Prognostic Marker (prognostic + marker)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Prognostic Marker

  • good prognostic marker
  • important prognostic marker
  • independent prognostic marker
  • novel prognostic marker
  • potential prognostic marker
  • useful prognostic marker

  • Selected Abstracts

    Editorial: Proteinuria in Chronic Kidney Disease in Cats,Prognostic Marker or Therapeutic Target?

    Jonathan Elliott
    No abstract is available for this article. [source]

    p27Kip1 Expression and grading of breast cancer diagnosed on cytological samples

    Giancarlo Troncone M.D.
    Abstract The progressive reduction in p27Kip1 (p27) protein immunohistochemical staining with increasing histological grading is a well-established finding occurring in breast cancer, and its role as diagnostic complement and prognostic marker has been thoroughly evaluated. To clarify whether this test may be applied to breast cytopathology, we performed p27 immunostaining on fresh fine-needle cytology (FNC) samples from 10 benign and 40 malignant breast lesions. On average, p27 immunostaining was significantly lower in carcinomas than in benign lesions (P < 0.005). In particular, among carcinomas, p27 immunostaining progressively reduced from well-to poorly differentiated lesions (G1 vs. G2, P < 0.05; G1 vs. G3, P < 0.001; G2 vs. G3; P < 0.001). A similar trend was noted in a subgroup of 20 matched FNCs and histological samples of breast carcinomas, when p27 immunostaining on FNCs was stratified according to the histological grading (G1 vs. G2, P = 0.18; G1 vs. G3, P < 0.05; G2 vs. G3, P < 0.05). In addition, p27 immunostaining on FNCs showed a good positive correlation with that on histology (Spearman R = 0.58; P < 0.01), with a diagnostic concordance between samples of 85%, by using the standard 50% positive cell cutoff. Taken in concert, our data suggest that p27 immunostaining is a reliable marker of tumor cell differentiation in breast cytopathology as well as in histopathology. Accordingly, staining FNCs for p27 may be an useful complement in addition to cytological grading in the preoperative assessment of breast cancer. Diagn. Cytopathol. 2004;30:375,380. 2004 Wiley-Liss, Inc. [source]

    Tumor budding as a useful prognostic marker in esophageal squamous cell carcinoma

    M. S. Roh
    SUMMARY, We examined the prognostic significance of tumor budding in patients with esophageal squamous cell carcinoma, particularly in comparison to other routine pathological findings. Fifty-six cases who underwent an esophagectomy were reviewed. We defined tumor budding as an isolated single cancer cell or a cluster composed of fewer than five cancer cells and divided these into two grades; low-grade (< 5 budding foci) and high-grade (, 5 budding foci) within a microscopic field of 200. There were 22 (39.3%) and 34 (60.7%) cases with low- and high-grade budding, respectively. There were significant differences in the patients with low- and high-grade budding in relation to tumor size, pT stage, lymphovascular invasion, perineural invasion, circumferential resection margin involvement, and AJCC stage (P < 0.05). The 3-year survival rates of the patients with low- and high-grade budding were 72.3% and 30.7%, respectively (P = 0.04). We propose that tumor budding may be a pathological marker suggesting high malignancy potential and decreased postoperative survival in patients with esophageal squamous cell carcinoma. [source]

    Association between Endothelial Function and Chronotropic Incompetence in Subjects with Chronic Heart Failure Receiving Optimal Medical Therapy

    ECHOCARDIOGRAPHY, Issue 3 2010
    M.D., Timothy J. Vittorio M.S.
    Objective: Impairment of flow-mediated, endothelium-dependent vasodilatation (FMD) of the brachial artery identifies peripheral endothelial dysfunction in subjects with chronic congestive heart failure (CHF) and is associated with increased morbidity and mortality. To further elucidate the interaction of peripheral and central mechanisms in the syndrome of CHF, we examined the association between endothelial function and chronotropic incompetence, an emerging prognostic marker in CHF. Methods: Thirty subjects with stable New York Heart Association (NYHA) functional class II,III CHF were studied. A vascular ultrasound study was performed to measure brachial artery FMD. The percentage of age-adjusted maximal predicted heart rate (MPHR) reached during cardiopulmonary exercise tolerance testing (CPETT) was used to assess the degree of chronotropic competence. All patients received ACE inhibitors and ,-adrenoceptor blockers. Results: Brachial artery FMD averaged 1.3 2.4% and age-adjusted % MPHR 74.1 11.7%. FMD correlated with % MPHR among all patients (r = 0.60, P = 0.01). FMD and resting heart rate (RHR) did not significantly correlate (r = 0.13, P = 0.55). Conclusions: FMD, a measure of peripheral endothelial dysfunction, and % MPHR, a central determinant of cardiac output, are moderately correlated in heart failure patients receiving optimal medical therapy. Whether a cause-effect relationship underlies this association remains to be investigated. (Echocardiography 2010;27:294-299) [source]

    Osteopontin as a novel prognostic marker in stable ischaemic heart disease: a 3-year follow-up study

    Panagiota Georgiadou
    Eur J Clin Invest 2010; 40 (4): 288,293 Abstract Objectives, Osteopontin (OPN) is a glycoprotein, which may play a major role in the regulation of biological phenomena. Increased levels of OPN have been linked to the presence and to the severity of atherosclerosis. This study was undertaken to assess the prognostic significance of plasma OPN levels in patients with stable ischaemic heart disease (IHD). Methods, In 101 patients with stable IHD and angiographically documented significant coronary artery stenosis, plasma OPN levels were measured at baseline (time of coronary arteriography). Patients were prospectively followed for a median time of 3 years (minimum 225, maximum 39 years). The primary study endpoint was the composite of cardiovascular death, non-fatal myocardial infarction, need for revascularization and hospitalization for cardiovascular reasons. Results, Baseline lnOPN levels were directly related to age (r = 027, P < 0001) and inversely to left ventricular ejection fraction (r = ,032, P < 001). Left ventricular ejection fraction was an independent predictor of plasma OPN levels after adjustment for age and gender (, = ,0013, P = 002). Median OPN value was 55 ng mL,1. In the univariate Cox-regression analysis, OPN levels > 55 ng mL,1 (n = 50) were significantly related to adverse cardiac outcome (HR = 240, 95% CI: 111,523, P = 0027). In multivariate model, OPN levels > 55 ng mL,1 remained statistically significant independent predictor of adverse outcome after adjustment for age, gender, left ventricular ejection fraction and the number of diseased coronary arteries (HR = 288, 95% CI: 109,758, P = 0032). Conclusion, OPN may provide significant prognostic information independent of other traditional prognostic markers in patients with stable IHD. [source]

