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Results for “Biomarker variability”

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PubMed2006

NT-probrain natriuretic peptide predicts complexity and severity of the coronary lesions in patients with non-ST-elevation acute coronary syndromes.

UNLABELLED: NT-probrain natriuretic peptide (NT-proBNP) has been associated with left ventricular (LV) dysfunction and adverse outcome in patients with non-ST-elevation acute coronary syndromes (NSTEACS). However, the underlying pathophysiological mechanisms responsible for this association have not been well established. We sought to explore the relation between NT-proBNP levels and extension of coronary artery disease (CAD) and the presence of more complex and severe coronary lesions. METHODS: This prospective, multicenter angiographic substudy included 585 patients admitted with NSTEACS. Blinded measurements of NT-proBNP and troponin T were performed at a median time of 3 hours after admission and analyzed centrally. Angiograms were read at a core laboratory by 2 independent readers blinded to patient data. Complex coronary lesion was defined as the presence of at least one of the following: thrombus (+), TIMI flow < 2, or ulcerated plaque. RESULTS: NT-probrain natriuretic peptide levels increased proportionally as LV function decreased. The levels of NT-proBNP were directly related to the extent of the CAD. This association was maintained when we analyzed patients with normal LV function (n = 257). Patients with complex coronary lesions or those with at least one of its individual component had higher levels of NT-proBNP compared with those without complex coronary lesions. After adjusting for clinical and electrocardiographic variables and other biomarkers, positive troponin (OR 2.20, 95% CI 1.50-3.22, P < .0001) and supramedian NT-proBNP levels (OR 1.72, 95% CI 1.19-2.47, P = .003) independently contributed to the prediction of complex coronary lesions. CONCLUSION: In this study of patients with NSTEACS, NT-proBNP levels progressively increase with the severity of CAD and degree of LV dysfunction. Increased levels of NT-proBNP independently predict the presence of more complex coronary lesions.

Acute Disease↗

PubMed2004

Within-person variability of urinary 6beta-hydroxycortisol to urinaryl ratios in Caucasian women.

Cortisol is metabolized to 6beta-hydroxycortisol by human cytochrome p450-3A4 (CYP3A4), an important enzyme involved in the metabolism of a variety of exogenous and endogenous compounds. Both cortisol and 6beta-hydroxycortisol are excreted in urine, and the ratio of these steroids has been proposed as an indicator of CYP3A4 activity. We evaluated within-person variability of this biomarker in 10 healthy Caucasian women, aged 23-58 years. Each study participant was asked to provide a fasting morning urine sample once a week consecutively for 8 weeks. Urinary cortisol and 6beta-hydroxycortisol were determined by immunoassay kits purchased from the DiaSorin (Stillwater, MN) and the Stabiligen (Nancy, France), respectively. The coefficients of variation (CV) of urinary 6beta-hydroxycortisol to cortisol ratios from study participants ranged from 16.7 to 51.4% (mean, 31.1%) over the study period. The level of the ratio measured in any single urine sample was correlated reasonably well with the average of the ratios over the 8-week study period from the same woman, with the mean correlation coefficient of 0.79. These results indicated that urinary 6beta-hydroxycortisol to cortisol ratios measured in a spot urine sample may reflect the level of this biomarker over a relatively longer time period in Caucasian women, and thus, it can be used in epidemiologic studies as a biomarker to evaluate the association between CYP3A4 activity and disease risk.

Adult↗

PubMed1999

Interrelationships among biological markers of aging, health, activity, acculturation, and cognitive performance in late adulthood.

In this study a structural equation model of predictors of age differences in cognitive performance in late adulthood was developed. Biological markers of aging (vision, hearing, vibration sense, forced expiratory volume, and grip strength) were used as indicators of a latent variable called BioAge. A sample of 180 community-dwelling women aged 60 to 90 years was assessed. Results showed that BioAge explained all of the age-related variance in cognitive test performance. Physical health and physical activity had direct effects on BioAge. Measures of acculturation explained non-age-related variance in cognitive test performance. Some variables used as biomarkers also explained individual differences in measures of crystallized intelligence and perceptual speed. It is concluded that the association between biomarkers and cognition in old age is due to more than a common statistical association with age.

Acculturation↗

PubMed2026

Pregnancy diet based on ancestral patterns increases growth in subcortical fetal brain regions.

