate in venous blood in the range below 5 mmol/l and in peritoneal fluid in the range below 2 mmol/l, with less variability. On average, the portable analyser underestimated the concentrations of lactate and glucose in peritoneal fluid in comparison with the in-house analyser. Its measurements of the concentrations of sodium and chloride in peritoneal fluid had a higher bias and were more variable than the measurements in venous blood, and its measurements of potassium in venous blood and peritoneal fluid had a smaller bias and less variability than the measurements made with the in-house analyser.

Animals↗

PubMed2003

Increased risk of falls and increased bone resorption in elderly men with partial androgen deficiency: the MINOS study.

The goal of this study was to identify the clinical and biological patterns of hypogonadism in a cohort of 1040 elderly men. Residual androgenic activity was estimated by total testosterone as well as the apparent free testosterone concentration (AFTC) and free testosterone index (FTI) calculated on the basis of concentrations of SHBG and total testosterone using appropriate formulae. The lower limit of the normal range defined by 2 SD below the mean in 150 healthy, nonobese, and nonsmoking men, aged 19-40 yr, was calculated for total testosterone (9.26 nmol/liter), AFTC (146 pmol/liter), and FTI (0.14 nmol/nmol). The prevalence of hypogonadism increased with ageing. Hypogonadal men were older and heavier (due to a higher fat body mass) and had lower concentrations of 17 beta-estradiol and androstenedione than men with normal androgenic activity. Men with decreased AFTC had a slightly lower bone mineral density (BMD) at certain sites. Men with decreased FTI had lower appendicular skeletal muscle mass and relative skeletal muscle index. For all three measures of androgenic activity, hypogonadal men had increased levels of the markers of bone resorption. In the multiple regression models including both 17 beta-estradiol and testosterone (total, AFTC, or FTI), 17 beta-estradiol was the only significant determinant of BMD. In the multiple regression models including 17 beta-estradiol and AFTC or FTI, only testosterone was a significant determinant of the variability in bone formation markers, whereas both 17 beta-estradiol and testosterone were significant determinants of the variability of the markers of bone resorption. Hypogonadism was associated with an increase in the risk of falls, an impairment of static and dynamic balance, as well as the inability to stand up from a chair and to perform the tandem walk. Decreased AFTC (<146 pmol/liter) discriminated best men with functional disabilities (odds ratio, 1.54-7.95; P < 0.05-0.0001). Hypogonadal elderly men had increased bone resorption that was not adequately matched by an increase in bone formation, lower muscle strength, impaired static and dynamic balance, a higher risk of falls, and, in men with low AFTC, a slightly lower BMD. Low AFTC seems to have the best discriminative power for densitometric, biochemical, and functional parameters, followed by FTI, whereas total testosterone was the least discriminative. In multiple regression models, 17 beta-estradiol was the strongest determinant of BMD, and AFTC and FTI were significant determinants of the variability in bone formation markers, whereas both 17 beta-estradiol and testosterone determined the variability in bone resorption markers.

Accidental Falls↗

PubMed2006

Analysis of the risk factors for incidental carcinoma of the prostate in patients with benign prostatic hyperplasia.

PURPOSE: To determine the occurrence of incidental carcinoma of the prostate, its characteristics, and the risk factors for this diagnosis in a group of patients surgically treated for benign prostatic hyperplasia. METHODS: The study comprised a retrospective analysis of 218 patients. After surgical treatment, patients with the finding of incidental carcinoma of the prostate were compared to those without this finding. The preoperative variables analyzed were patient age, digital rectal examination, PSA, PSA density, prostate volume, and preoperative prostate biopsy. We also determined the sensitivity, specificity, positive predictive value, and negative predictive value of digital rectal examination and PSA for the finding of incidental carcinoma of the prostate at surgical specimen analysis. RESULTS: Thirteen (6.2%) out of the 218 patients presented incidental carcinoma of the prostate. Eight (61.5%) of these tumors were classified as T1a and 5 (38.5%) as T1b. Only advanced age (P = 0.003) and the presence of a suspect digital rectal examination (P = 0. 016) were statistically related to the findings of the surgical specimen analysis. The sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of incidental carcinoma were 23.0%, 96.6%, 30.0%, and 95.2% for a suspect digital rectal examination and 85.0%, 34.1%, 7.5%, and 97.2% for a PSA greater than 4.0 ng/mL. The accuracy for these methods was 92.2% and 37.1%, respectively. CONCLUSIONS: Advanced age and the presence of a suspect digital rectal examination represent the most important risk factors for the diagnosis of an incidental carcinoma of the prostate. However, the low positive predictive values reflect the weak correlations among these variables.

Age Factors↗

PubMed2005

Immunohistochemical expression of beta-catenin in solitary fibrous tumors.