    Plasma matrix metalloproteinase-3 level is an independent prognostic factor in stable coronary artery disease

    T. C. Wu
    Abstract Background, Recent evidence suggests the important role of matrix metalloproteinases (MMPs) in the progression of atherosclerosis and development of clinical events. We assessed the prognostic value of different plasma MMPs in patients with stable coronary artery disease (CAD). Materials and methods, A total of 165 consecutive nondiabetic patients with angiographically significant CAD (n = 150) or normal coronary angiograms despite exercise-induced myocardial ischemia (cardiac syndrome X, n = 15) and 17 normal subjects were evaluated. In each subject, plasma inflammatory markers including high sensitivity C-reactive protein (hsCRP) and MMP-2, 3 and 9 were measured. In CAD patients, major cardiovascular events including cardiac death, nonfatal myocardial infarction, unscheduled coronary revascularization and hospitalization as a result of unstable angina were prospectively followed up for more than 6 months. Results, Plasma levels of MMPs were significantly higher in CAD patients than in those with cardiac syndrome X and in normal subjects (MMP-2: 91476 1320 vs. 83079 3195 vs. 78308 2840 ng mL,1, P = 0002; MMP-3: 12959 421 vs. 11686 809 vs. 9171 955 ng mL,1, P = 0011; MMP-9: 3142 284 vs. 1140 549 vs. 671 289 ng mL,1, P = 0006). In CAD patients, there were 48 major cardiovascular events during a mean follow-up period of 1774 085 months. The numbers of diseased vessels (HR = 219, 95% CI 120,102, P = 0011), plasma hsCRP (HR = 221, 95% CI 118,411, P = 0013) and MMP-3 level (HR = 246, 95% CI = 115,528, P = 0021) were associated with the development of cardiovascular events. However, only the plasma MMP-3 level was an independent predictor of the adverse events in CAD patients (HR = 247, 95% CI 110,554, P = 0028). Conclusions, Plasma MMP levels were increased in CAD patients. Plasma MMP-3 level, rather than hsCRP, was an independent prognostic marker for future cardiovascular events, suggesting its potential role in risk stratification and clinical management of stable CAD. [source]

    Osteopontin and the skin: multiple emerging roles in cutaneous biology and pathology

    Franziska Buback
    Abstract:, Osteopontin (OPN) is a glycoprotein expressed by various tissues and cells. The existence of variant forms of OPN as a secreted (sOPN) and intracellular (iOPN) protein and its modification through post-translational modification and proteolytic cleavage explain its broad range of functions. There is increasing knowledge which receptors OPN isoforms can bind to and which signaling pathways are activated to mediate different OPN functions. sOPN interacts with integrins and CD44, mediates cell adhesion, migration and tumor invasion, and has T helper 1 (Th1) cytokine functions and anti-apoptotic effects. iOPN has been described to regulate macrophage migration and interferon-, secretion in plasmacytoid dendritic cells. Both sOPN and iOPN, through complex functions for different dendritic cell subsets, participate in the regulation of Th cell lineages, among them Th17 cells. For skin disease, OPN from immune cells and tumor cells is of pathophysiological relevance. OPN is secreted in autoimmune diseases such as lupus erythematosus, and influences inflammation of immediate and delayed type allergies and granuloma formation. We describe that OPN is overexpressed in psoriasis and propose a model to study OPN function in psoriatic inflammation. Through cytokine functions, OPN supports immune responses against Mycobacteria and viruses such as herpes simplex virus. OPN is also implicated in skin tumor progression. Overexpression of OPN influences invasion and metastasis of melanoma and squamous cell carcinoma cells, and OPN expression in melanoma is a possible prognostic marker. As OPN protein preparations and anti-OPN antibodies may be available in the near future, in-depth knowledge of OPN functions may open new therapeutic approaches for skin diseases. [source]

    Significance of circulating endothelial progenitor cells in hepatocellular carcinoma,

    HEPATOLOGY, Issue 4 2006
    Joanna W. Y. Ho
    This study evaluated the significance of circulating bone marrow-derived endothelial progenitor cells (EPCs) in patients with hepatocellular carcinoma (HCC), a solid tumor with rich neovasculature. Eighty patients with HCC were recruited for the study, and 16 patients with liver cirrhosis and 14 healthy subjects were also included for comparison. Blood samples were taken before treatment. Total mononuclear cells were isolated from peripheral blood, preplated to eliminate mature circulating endothelial cells, and colony-forming units (CFUs) formed by circulating EPCs were counted. To validate the CFU scores, FACS quantification of EPCs using CD133, VEGFR2, and CD34 as markers was performed in 30 cases. Our study showed significantly higher mean CFU scores in patients with HCC compared to patients with cirrhosis and healthy controls (P = .001 and .009, respectively). Furthermore, the CFU scores of patients with HCC positively correlated with levels of serum ,-fetoprotein (r = .303, P = .017), plasma VEGF (r = .242, P = .035), and plasma interleukin-8 (IL-8) (r = .258, P = .025). Patients with unresectable HCC had higher CFU scores than patients with resectable tumors (P = .027). Furthermore, for those who underwent curative surgery, higher preoperative CFU scores were observed in patients with recurrence within 1 year compared with those who were disease-free after 1 year (P = .013). In conclusion, higher circulating levels of EPCs are seen in patients with advanced unresectable HCC as compared to patients with resectable HCC or those with liver cirrhosis. Our evidence supports the potential use of circulating level of EPCs as a prognostic marker in patients with HCC. (HEPATOLOGY 2006;44:836,843.) [source]