Evidence on the biological basis for maternal nutrition effects on fetal and newborn neurodevelopment remains limited. This randomized controlled trial in Ecuador tested a maternal dietary pattern-derived from empirical studies of nutrition in human evolution and adapted locally-on offspring growth and brain development. Pregnant women (n = 215) in their first trimester were randomized to: 1) control (n = 104); or 2) Mikhuna ("nourish" in Kichwa) intervention (n = 111). The intervention, from 12 wk gestation to birth, consisted of a weekly food delivery (8 eggs, 500 g fish, and a variety of sustainably sourced fruits and vegetables) and a behavior change communication strategy encouraging diet diversity and limiting highly processed foods. Longitudinal data collection occurred at 12 wk, 21 wk, 35 wk gestation, and 2 wk postpartum, and included ultrasound imaging of fetal bone and brain parameters, maternal dietary intakes, anthropometry, socioeconomic and demographic variables, and other biomarkers. At close of intervention, a significantly higher percentage of women met the minimum dietary diversity threshold in Mikhuna (74.5%) vs. control groups (55.8%) (P = 0.004). Generalized linear regression models showed significant differences in Mikhuna compared to control for: corpus callosum length 0.19 cm (95% CI [0.02, 0.35]), gangliothalamic ovoid height 0.15 cm (95% CI [0.03 to 0.26]), and femur length -0.10 cm (95% CI [-0.19, -0.02]) from 21 wk to 35 wk; and corpus callosum Z 0.56 (95% CI [0.03, 1.09]) and femur length Z -0.21 (95% CI [-0.42, 0.00]) at 35 wk. The Mikhuna intervention increased the growth of subcortical fetal brain structures, which have established roles in motor control, cognition, and signal transmission.

Female↗

PubMed2025

ToxAssay: a hierarchical model-driven tool for advanced toxicogenomics biomarker discovery.

MOTIVATION: Understanding the genetic basis of drug-induced toxicity is crucial for drug development. In-silico analysis of toxicogenomics datasets facilitates early detection of toxicity biomarkers. However, existing tools struggle with the complex interdependencies among hierarchically structured variables, leading to inaccurate biomarker identification. To address this limitation, we developed a Hierarchical Linear Model (HLM) and implemented it in the R package ToxAssay, offering extensive functionality for comprehensive toxicity assessment. RESULTS: ToxAssay outperforms existing methods by improving biomarker detection and computational efficiency. Applied to glutathione depletion-induced toxicity, it prioritized 71 key genes and identified 26 core genes with high discriminative accuracy (AUC = 0.97) and strong cross-correlation (Pearson's r = 0.88) with external datasets. Additionally, our advance outcome pathway (AOP) analysis algorithm uncovered disease outcomes linked to glutathione depletion. These findings provide precise insights into the molecular mechanisms driving drug-induced toxicity. AVAILABILITY AND IMPLEMENTATION: ToxAssay is available as an open-source R package at https://github.com/Fun-Gene/toxassay.

Biomarkers↗

PubMed2006

Parallel changes in metabolite and expression profiles in crooked-tail mutant and folate-reduced wild-type mice.

Anomalies in homocysteine (HCY) and folate metabolism are associated with common birth defects and adult diseases, several of which can be suppressed with dietary folate supplementation. Although supplementation reduces the occurrence and severity of neural tube defects (NTDs), many cases are resistant to these beneficial effects. The basis for variable response and biomarkers that predict responsiveness are unknown. Crooked-tail (Cd) mutant mice are an important model of folate-responsive NTDs. To identify features that are diagnostic for responsiveness versus resistance to dietary folate supplementation, we surveyed metabolite and expression levels in liver samples from folate-supplemented, folate-reduced and control diets in Cd mutant and wild-type adult females. Cd homozygotes had normal total homocysteine (tHcy) levels suggesting that folate suppresses NTDs through a mechanism that does not involve modulating serum tHcy levels. Instead, parallel changes in metabolite and expression profiles in folate-supplemented Cd/Cd homozygotes and folate-reduced+/+and Cd/+mice suggest that Crooked-tail homozygotes have a defect in the utilization of intracellular folate. Then, by combining these expression and metabolite profile results with published results for other models and their controls, two clusters were found, one of which included several folate-responsive NTD models and the other previously untested and presumably folate-resistant models. The predictive value of these profiles was verified by demonstrating that NTDs of Ski-/-mutant mice, whose profile suggested resistance to folate supplementation, were not suppressed with dietary folate supplementation. These results raise the possibility of using metabolite and expression profiles to distinguish folate-responsive and resistance adult females who are at risk for bearing fetuses with an NTD.

