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Important Prognostic Marker (important + prognostic_marker)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

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

INTERNATIONAL JOURNAL OF CANCER, Issue 4 2006
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]

Cytomorphological variations, proliferation and angiogenesis in the prognosis of cutaneous melanoma

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2003
N. Jonjic
Summary Depth of invasion and stage of the disease are well known prognostic indicators in cutaneous melanoma (CM). However, the role of other parameters, such as the variations in cytomorphology of melanocyte tumours, mitotic activity and angiogenesis is still open to question. The aim of this study was to analyse proliferation by mitotic activity index (MAI) and immunostaining of proliferating cell nuclear antigen (PCNA), and the intensity of neovascularization (microvessel density; MVD) in CM clinical stage I in relation to epithelioid, spindle and nevoid cell type, histological type (superficial spreading melanoma and nodular melanoma), Clark's level and Breslow thickness. Finally, the role of all parameters in the prognosis of CM was evaluated. Statistical analysis demonstrated that cytological characteristics of CM correlate only with Clark's level, while histological types correlate with MAI, PCNA and MVD. MAI and PCNA also showed correlation between groups according to Clark's level and Breslow thickness. Finally, tumour cell PCNA was found to correlate with MVD. Survival of patients with CM correlated significantly with MAI. These results suggest that cytological variation, histological type, PCNA and MVD alone are not independent prognostic parameters, whereas MAI is a potentially important prognostic marker in CM. [source]

DNA repair polymorphisms associated with cytogenetic subgroups in B-cell chronic lymphocytic leukemia,

GENES, CHROMOSOMES AND CANCER, Issue 9 2009
Christina Ganster
Genetic polymorphisms in DNA repair genes can affect the risk of developing different forms of cancer. Therefore, we have studied the putative association of seven single nucleotide polymorphisms (SNPs) in five DNA repair genes with the incidence of chronic lymphocytic leukemia (CLL). We included 461 CLL patients and the same number of age- and sex-matched controls. As chromosomal aberrations are important prognostic markers in CLL, we additionally correlated the SNPs with the occurrence of favorable and unfavorable cytogenetic aberrations in CLL patients. Patients with del(13q) as a sole aberration were allocated to the favorable cytogenetic risk group, and patients with del(17p) and/or del(11q) to the unfavorable cytogenetic risk group. All investigated SNPs were equally distributed between patients with the favorable cytogenetic aberration and controls. However, differences were observed in the distribution of rs13181 in ERCC2 between all CLL patients and controls. Moreover, the clearest differences were found for rs13181 in ERCC2 and rs25487 in XRCC1 between CLL patients with unfavorable cytogenetic aberrations and controls. These data suggest that inborn genetic polymorphisms may predict the outcome of CLL. © 2009 Wiley-Liss, Inc. [source]

Model for end-stage liver disease score to serum sodium ratio index as a prognostic predictor and its correlation with portal pressure in patients with liver cirrhosis

LIVER INTERNATIONAL, Issue 4 2007
Teh-Ia Huo
Abstract Background: The models for end-stage liver disease (MELD) and serum sodium (SNa) are important prognostic markers in cirrhosis. A novel index, MELD to SNa ratio (MESO), was developed to amplify the opposing effect of MELD and SNa on outcome prediction. Methods: A total of 213 cirrhotic patients undergoing hepatic venous pressure gradient (HVPG) measurement were retrospectively analyzed. Results: The MESO index correlated with HVPG (r=0.258, P<0.001) and Child,Pugh score (,=0.749, P<0.001). Using mortality as the end point, the area under receiver operating characteristic curve (AUC) was 0.860 for SNa, 0.795 for the MESO index and 0.789 for MELD (P values all >0.3) at 3 months. Among patients with Child,Pugh class A or B, the MESO index had a significantly higher AUC compared with MELD (0.80 vs. 0.766, P<0.001). A MESO index <1.6 identified 97% of patients who survived at 3 months and the predicted survival rate was 96.5%. In survival analysis, MESO index >1.6 independently predicted a higher mortality rate (relative risk: 3.32, P<0001) using the Cox model. Conclusions: The MESO index, which takes into account the predictive power of both MELD and SNa, is a useful prognostic predictor for both short- and long-term survival in cirrhotic patients. [source]