    Cytoplasmic ,-catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomas

    HISTOPATHOLOGY, Issue 1 2010
    Michael G A Norwood
    Norwood M G A, Bailey N, Nanji M, Gillies R S, Nicholson A, Ubhi S, Darnton J J, Steyn R S, Womack C, Hughes A, Hemingway D, Harrison R, Waters R & Jankowski J A (2010) Histopathology,57, 101,111 Cytoplasmic ,-catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomas Aims:, ,-Catenin is an important molecule in cancer biology. Membranous ,-catenin enhances cellular differentiation and inhibits invasion by its action on E-cadherin. The aim was to ascertain whether the cellular expression of these molecules in colorectal and oesophageal cancer specimens is associated with survival in patients with gastrointestinal cancer. Methods and results:, Tumour samples from 149 patients undergoing resection for colorectal adenocarcinoma and 147 patients undergoing resection for oesophageal adenocarcinoma were retrospectively analysed using immunohistochemical techniques to assess ,-catenin expression. Increasing ,-catenin expression in the cytoplasm was associated with improved survival for colorectal cancer cases on both univariate (P = 0.003) and multivariate (P = 0.01) analysis. In addition, increased expression in the most recent cohort of oesophageal adenocarcinoma patients was associated with improved TNM staging (P = 0.007). Membrane expression was weakly associated with survival in colorectal cancer on univariate analysis (P = 0.09), but not on multivariate analysis (P = 0.21). Complete absence of ,-catenin expression at all three sites was associated with reduced 5-year survival in colorectal cancer. Conclusions:, This is one of the largest prognostic studies of ,-catenin in gastrointestinal adenocarcinoma. It shows that low levels of cytoplasmic ,-catenin expression are associated with reduced survival in patients with colorectal cancer as well as worse TNM staging in oesophageal adenocarcinoma (a recognized surrogate end-point for survival). We believe this is the first time that this has been reported. This finding should be tested prospectively in oncological trials to validate whether the presence of cytoplasmic ,-catenin could be used as a prognostic marker for less aggressive disease. [source]

    Expression of multidrug resistance-associated protein 1 in invasive ovarian carcinoma: implication for prognosis

    HISTOPATHOLOGY, Issue 6 2009
    Areeg Faggad
    Aims:, Multidrug resistance is a major impediment in chemotherapeutic treatment of ovarian carcinoma patients. The aim of this study was to investigate the expression of multidrug resistance-associated protein 1 (MRP1) and to assess the possible associations with clinicopathological variables and patient outcome in primary ovarian carcinoma. Methods and results:, Tumour specimens from 129 patients were obtained before chemotherapy and analysed by immunohistochemistry on tissue microarrays, and by real-time reverse transcriptase-polymerase chain reaction on RNA extracted from formalin-fixed paraffin-embedded tissue specimens using a new technique. Significantly increased MRP1 protein expression was observed in high-grade tumours (P = 0.005) and advanced International Federation of Gynaecology and Obstetrics stages (P = 0.036). On univariate Kaplan,Meier analysis, patients with higher expression of MRP1 protein had significantly decreased overall survival (P = 0.006). On multivariate Cox regression analysis, MRP1 protein expression retained its significance as an independent negative prognostic marker for overall survival (hazard ratio = 6.52, P = 0.003). Furthermore, MRP1 expression correlated with topoisomerase II, expression both at mRNA and protein level (P < 0.001 and P = 0.023, respectively). Conclusion:, In summary, in patients with primary ovarian cancer, overexpression of MRP1 is an adverse marker for patient outcome and cancer aggressiveness. Our data provide a translational basis for further clinical studies on the predictive value of MRP1 expression for response to chemotherapy. [source]

    Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrence

    Martin Spahn
    Abstract Emerging evidence shows that microRNAs (miR) are involved in the pathogenesis of a variety of cancers, including prostate carcinoma (PCa). Little information is available regarding miR expression levels in lymph node metastasis of prostate cancer or the potential of miRs as prognostic markers in this disease. Therefore, we analyzed the global expression of miRs in benign, hyperplastic prostate tissue (BPH), primary PCa of a high risk group of PCa patients, and corresponding metastatic tissues by microarray analysis. Consistent with the proposal that some miRs are oncomirs, we found aberrant expression of several miRs, including the downregulation of miR-221, in PCa metastasis. Downregulation of miR-221 was negatively correlated with the expression of the proto-oncogen c-kit in primary carcinoma. In a large study cohort, the prostate-specific oncomir miR-221 was progressively downregulated in aggressive forms of PCa. Downregulation of miR-221 was associated with clinicopathological parameters, including the Gleason score and the clinical recurrence during follow up. Kaplan,Meier estimates and Cox proportional hazard models showed that miR-221 downregulation was linked to tumor progression and recurrence in a high risk prostate cancer cohort. Our results showed that progressive miR-221 downregulation hallmarks metastasis and presents a novel prognostic marker in high risk PCa. This suggests that miR-221 has potential as a diagnostic marker and therapeutic target in PCa. [source]