Animals↗

PubMed2005

Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43-9006, in patients with advanced, refractory solid tumors.

PURPOSE: BAY 43-9006, a novel multikinase inhibitor, prevents tumor growth by combining two antitumor activities: inhibition of both tumor cell proliferation and tumor angiogenesis. This phase I, open-label, nonrandomized, noncontrolled, single-arm, dose escalation study was done to determine the maximum tolerated dose (MTD), safety profile, pharmacokinetic variables, effect on biomarkers, and tumor response with BAY 43-9006 in 19 patients with advanced, refractory solid tumors. EXPERIMENTAL DESIGN: BAY 43-9006 was given orally in repeated cycles of 1-week on/1-week off. The study comprised five dose levels, ranging from 100 mg twice daily (bid) to 800 mg bid. Treatment of each patient continued until unacceptable toxicity, tumor progression, or death. RESULTS: Rash and hypertension were the dose-limiting toxicities at the 800 mg bid dose requiring study drug discontinuation; therefore, the MTD of BAY 43-9006 in this study was determined to be 600 mg bid. BAY 43-9006 was generally well tolerated, with mild to moderate toxicities. Pharmacokinetic analysis showed early absorption followed by delayed secondary peaks and slow terminal elimination. Stable disease was achieved in five patients: one patient showed reduced tumor activity (positron emission tomography scan) and reduced mitogen-activated protein kinase signaling (lower phospho-ERK); one patient remained on treatment until study end point. CONCLUSIONS: The results confirm the favorable safety profile of BAY 43-9006 and support the development of this compound for the treatment of solid tumors.

Adult↗

PubMed2005

Identification of biomarkers for breast cancer in nipple aspiration and ductal lavage fluid.

PURPOSE: To establish a comprehensive proteomic approach for biomarker discovery and validation in breast fluid. EXPERIMENTAL DESIGN: A total of 95 specimens from three institutions were used including 10 nipple aspiration fluid (5 stage I/II cancerous breasts and 5 age-matched healthy controls), 42 ductal lavage fluid from 14 patients with unilateral stage I/II cancer (25 from 9 cancerous breasts and 17 from 7 contralateral breasts), and 42 ductal lavage fluid from 14 high-risk women (multiple ducts repeated lavage). Differentially expressed protein/peptides were discovered by proteomic analysis of training sample, using ProteinChip arrays and surface-enhanced laser desorption ionization (SELDI) time-of-flight mass spectrometry, and validated on independently collected testing samples. After protein identification, ELISA was done to confirm the SELDI findings. RESULTS: We were able to obtain reproducible protein profiles using minimal amount of protein (1 mug) by applying an optimized chip protocol and SELDI. We were able to select cancer-associated biomarkers despite large individual variability by applying both unsupervised and supervised cluster analysis. Furthermore, we were able to train and test candidate biomarkers on independently collected samples and identified one component of a multimarker panel as human neutrophil peptides 1 to 3. CONCLUSIONS: Breast fluid is a rich source of breast cancer biomarkers. In combination with high-throughput novel proteomic profiling technology and multicenter study design, markers that are highly specific to breast cancer can be discovered and validated. Our observations also suggest that persistent elevation of human neutrophil peptide in high-risk women may imply early onset of cancer not yet detectable by current detection method. Proof of this hypothesis requires follow-up on a larger study population.

Adenocarcinoma↗

PubMed2002

The micronucleus and G2-phase assays for human blood lymphocytes as biomarkers of individual sensitivity to ionizing radiation: limitations imposed by intraindividual variability.