CONTEXT: Immunohistochemical staining for beta-catenin may be used as an indicator of the integrity of the Wnt signaling and beta-catenin degradation pathways. Among mesenchymal tumors, aberrant nuclear localization of beta-catenin is seen in desmoid-type fibromatoses but has not been described for solitary fibrous tumors that may mimic the former lesions, especially in small biopsy samples. OBJECTIVE: To study the immunohistochemical expression of beta-catenin in solitary fibrous tumors. DESIGN: We performed immunohistochemical staining for beta-catenin in 12 solitary fibrous tumors, one of which showed histologic features of malignancy. RESULTS: All the tumors showed strong and diffuse reactivity for beta-catenin. Four tumors (33%) showed nuclear staining for beta-catenin, whereas the remaining tumors showed either a membranous or mixed membranous and cytoplasmic pattern of staining. The only histologically malignant tumor of the group showed a mixed membranous and cytoplasmic pattern of staining for beta-catenin. CONCLUSIONS: Immunohistochemical staining for beta-catenin in solitary fibrous tumors does not show a consistent pattern, which may be due to differences in tumorigenesis. Larger studies with clinical follow-up are required for estimating the impact of the variable staining pattern on clinical behavior of these tumors.

Adult↗

PubMed2005

Prediction of mortality in rheumatoid arthritis based on disease activity markers.

OBJECTIVE: The risks and predictors for mortality in patients with rheumatoid arthritis (RA) were examined in a cohort of 152 consecutive outpatients (119 women, 33 men) seen in a 2 month period. METHODS: We evaluated 4 measures of disease activity: erythrocyte sedimentation rate (ESR), physician and patient global assessment of disease activity, and the Ritchie Articular Index (RAI) as mortality predictors, adjusting for disease severity, treatment, and cardiovascular disease (CVD) comorbidity. RESULTS: During followup from 1978 through 1998, 111 patients (86 women, 25 men) died, and only one was lost to followup. The standardized mortality ratio for women was 161 (95% confidence interval 129-199), for men 152 (95% CI 99-223), and for both sexes combined 156 (95% CI 128-188). In a proportional hazards model adjusted for age and sex, at the beginning of the period and for the whole group, significant predictors of mortality were Steinbrocker functional class, Larsen index, CVD comorbidity, use of corticosteroids ever, ESR, and the physician and patient global assessment of disease activity; but the rheumatoid factor (RF), RAI, and use of disease modifying antirheumatic drugs were not significant predictors. When evaluating the 4 assessments of disease activity adjusting for confounders, only physician global assessment hazard ratio (HR) = 1.32 per 1 SD (95% CI 1.00-1.74) and ESR HR = 1.47 per 1 SD (95% CI 1.11-1.93) were significant predictors. CONCLUSION: This longterm followup study of a single clinical patient cohort showed a significant increase in mortality among patients with RA compared to the general population in Malmö. In addition to disease damage and CVD comorbidity, measures of disease activity independently predicted mortality, which supports the hypothesis that improving these variables may also improve longterm outcome.

Adult↗

PubMed1994

Fibrinogen, D-dimer and thrombin-antithrombin complexes in a random population sample: relationships with other cardiovascular risk factors.

Fibrinogen is an independent risk factor for cardiovascular disease and both D-Dimer and Thrombin-Antithrombin complexes may be suitable as laboratory markers of deep venous thrombosis and are becoming more widespread in clinical practice. The aim of our study was to evaluate their normal range and to examine their correlation with various cardiovascular risk factors. Fibrinogen, D-Dimer and Thrombin-Antithrombin complexes were assessed in 516 normal subjects randomly selected from the National Health Service register of Trieste (Italy). In our community the mean value of fibrinogen was 283 +/- 71 mg/dl. Fibrinogen increases with age in males and was significantly higher in male smokers. In non-smokers, females had significantly higher fibrinogen values than males. The mean value of D-Dimer was 306 +/- 130 ng/ml. In females it is significantly higher. The fibrinogen and D-Dimer correlation coefficient was 0.20 (p < 0.001). The mean level of Thrombin-Antithrombin complexes was 6.25 +/- 6.8 ng/ml with a distribution markedly skewed towards the left; males had lower concentration than females (p = 0.047). Multiple regression analysis for fibrinogen as a dependent variable showed that D-Dimer, LDL-cholesterol, Body-Mass Index and Thrombin-Antithrombin complexes were poor predictors for fibrinogen plasma levels (R2 = 0.23) and that fibrinogen, ApoA1 and age can explain only about 10% of the observed variability in D-Dimer.

Adult↗

PubMed1997

Factors affecting various biomarkers in untreated lung cancer patients and healthy donors.