    Prognostic significance of integrin-linked kinase1 overexpression in astrocytoma

    Jun Li
    Abstract Integrin-linked kinase 1 (ILK1), a member of the serine/threonine kinases, has been demonstrated to be associated with numerous biological and pathological processes. However, the clinical and functional significance of ILK1 expression has not been characterized previously in human astrocytoma. In this study, we found that ILK1 was overexpressed, at both mRNA and protein levels, in astrocytoma cell lines as compared with normal human astrocytes. The ILK1 mRNA and protein were significantly increased up to 5.6-fold and 10.1-fold, respectively, in primary astrocytoma in comparison with the paired adjacent noncancerous brain tissues obtained from the same patient. Furthermore, immunohistochemical analysis revealed that ILK1 protein was positive in 208 of 228 (91.2%) paraffin-embedded archival astrocytoma specimens. Statistical analysis suggested that the upregulation of ILK1 was significantly correlated with the histological grading of astrocytoma (p = 0.000), and that patients with high ILK1 level exhibited shorter survival time (p < 0.001). Multivariate analysis revealed that ILK1 upregulation might be an independent prognostic indicator for the survival of patients with astrocytoma. Taken together, our results suggest that ILK1 might represent a novel and useful prognostic marker for astrocytoma and play a role during the development and progression of the disease. [source]

    Phosphoglycerate kinase 1 a promoting enzyme for peritoneal dissemination in gastric cancer,

    Derek Zieker
    Abstract Peritoneal carcinomatosis is a frequent finding in gastric cancer associated with a poor prognosis. The features that enable gastric tumors to disseminate are poorly understood until now. Previously, we showed elevated mRNA levels of phosphoglycerate kinase 1 (PGK1), an adenosine triphosphate-generating enzyme in the glycolytic pathway, the chemokine receptor 4 (CXCR4), the corresponding chemokine ligand 12 (CXCL12) and ,-catenin in specimens from gastric cancer patients with peritoneal carcinomatosis. In this study, the influence of PGK1 on CXCR4 and ,-catenin was assessed as well as the invasiveness of PGK1 overexpressing cancer cells. In this current study, we found that PGK1 regulates the expression of CXCR4 and ,-catenin at the mRNA and protein levels. On the other hand, CXCR4 regulates the expression of PGK1. Plasmid-mediated overexpression of PGK1 dramatically increased the invasiveness of gastric cancer cells. Interestingly, inhibition of CXCR4 in cells overexpressing PGK1 produced only a moderate reduction of invasiveness suggesting that, PGK1 itself has a critical role in tumor invasiveness. Immunohistochemistry in specimens from diffuse gastric cancer patients also revealed an overexpression of PGK1 in patients with development of peritoneal carcinomatosis. Therefore, PGK1 may be a crucial enzyme in peritoneal dissemination. Together these findings suggest that the enhanced expression of PGK1 and its signaling targets CXCR4 and ,-catenin in gastric cancer cells promote peritoneal carcinomatosis. Thus, PGK1 may serve as prognostic marker and/or be a potential therapeutic target to prevent dissemination of gastric carcinoma cells into the peritoneum. [source]

    EBAG9 is a tumor-promoting and prognostic factor for bladder cancer

    Jinpei Kumagai
    Abstract Upregulation of EBAG9 expression has been observed in several malignant tumors such as advanced breast and prostate cancers, indicating that EBAG9 may contribute to tumor proliferation. In the present study, we assess the role of EBAG9 in bladder cancer. We generated human bladder cancer EJ cells stably expressing FLAG-tagged EBAG9 (EJ-EBAG9) or empty vector (EJ-vector), and investigated whether EBAG9 overexpression modulates cell growth and migration in vitro as well as the in vivo tumor formation of EJ transfectants in xenograft models of BALB/c nude mice. EBAG9 overexpression promoted EJ cell migration, while the effect of EBAG9 to cultured cell growth was rather minimal. Tumorigenic experiments in nude mice showed that the size of EJ-EBAG9-derived tumors was significantly larger than EJ-vector-derived tumors. Loss-of-function study for EBAG9 using small interfering RNA (siRNA) in xenografts with parental EJ cells showed that the intra-tumoral injection of EBAG9 siRNA markedly reduced the EJ tumor formation compared with control siRNA. Furthermore, immunohistochemical study for EBAG9 expression was performed in 60 pathological bladder cancer specimens. Intense and diffuse cytoplasmic immunostaining was observed in 45% of the bladder cancer cases. Positive EBAG9 immunoreactivity was closely correlated with poor prognosis of the patients (p = 0.0001) and it was an independent prognostic predictor for disease-specific survival in multivariate analysis (p = 0.003). Our results indicate that EBAG9 would be a crucial regulator of tumor progression and a potential prognostic marker for bladder cancer. 2008 Wiley-Liss, Inc. [source]

    Reduction of TIP30 correlates with poor prognosis of gastric cancer patients and its restoration drastically inhibits tumor growth and metastasis

    Xiaohua Li
    Abstract Gastric cancer is an aggressive cancer with poor prognosis. Identification of precise prognostic marker and effective therapeutic target is important in the treatment of gastric cancer. TIP30, a newly identified tumor suppressor, appears to be involved in multiple functions including tumorigenic suppression, apoptosis induction and diminishing angiogenic properties. Here, the level of TIP30 expression was determined in gastric cancer, and the impact of its alteration on cancer biology and clinical outcome was investigated. We found that TIP30 protein was absent or reduced in gastric cancer cell lines. There was also a loss or substantial decrease of TIP30 expression in 106 cases of gastric tumors as compared with that in normal gastric mucosa (p < 0.05), which was significantly associated with inferior survival duration. In a Cox proportional hazards model, TIP30 expression independently predicted better survival (p < 0.05). We also restored TIP30 protein expression in human gastric cancer-derived cells AGS and MKN28 lacking endogenous TIP30 protein to study the effects of TIP30 expression on cell proliferation, cell kinetics, tumorigenicity and metastasis in BALB/c nude mice and found that adenoviral-mediated restoration of TIP30 expression led to downregulation of cyclin D1, Bcl-2, Bcl-xl, but to upregulation of p27, Bax, p53, caspase 3 and 9 expression, cell cycle G0/G1 arrest and apoptosis in vitro, and dramatic attenuation of tumor growth and abrogation of metastasis in animal models. Taken together, the present work revealed a novel function of TIP30, which can possibly be used as an independent prognostic factor and a potential therapeutic target for gastric cancer. 2008 Wiley-Liss, Inc. [source]