As part of a program to assess the applicability of the micronucleus (MN) and G2-phase assays as biomarkers of cancer susceptibility, we investigated the inter- and intraindividual variations of these end points. For the MN assay, unstimulated blood cultures from 14 healthy donors were exposed in vitro to 3.5 Gy 60Co gamma rays; for the G2-phase assay, PHA-stimulated cell cultures were irradiated with a dose of 0.4 Gy 60Co gamma rays in the G2 phase of the cell cycle. Two of the 14 volunteers were assayed 9 times over a period of 1 year. The repeat experiments revealed that the intraindividual variability was not significantly different from the interindividual variability for both the G2-phase and MN assays. Since the intraindividual variability determines the reproducibility of the assay, our results highlight the limitations of these end points in detecting reproducible differences in radiation sensitivity between individuals within a normal population. For example, one donor of the population was identified as being radiosensitive (based on the 90th percentile criterion) but turned out to be normal when the assay was repeated twice. We conclude that the determination of individual radiosensitivity with these two cytogenetic assays is unreliable when based on one blood sample.

Adult↗

PubMed2004

Biomarkers and surrogate endpoints in renal transplantation: present status and considerations for clinical trial design.

Of major importance in clinical trials is the ability to predict individual patient outcome or endpoints using biomarkers, also known as variables or predictors, in as safe, efficient, and accurate a manner as possible. This review addresses the concepts and possible strategies for use of predictor and surrogate biomarkers in the design of clinical trials in renal transplantation. The statistical concepts apply equally well to other organ grafts.

Biomarkers↗

PubMed2006

A multivariate method for measurement error correction using pairs of concentration biomarkers.

PURPOSE: Measurement error is a pervasive problem in behavioral epidemiology, and available methods of correction all have generally untenable assumptions. We propose a multivariate method with more realistic assumptions. METHODS: The method uses two concentration biomarkers for each nutritional variable of interest and structural equation modeling. This produces corrected estimates of the effects on an outcome variable of changing the true exposure variables by one standard deviation, a standardized regression calibration. However, hypothesis testing in original units is preserved. The main assumptions are that certain error correlations between dietary estimates and biomarkers or between biomarkers be close to zero. RESULTS: Two illustrative models used simulated data with the covariance structure of a real data set. The corrections produced often were very substantial. A sensitivity analysis allowed error correlations to depart from zero over a modest range. Root mean square biases show the advantage of the corrected approach. Relatively large calibration studies are needed for adequate precision. CONCLUSIONS: As long as concentration biomarkers are selected carefully, error-corrected multivariate hypothesis testing and standardized effect estimation is possible. With the deviations from assumptions that were tested, the corrected method usually produces much less biased results than an uncorrected analysis.

Bias↗

PubMed2004

Biomarkers: potential uses and limitations.

Biomarkers provide a dynamic and powerful approach to understanding the spectrum of neurological disease with applications in observational and analytic epidemiology, randomized clinical trials, screening and diagnosis and prognosis. Defined as alterations in the constituents of tissues or body fluids, these markers offer the means for homogeneous classification of a disease and risk factors, and the can extend our base information about the underlying pathogenesis of disease. Biomarkers can also reflect the entire spectrum of disease from the earliest manifestations to the terminal stages. This brief review describes the major uses of biomarkers in clinical investigation. Careful assessment of the validity of biomarkers is required with respect to the stage of disease. Causes of variability in the measurement of biomarkers range from the individual to the laboratory. Issues that affect the analysis of biomarkers are discussed along with recommendations on how to deal with bias and confounding.

Biomarkers↗

PubMed2001

Measurement variability of plasma beta-sitosterol and campesterol, two new biomarkers for cancer prevention.

Phytosterols are plant sterols that are structurally similar to cholesterol and are characterized by anti-carcinogenic and anti-atherogenic properties. Beta-sitosterol and campesterol are the predominant phytosterols in blood. The present study aimed to analyse the reproducibility and overtime reliability of plasma beta-sitosterol and campesterol measurements. In order to study the reproducibility of the measurement (technical variability), three healthy premenopausal women donated a sample of their blood. Each blood sample was subdivided into six aliquots and analysed within the same run by the same laboratory technician. The intraclass correlation coefficients (ICCs) of the assay for plasma beta-sitosterol and campesterol were 0.88 and 0.94 (95% confidence intervals low bounds (95% CI(low)) were 0.66 and 0.82), respectively. To study the reliability of beta-sitosterol and campesterol measurement over time, seven premenopausal women were recruited. Over a 6-month period, each woman provided a fasting blood sample once a month at the same time of day, and the same numerical day of the luteal phase of her menstrual cycle (between the 20th and 24th day of her menstrual cycle). All plasma samples from the same individual were processed together at the same time by the same technician at the end of the 6-month period. The overtime ICCs of plasma beta-sitosterol and campesterol were 0.91 (95% CI(low) 0.49) and 0.58 (95% CI(low) 0.31), respectively. The high reproducibility and good overtime reliability of plasma beta-sitosterol and campesterol measurements indicate that they may be suitable for potential clinical and population-based studies on cancer prevention.