The purpose of the present communication was to determine in lung cancer patients and healthy donors if there was a possible association between cancer and biomarkers of cytogenetic damage and ras p21 oncoprotein levels, and if various exogenous confounding factors (such as smoking habit) and endogenous ones (age, sex, etc.) could affect these biomarkers. Peripheral blood and plasma were collected from 31 lung cancer patients prior to treatment and 35 healthy donors of a similar socioeconomic status and from the same region in Poland. Chromosomal aberrations (CA), sister chromatid exchanges (SCE), high frequency cells (HFC), and proliferative rate index (PRI) were examined from the blood and ras p21 oncoproteins from the plasma. These parameters were used as biomarkers of genotoxic anomalies. All the biomarkers were examined for their relationship to confounding factors of age, sex, smoking habit, and immediate family cancer history. Results were analyzed by a t-test, analysis of variance (ANOVA), and stepwise multivariate regression analysis. All types of CA (including and excluding gaps), percent aberrant cells, SCE, and ras p21 oncoproteins were statistically significantly higher in cancer patients than in the healthy donors. Although there were smaller numbers of females in the cancer patients group who were older than the males, there was a difference due to sex (gender) with statistically significant increases in females for CA, SCE, and HFC, but there was no increase for ras p21 oncoproteins. Cytogenetic damage was not related to other cancers in the immediate families of the groups. All major CA parameters differed significantly between smokers and non-smokers in the cancer patients group, and SCE and HFC differed in the healthy donors group. Such parameters also showed a significant variability with the number of cigarettes smoked and the years of smoking habit. Multivariate regression analyses showed a significant association between cytogenetic damage, ras p21 oncoproteins, and cancer. In conclusion, cytogenetic damage and ras p21 oncoproteins in this study appear to be biomarkers associated with cancer, but have not been proved causally, and confounding factors such as age, sex (gender), and smoking can have an impact on them.

Adult↗

PubMed2005

Standardized approach to proteome profiling of human serum based on magnetic bead separation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

BACKGROUND: Magnetic bead purification for the analysis of low-abundance proteins in body fluids facilitates the identification of potential new biomarkers by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The aims of our study were to establish a proteome fractionation technique and to validate a standardized blood sampling, processing, and storage procedure for proteomic pattern analysis. METHODS: We used magnetic bead separation for proteome profiling of human blood by MALDI-TOF MS (mass range, 1000-10,000 Da) and studied the effects on the quality and reproducibility of the proteome analysis of anticoagulants, blood clotting, time and temperature of sample storage, and the number of freeze-thaw cycles of samples. RESULTS: The proteome pattern of human serum was characterized by approximately 350 signals in the mass range of 1000-10,000 Da. The proteome profile showed time-dependent dynamic changes before and after centrifugation of the blood samples. Serum mass patterns differed between native samples and samples frozen once. The best reproducibility of proteomic patterns was with a single thawing of frozen serum samples. CONCLUSION: Application of the standardized preanalytical blood sampling and storage procedure in combination with magnetic bead-based fractionation decreases variability of proteome patterns in human serum assessed by MALDI-TOF MS.

Adult↗

PubMed2006

ZAP-70 expression, as detected by immunohistochemistry on bone marrow biopsies from early-phase CLL patients, is a strong adverse prognostic factor.

Zeta-associated protein-70 (ZAP-70), mostly assessed by flow-cytometry (FC), recently emerged as reliable prognostic factor in chronic lymphocytic leukaemia (CLL) at presentation. We evaluated ZAP-70 expression in 156 CLL patients by immunohistochemistry (IHC) on formalin-fixed bone marrow (BM) biopsies at diagnosis. At presentation, 117 patients (75%) were with Binet stage A, 27 (17%) stage B and 12 (8%) stage C. Median follow-up was 61 months (range 6-242). ZAP-70 was expressed in neoplastic lymphocytes of 69 patients (44%). Concordance between ZAP-70 by IHC and ZAP-70 by FC, immunoglobulin heavy chain variable genes (IGHV) mutational status and CD38 expression was found in 41/46 (89%), 41/49 (80%) and in 60/88 (68%) tested cases, respectively. ZAP-70 expression significantly correlated with advanced Binet stage (B-C), diffuse BM infiltration, increased lactate dehydrogenase (LDH) and beta2-microglobulin serum levels and lymphocyte doubling time <12 months. ZAP-70 positivity was significantly related to poorer time to progression (median 16 months vs 158 of ZAP-70-negative cases) (P<0.0001) and overall survival (median 106 months vs not reached) (P=0.0002); this correlation was confirmed at multivariate analysis. ZAP-70 expression correlated with poorer outcome also when evaluated only in the 117 stage A patients. In conclusion, immunohistological detection of ZAP-70 on formalin-fixed BM biopsies at diagnosis appears a useful methodological approach to identify patients with poor prognosis in CLL.

ADP-ribosyl Cyclase 1↗