    REG1A expression is a prognostic marker in colorectal cancer and associated with peritoneal carcinomatosis

    Christian Astrosini
    Abstract By expression profiling of early staged colon carcinomas, we found regenerating islet-derived 1 alpha (REG1A) to be upregulated in patients with an unfavorable clinical outcome. For validation, REG1A expression was quantified in another colorectal cancer (CRC) patient cohort by Taqman PCR. Aside from tumor and normal tissue from 63 nonpretreated CRC patients, 31 mucosa biopsies from healthy individuals as well as 22 adenomas were included in the investigation. REG1A was significantly upregulated in tumor specimens (p < 0.001) and adenoma (p < 0.01) as compared to normal colorectal tissue. REG1A expression in normal peritumoral tissue in turn proved to be significantly elevated compared to mucosa from healthy individuals (p < 0.01). Determination of REG1A expression might be useful for early tumor diagnosis with a sensitivity of 90.6%, and a specificity of 77.9%. REG1A expression was significantly increased in tumors with peritoneal carcinomatosis (p < 0.01). Moreover, REG1A turned out to be a significant predictor of disease-free survival (p < 0.05). In conclusion, we present evidence that REG1A is a molecular marker of prognostic value and is associated with peritoneal carcinomatosis in CRC. REG1A turned out to be already significantly raised in peritumoral normal tissue compared to mucosa from healthy individuals, suggesting a molecular field effect of secreted REG1A. 2008 Wiley-Liss, Inc. [source]

    Survivin in esophageal cancer: An accurate prognostic marker for squamous cell carcinoma but not adenocarcinoma

    Antonio Rosato
    Abstract We quantified the expression of survivin, both as mRNA in real-time PCR and protein in immunohistochemistry, in tumor samples of 112 patients with esophageal cancer (56 squamous cell carcinomas and 56 adenocarcinomas). Overall survival of squamous cell carcinoma patients with high survivin mRNA levels was significantly less than that of patients with low survivin mRNA levels (p = 0.0033). Distribution pattern of survivin (nuclear vs. cytoplasmic or mixed) was not correlated to survival, while the extent of immunostaining was significantly correlated to survivin mRNA values (p = 0.016) and had prognostic relevance in univariate analysis (p = 0.0012). Cox's proportional-hazard regression model showed that tumor survivin expression in esophageal squamous cell carcinoma was the most important prognostic factor, independent of tumor stage and other histopathological factors, both as mRNA relative value (p = 0.0259) and protein immunostaining (p = 0.0147). In esophageal adenocarcinoma, survivin expression and pattern of distribution had no prognostic relevance. Thus, quantifying survivin expression provides a prognostic marker only for esophageal squamous tumors. 2006 Wiley-Liss, Inc. [source]

    Loss of intercellular adhesion activates a transition from low- to high-grade human squamous cell carcinoma

    Alexander Margulis
    Abstract The relationship between loss of intercellular adhesion and the biologic properties of human squamous cell carcinoma is not well understood. We investigated how abrogation of E-cadherin-mediated adhesion influenced the behavior and phenotype of squamous cell carcinoma in 3D human tissues. Cell-cell adhesion was disrupted in early-stage epithelial tumor cells (HaCaT-II-4) through expression of a dominant-negative form of E-cadherin (H-2Kd -Ecad). Three-dimensional human tissue constructs harboring either H-2Kd -Ecad-expressing or control II-4 cells (pBabe, H-2Kd -Ecad,C25) were cultured at an air-liquid interface for 8 days and transplanted to nude mice; tumor phenotype was analyzed 2 days and 2 and 4 weeks later. H-2Kd -Ecad-expressing tumors demonstrated a switch to a high-grade aggressive tumor phenotype characterized by poorly differentiated tumor cells that infiltrated throughout the stroma. This high-grade carcinoma revealed elevated cell proliferation in a random pattern, loss of keratin 1 and diffuse deposition of laminin 5 ,2 chain. When II-4 cell variants were seeded into type I collagen gels as an in vitro assay for cell migration, we found that only E-cadherin-deficient cells detached, migrated as single cells and expressed N-cadherin. Function-blocking studies demonstrated that this migration was matrix metalloproteinase-dependent, as GM-6001 and TIMP-2, but not TIMP-1, could block migration. Gene expression profiles revealed that E-cadherin-deficient II-4 cells demonstrated increased expression of proteases and cell-cell and cell-matrix proteins. These findings showed that loss of E-cadherin-mediated adhesion plays a causal role in the transition from low- to high-grade squamous cell carcinomas and that the absence of E-cadherin is an important prognostic marker in the progression of this disease. 2005 Wiley-Liss, Inc. [source]

    Cyclin E expression in papillary thyroid carcinoma: Relation to staging

    Jan Brzezi
    Abstract Cyclin E plays a pivotal role in the regulation of G1-S transition and relates to malignant transformation of the cells. However, the clinical significance of cyclin E expression in patients with papillary thyroid carcinoma (PTC) remains unknown. We examined by immunohistochemistry the expression of cyclin E in 41 resected PTCs in pathologic stages from pT1a to pT4 and analyzed its relation to clinicohistopathologic factors. The positive staining was divided into 3 grades: no expression if less than 10%, expression if 11,50% and overexpression if more than 50% of the nuclei of tumor cells were stained positively. Cylin E expressions were observed in 75.6% of analyzed PTCs but only 60% of papillary microcarcinomas (PMCs) were immunopositive for cyclin E expression. However, cyclin E staining was observed in 90.4% of PTCs in a group with TNM higher than pT1a. The staining index was significantly different between the PMCs and the rest of the cancers investigated (14.91% 14.4% vs. 34.03% 23.44%, respectively; p < 0.005) and we observed positive relation between the staining index and factor T of staging of PTCs. All the lymph node metastases coexisted with cyclin E expression and most, but not all, of them coexisted with cyclin E overexpression. These findings indicate that cyclin E may play a key role for the oncogenesis and biologic behavior of PTC. If our results are confirmed in a larger study, a high level of cyclin E expression may become a new prognostic marker for PTCs. 2003 Wiley-Liss, Inc. [source]