Adult↗

PubMed1999

Biomarker responses in human populations: towards a worldwide map.

The discipline of epidemiology studies the determinants of diseases in human populations, identifies causes, determines outcomes and develops prevention strategies. Traditional epidemiology is most useful for studies of acute, relatively common diseases with short incubation periods but less so for studies of chronic low incidence diseases with long incubation periods. Molecular epidemiology, which employs biological responses or biomarkers as surrogates of exposures or effects, can help with the latter. For this reason, there is a great interest in developing and validating biomarkers. DNA damage underlies an important group of chronic diseases with long incubation periods, i.e., cancer. Biomarkers may measure the exposures that induce the DNA damage, the damage itself, or individual susceptibility to damage. Before they can be used for human population research, however, these measures must be validated. Biomarker validation critically depends on field studies. This is accomplished through transitional epidemiological studies that 'bridge the gap' between laboratory and field. Transitional epidemiological studies are of three varieties: (i) Developmental, (ii) Characterization, and (iii) Applied. Biomarkers are the dependent variables in transitional studies. An international network of laboratories for human population monitoring requires yet another dimension for validation, i.e., the comparability of results among laboratories must be determined. This will be achieved by sample sharing projects, with workshops to compare results. Only then can results in one population be compared with results in another. Interlaboratory standardization of assays for biomarkers validated by transitional studies will have far-reaching benefits. It will allow development of worldwide databases of background values for the various biomarkers-or biomarker maps. This, in turn, will facilitate problem identification and eventually constitute the baselines for area-specific population monitoring. Biomarker databases so developed can be compared with worldwide databases for cancer and heritable diseases, validating the former as statistical surrogates of the latter.

Biomarkers↗

PubMed2004

Pharmacogenomic-guided rational therapeutic drug monitoring: conceptual framework and application platforms for atypical antipsychotics.

Atypical antipsychotic agents such as aripiprazole, clozapine, olanzapine, quetiapine and ziprasidone offer many advantages over conventional neuroleptics. These agents reduce negative symptoms of schizophrenia, are effective in treatment refractory cases, and have a markedly lower incidence of extrapyramidal symptoms and tardive dyskinesia. However, there is considerable patient-to-patient variability in therapeutic dose requirements of atypical antipsychotics and the propensity for side effects. Hence, the initial excitement since the introduction of atypical antipsychotics in late 1980s is now shifting towards a focus on individualization of pharmacotherapy and elucidation of the mechanistic basis of interindividual variability in drug response with use of pharmacokinetic and pharmacodynamic biomarkers. Pharmacogenomics, introduced in late 1990s, is the study of variability in drug response using information from the entire genome of a given individual patient. Both pharmacogenomics and conventional therapeutic drug monitoring (TDM) share the similar goal of improving pharmacotherapy through better explanation of individual variability in drug response. Hence, pharmacogenomic biomarkers offer a unique opportunity to complement and expand the scope of traditional TDM in clinical psychopharmacology. Importantly, pharmacogenomics enables the investigation of factors distal to drug exposure in the plasma compartment (e.g. drug targets at the biophase), thereby providing a more complete portrayal of sources of variability in psychotropic drug response. We discuss (1). the definitions for biomarkers and surrogate endpoints in the context of pharmacogenomics, (2). genetic variations in isozyme-specific atypical antipsychotic metabolism in vivo, (3). selected examples of pharmacogenomic variability in pertinent drug targets and, (4). the anticipated roadmap from implementation of pharmacogenomics to changes in healthcare and therapeutic policy. In addition, a conceptual framework that outlines the theoretical advantages of pharmacogenomics-guided TDM is presented using recent clinical applications as precedence.

Antipsychotic Agents↗

PubMed2000

Influence of personal factors on nasal patency and lavage biomarkers in white-collar workers.