    Mixed venous oxygen saturation is a prognostic marker after surgery for aortic stenosis

    J. HOLM
    Background: Adequate monitoring of the hemodynamic state is essential after cardiac surgery and is vital for medical decision making, particularly concerning hemodynamic management. Unfortunately, commonly used methods to assess the hemodynamic state are not well documented with regard to outcome. Mixed venous oxygen saturation (SvO2) was therefore investigated after cardiac surgery. Methods: Detailed data regarding mortality were available on all patients undergoing aortic valve replacement for isolated aortic stenosis during a 5-year period in the southeast region of Sweden (n=396). SvO2 was routinely measured on admission to the intensive care unit (ICU) and registered in a database. A receiver operating characteristics (ROC) analysis of SvO2 in relation to post-operative mortality related to cardiac failure and all-cause mortality within 30 days was performed. Results: The area under the curve (AUC) was 0.97 (95% CI 0.96,1.00) for mortality related to cardiac failure (P=0.001) and 0.76 (95% CI 0.53,0.99) for all-cause mortality (P=0.011). The best cutoff for mortality related to cardiac failure was SvO2 53.7%, with a sensitivity of 1.00 and a specificity of 0.94. The negative predictive value was 100%. The best cutoff for all-cause mortality was SvO2 58.1%, with a sensitivity of 0.75 and a specificity of 0.84. The negative predictive value was 99.4%. Post-operative morbidity was also markedly increased in patients with a low SvO2. Conclusion: SvO2, on admission to the ICU after surgery for aortic stenosis, demonstrated excellent sensitivity and specificity for post-operative mortality related to cardiac failure and a fairly good AUC for all-cause mortality, with an excellent negative predictive value. [source]

    PELP1: A novel therapeutic target for hormonal cancers

    IUBMB LIFE, Issue 3 2010
    Dimple Chakravarty
    Abstract Recent studies implicate that the estrogen receptor (ER) coregulator proline-, glutamic acid-, and leucine-rich protein (PELP) 1 as playing critical roles in ER-genomic, ER-nongenomic, and ER-signaling cross talk with growth factor signaling pathways. PELP1 expression is deregulated in hormonal cancers and recent studies further elucidated the molecular mechanisms by which PELP1 regulates hormone therapy response. Although PELP1 is important for normal functions of the ER, the possibility to target ER-PELP1 axis appears to be an effective strategy for preventing hormonal carcinogenesis and therapy resistance. Thus, PELP1 may be useful as prognostic marker for hormonal cancers and PELP1 signaling may be useful to generate targeted therapeutics to overcome hormonal therapy resistance. 2009 IUBMB IUBMB Life, 62(3): 163,169, 2010 [source]

    Serum cystatin C may predict the early prognostic stages of patients with type 2 diabetic nephropathy

    Ayumi Shimizu
    Abstract We determined the relationship between levels of serum cystatin C or serum creatinine (s-Cr) and prognostic stages of type 2 diabetic nephropathy. Serum samples from 174 patients with type 2 diabetes were obtained from Juntendo University Hospital, Tokyo and Juntendo Urayasu Hospital, Chiba, Japan. They were classified into four groups according to the Report of the Ministry of Health and Welfare of Japan as follows: Stage I (normoalbuminuric stage), Stage II (microalbuminuric stage), Stage IIIA (macroalbuminuric stage without renal dysfunction), Stage IIIB (macroalbuminuric stage with renal dysfunction), and Stage IV (renal failure stage). Among these patients, 68 were Stage I, 29 Stage II, 32 Stage IIIA, 17 Stage IIIB, and 28 Stage IV. The levels of serum cystatin C were measured using the Dade Behring Cystatin C assay with automated Dade Behring Nephelometer II (BNII) (Dade Behring Marburg GmbH, Germany). The mean levels of serum cystatin C in Stage IIIA were significantly higher than those in Stage I or II (P<0.00001, P<0.0005, respectively). The mean levels of serum cystatin C in Stage IIIB and Stage IV were also significantly higher than those in Stage I (P<0.00001). However, the mean levels of serum creatinine (s-Cr) in Stage IIIA were not significantly higher than those in Stage I or II. The levels of s-Cr in Stage IIIB and Stage IV were significantly higher than those in Stage I (P<0.00001). Receiver operating characteristic (ROC) plots demonstrated that the area under the curve (AUC) of cystatin C (0.76) was greater than that of s-Cr (0.66). As an early prognostic marker of type 2 diabetic nephropathy, serum cystatin C was better than s-Cr in terms of sensitivity and specificity. It appears that the levels of serum cystatin C may predict early prognostic stages of patients with type 2 diabetic nephropathy. J. Clin. Lab. Anal. 17:164,167, 2003. 2003 Wiley-Liss, Inc. [source]

    Expression of vascular endothelial growth factor in renal cell carcinoma is correlated with cancer advancement

    Ching-Chiang Yang
    Abstract Vascular endothelial growth factor (VEGF) functions as a regulator of neovascularization in malignant cells. VEGF as a mitogen is thought to alter renal cell carcinoma formation and tumor progression. We investigated the expression of the VEGF gene in order to evaluate its clinical significance in renal cell carcinoma. Tissue samples from 198 patients with renal cell carcinoma were examined with an immunohistochemical stain for the expression of the VEGF gene. The expression rate was compared to 34 normal renal cortical samples obtained from renal surgery from noncancer patients. There were significant differences between normal renal cortex (0%) and cancer tissue (54.5%) in positive staining of VEGF protein (P<0.001). With the progression of tumor grade, the positive rate of VEGF gene expression significantly increased. The expression rate of the VEGF gene in the advanced group, such as with lymph node involvement or vein invasion, was greater than that in the locally confined group (P<0.001). The results revealed that expression of the VEGF gene is proportional to the formation and progression of renal cell carcinoma, which may allow VEGF to be used as a prognostic marker for renal cell carcinoma. J. Clin. Lab. Anal. 17:85,89, 2003. 2003 Wiley-Liss, Inc. [source]

    Validation of model for end-stage liver disease score to serum sodium ratio index as a prognostic predictor in patients with cirrhosis

    Xiao-Hui Lv
    Abstract Aim:, To evaluate the prognostic ability of model for end-stage liver disease (MELD) to serum sodium (SNa) ratio (MESO) index and to compare the predictive accuracy of the MESO index with the MELD score and the modified Child,Turcotte,Pugh (CTP) score for short-term survival in cirrhotic patients. Methods:, A total of 256 patients with cirrhosis were retrospectively evaluated. The predictive accuracy of the MESO index, MELD score and modified CTP score were compared by the area under the receiver,operator characteristic curve (AUC). Results:, Using 1-month and 3-month mortality as the end-point, overall, MESO and MELD were significantly better than the CTP score in predicting the risk of mortality at 1 month (AUC, 0.866,0.819 vs 0.722, P < 0.01) and 3 months (AUC, 0.875,0.820 vs 0.721, P < 0.01). In the low MELD group, the AUC of MESO index (0.758, 0.759) and CTP score (0.754, 0.732) were higher than that of the MELD score (0.608, 0.611) at 1 month and 3 months, respectively (P < 0.01). However, in the high MELD group, the AUC of MESO index (0.762, 0.779) and MELD (0.737, 0.773) were higher than that of the CTP score (0.710, 0.752) at 1 month and 3 months, respectively, although there were no significant differences (P > 0.05). With appropriate cut-offs for the MESO index, the mortality rate of patients in high MESO was higher (57.1% at 1 month and 69.2% at 3 months) than that of the low MESO (5.5% at 1 month and 7.9% at 3 months) (P < 0.01). Conclusions:, The MESO index, which adds SNa to MELD, is a useful prognostic marker and is found to be superior to the MELD score and modified CTP score for short-term prognostication of patients with cirrhosis. [source]

    Enhanced expression of mucin 6 glycoprotein in cholangiocarcinoma tissue from patients in Thailand as a prognostic marker for survival

    Peti Thuwajit
    Abstract Background and Aim:, Cholangiocarcinoma (CCA) is a mucin-producing cancer that has poor prognosis. Mucin 6 (MUC6) is a mucin that is normally co-expressed with the trefoil factor family-2 (TFF2) trefoil peptide. Both MUC6 and TFF2 have been reported to be involved in the progression of many types of cancers. The aim of this study was to determine the expression of MUC6 and TFF2 in CCA tissues and associate these results with clinical data. Methods:, MUC6 and TFF2 were detected in CCA tissues by immunohistochemistry. The correlations of MUC6 and TFF2 expressions with clinical data were analyzed. Results:, We determined the significant co-expression of both proteins in serial CCA tissues. The high expressions of MUC6 and TFF2 were demonstrated in 37% and 31% of patients, respectively. The expression levels decreased in the advanced stage of CCA when clinical metastasis was exhibited. The high expression of either protein showed a correlation with prolonged postoperative survival time, but only a high expression of MUC6 is significantly correlated with a 5-year survival rate. A multivariate Cox regression analysis revealed that a low expression of MUC6, high expression of TFF2, age of patients >56 years, tumor size >5 cm, and poorly-differentiated histological type were independent, poor prognostic indicators for CCA. Conclusion:, MUC6 showed a good correlation with the survival of CCA patients. It may be of value to propose that MUC6 is a good prognostic marker for CCA management. [source]

    Monitoring of herpes simplex virus DNA types 1 and 2 viral load in cerebrospinal fluid by real-time PCR in patients with herpes simplex encephalitis

    Lottie Schloss
    Abstract A quantitative polymerase chain reaction (PCR) assay was evaluated retrospectively on 92 cerebrospinal fluid (CSF) samples from 29 patients with herpes simplex virus (HSV) encephalitis with the aim to study if the concentration of HSV genomes can be used as a prognostic marker and for monitoring of antiviral therapy. The results were compared to those obtained previously by nested PCR, and the numbers of HSV genomes/ml were evaluated in correlation to patient outcome and treatment. The aims were to compare the sensitivity of a conventional nested PCR to a quantitative PCR, to investigate the range of HSV genome concentration in initial samples and to evaluate possible relationships between the HSV DNA concentrations in CSF, neopterin levels, and outcome of disease. The 29 initial samples contained between 2,,102 and 42,,106 HSV genomes/ml. There was no apparent correlation between the amount of HSV DNA in the initial samples and income status, initial neopterin levels, or prognosis. The number of HSV genomes/ml declined after treatment in all patients, but HSV DNA was still detectable after day 20 in 3 out of 16 patients. A long duration of genome detectability was found to correlate with poor outcome. There was no difference in sensitivity between the nested PCR and the quantitative PCR. While the quantitative PCR is more rational than a nested PCR, the quantitation of HSV genomes does not seem very useful as a prognostic marker in HSV encephalitis. J. Med. Virol. 81:1432,1437, 2009. 2009 Wiley-Liss, Inc. [source]