Large biological variability between subjects has been shown for both acoustic rhinometry and nasal lavage biomarker concentrations, but relatively little is known about the influence of personal factors on these techniques. The aim was to evaluate if nasal symptoms, acoustic rhinometric measurements and nasal lavage fluid biomarkers are related to age, gender, smoking, atopy or asthma. A standardized nasal investigation was applied in 411 white-collar workers, belonging to three occupational groups: school personnel (n = 234), office workers (n = 89) and hospital workers (n = 88). Lavage fluid analysis included determination of eosinophil cationic protein (ECP), myeloperoxidase (MPO), lysozyme and albumin. Females had smaller nasal dimensions in the anterior part of the nose (p < 0.001), and lower lavage fluid concentrations of ECP (p = 0.004), MPO (p = 0.002), and albumin (p = 0.01). Rhinometric dimensions or lavage fluid biomarker concentrations were not related to age, smoking, atopy or asthma. Some differences in rhinometric and biomarker measurements were observed between the occupational groups, and adjustment was made for occupation. Rhinometric measures and lavage biomarkers were consistently interrelated, which suggests a combined mucosal swelling and inflammatory reaction. This indicates a potential usefulness of a combined use of acoustic rhinometry and lavage biomarkers to study nasal mucosal reactions.

Albumins↗

PubMed2006

Inflammatory biomarkers in blood of patients with acute brain ischemia.

Although many failed surrogate markers are provided in the literature, inflammation may contribute to the outcome of ischemic stroke. In 50 consecutive patients with acute ischemic stroke, in the absence of symptoms and signs of concomitant infection, we evaluated a panel of biomarkers reported to be variably associated with brain ischemia, and correlate their serum level with the brain lesion volume and clinical outcome. Infarct size was calculated on computed tomography (CT) scans by means of the Cavalieri's method. Neurological impairment was scored by using the Glasgow Coma Scale, Glasgow Outcome Scale and National Institutes of Health (NIH) scales at stroke onset and 3-month follow-up. Some markers showed a direct significant correlation with both initial and final NIH scale and with infarct size, particularly tumor necrosis factor alpha (TNF-alpha) (P=0.002), intercellular adhesion molecule-1 (P<0.01) and matrix metalloproteinase-2/9 (P=0.001). In contrast to previous reports, interleukin-6 (IL-6) serum level showed a significant inverse correlation with both final neurological impairment and infarct size (P<0.001). This novel finding allows us suggesting that IL-6, in the context of a complex pro-inflammatory network occurring during stroke, is associated with neuroprotection rather than neurotoxicity in patients with ischemic brain injury.

Acute Disease↗

PubMed1997

Flow cytometric DNA ploidy and S-phase fraction correlate with histopathologic indicators of tumor behavior in colorectal carcinoma.

BACKGROUND: The clinical behavior of colorectal carcinoma is highly variable without reliable predictive biomarkers. Previous reports have shown that flow cytometric DNA analysis may provide valuable prognostic information in these tumors. PURPOSE AND METHODS: This study evaluates the DNA ploidy and the S-phase fraction (SPF) on frozen samples obtained from 61 patients with colorectal carcinoma by using flow cytometry, and it correlates the data with histopathologic features known to affect disease prognosis. Tumors were classified using the World Health Organization's histologic criteria and were staged according the American Joint Committee on Cancer's classification system. Grade of the neoplasm, vascular invasion, and perineural tumor spread were evaluated in every case. RESULTS: Fifty-nine percent of tumors were aneuploid and showed statistically significant higher S-phase values than diploid tumors (22.5 vs. 11.2 percent; P < 0.00001). Mean SPF of the whole series was 17.9 (range, 4.2-44.2) percent. A statistically significant association was found between SPF values and histologic grade (P < 0.0016), nodal status (P < 0.0007), distant metastasis (P < 0.0001), tumor stage (P < 0.0001), venous invasion (P < 0.0002), and lymphatic permeation (P < 0.01) but not with perineural growth and infiltration of the neoplasm through the bowel wall (T). DNA ploidy correlated positively with tumor stage (P < 0.03), and the association between aneuploidy and advanced stages of the disease was statistically significant. CONCLUSIONS: These findings showed that flow cytometric DNA ploidy and SPF, evaluated in fresh samples, are potentially useful parameters to estimate colorectal carcinoma biopathology. Aneuploidy and high replicative neoplastic activity correlated with histopathologic features that are commonly associated with the prognosis of colorectal carcinoma, being SPF-related to disease dissemination and, therefore, an indicator of clinical relevance.

Adult↗