    Evaluation of survivin as a prognostic marker in oral squamous cell carcinoma

    Yong-Hun Kim
    J Oral Pathol Med (2010) 39: 368,375 Background:, Poor prognosis of oral squamous cell carcinoma (OSCC) is partly attributed to the lack of significant tumor marker for accurate staging and prognostication. We have evaluated survivin, which is a member of the inhibitor of apoptosis family as a cancer marker associated with proliferation, angiogenesis, oral carcinogenesis, and OSCC patient survival, as we reported a prognostic significance of survivin expression in lymph node previously. Methods:, To evaluate survivin expression in six OSCC cell lines, Western blotting was performed. Hamster oral carcinogenesis model was used to observe changes of survivin expression in oral carcinogenesis. Finally, we assessed the diagnostic and prognostic significance of survivin in a series of 38 primary OSCC through immunohistochemistry (CD31, PCNA) and Kaplan,Meier's test. Results:, Survivin expression was detected in all OSCC cell lines at a varying level but not observed in normal gingival keratinocyte cells. In hamster model, survivin expression was observed from 8 weeks through 16 weeks and the intensity of expression became strong until 16 weeks. Clinicopathological analysis revealed a significant correlation between survivin expression and lymph node metastasis (P = 0.006) and proliferation (P < 0.001). However, there was no significant relationship with differentiation, micro vessel density, and cancer stage based on TNM. Survivin overexpression had a significant negative effect on survival of patients. Conclusions:, These results demonstrate the significant relationship between survivin expression and oral carcinogenesis and aggressiveness of OSCC including survival rate of patient. Survivin therefore may be used as a significant cancer marker to gain prognostic information of OSCC. [source]

    Immunohistochemical evidence of PTEN in oral squamous cell carcinoma and its correlation with the histological malignancy grading system

    Cristiane Helena Squarize
    Abstract PTEN is a tumor suppressor gene that encodes a dual phosphatase protein capable of modulating membrane receptors and interaction of the cell and extracellular stimuli. PTEN regulates cell physiology such as division, differentiation/apoptosis and also migration and adhesion. The expression of PTEN was evaluated by immunohistochemistry in OSCC and compared to a well-established histological malignancy grading system. The well-differentiated OSCC were 59.1% and poorly differentiated were 40.9%. According to PTEN expression, the cases were 45.5% positive (the entire tumor showed stained), 22.7% mixed (both negative and positive cells were present) and 31.8% negative (no staining was seen in the tumor cells). PTEN expression in OSCC was related to the malignancy grade (P < 0.0005). Aggressive tumors with a high score of malignancy did not express PTEN, and clearly, the PTEN expression was present in the epithelium adjacent to the tumor. Negative cells were in the invasion border of the tumor. This result suggests that PTEN is related to histologic pattern and biological behavior of OSCC and may be a used as a prognostic marker in the future. The role of PTEN during carcinogenesis and as a biomarker should be further investigated. [source]

    Osteopontin expression correlates with prognostic variables and survival in clear cell renal cell carcinoma

    Koviljka Matusan MD
    Abstract Background and Objectives Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including tumorigenesis and tumor cell metastasis. Recently, it has been detected in a growing number of human tumors, and assessed as a potential prognostic marker. The aim of this study was to analyze the expression of OPN in normal renal tissue and clear cell renal cell carcinomas (CRCCs), and to assess its prognostic significance. Methods The expression of OPN protein was immunohistochemically analyzed in 171 CRCCs and compared to usual clinicopathological parameters such as tumor size, nuclear grade, pathological stage, Ki-67 proliferation index, and cancer-specific survival. Results In normal renal parenchyma, the expression of OPN was seen in distal tubular epithelial cells, calcifications, and some stromal cells. The upregulation of OPN was observed in 61 CRCCs (35.7%) in the form of cytoplasmic granular staining of various intensities. Statistical analysis showed correlation of the OPN expression with tumor size (P,<,0.001), Fuhrman nuclear grade (P,<,0.001), pathological stage (P,=,0.011), and Ki-67 proliferation index (P,<,0.001). Moreover, patients with OPN-positive tumors had significantly worse prognosis in comparison to patients with tumors lacking OPN protein (P,=,0.004). Conclusion Our results suggest that overexpression of OPN is involved in the progression of CRCC. J. Surg. Oncol. 2006;94:325,331. 2006 Wiley-Liss, Inc. [source]

    Observations on the presence of E domain variants of estrogen receptor-, in the breast tumors

    Vijay L. Kumar PhD
    Abstract Background and Objectives Estrogen receptor-, (ER-,) that exists as multiple splice variants, has been widely used as a prognostic marker in the management of breast cancer. Here we have analyzed the hormone binding E domain splice variants of ER-, in the breast tumors with reference to the immunoreactive receptor. Methods Thirty breast cancer patients undergoing surgery at the All India Institute of Medical Sciences, New Delhi, were analyzed for the splice variants of E domain by RT-PCR. The ER level was determined by ELISA and the samples were considered positive if the receptor levels were ,,15 fmol/mg protein. Results Our results show that exon 4 and 5 deletions were prevalent in both ER-positive and ER-negative categories. While most ER-positive cases expressed wild-type (wt) exon 6,+,7, nearly 40% of ER-negative cases showed deletion of exon 6,+,7. Therefore, deletion of exon 6,+,7 or masking of epitopes could lead to underestimation of ER by ELISA. All the metastasis and recurrence cases had undetectable levels of ER. A significant number of node-positive cases expressed immunoreactive ER and wt exon 6,+,7 (r,=,0.509, P,<,0.37). Conclusions Estimation of ER levels combined with composite analysis of ER variants may be a better prognostic marker for breast cancer. J. Surg. Oncol. 2006;94:332,337. 2006 Wiley-Liss, Inc [source]