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Prognostic Effect (prognostic + effect)
Selected AbstractsConventional cytogenetics in myelofibrosis: literature review and discussionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2009Kebede Hussein Abstract The clinical phenotype of myelofibrosis (MF) is recognized either de novo (primary) or in the setting of polycythemia vera (post-PV) or essential thrombocythemia (post-ET). Approximately one-third of patients with primary MF (PMF) present with cytogenetic abnormalities; the most frequent are del(20q), del(13q), trisomy 8 and 9, and abnormalities of chromosome 1 including duplication 1q. Other less frequent lesions include ,7/del(7q), del(5q), del(12p), +21 and der(6)t(1;6)(q21;p21.3). In general, cytogenetic abnormalities are qualitatively similar among PMF, post-ET MF and post-PV MF although their individual frequencies may differ. Based on prognostic effect, cytogenetic findings in MF are classified as either ,favorable' or ,unfavorable'. The former include normal karyotype or isolated del(20q) or del(13q) and the latter all other abnormalities. Unfavorable cytogenetic profile in both PMF and post-PV/ET MF confers an independent adverse effect on survival; it is also associated with higher JAK2V617F mutational frequency. In addition to their prognostic value, cytogenetic studies in MF ensure diagnostic exclusion of other myeloid neoplasms that are sometimes associated with bone marrow fibrosis (e.g. BCR-ABL1 -positive or PDGFRB -rearranged) and also assist in specific treatment selection (e.g. lenalidomide therapy is active in MF associated with del(5q). [source] Combined analysis of specific KRAS mutation, BRAF and microsatellite instability identifies prognostic subgroups of sporadic and hereditary colorectal cancerINTERNATIONAL JOURNAL OF CANCER, Issue 11 2010Inti Zlobec Abstract Confounding effects of specific KRAS gene alterations on colorectal cancer (CRC) prognosis stratified by microsatellite instability (MSI) and BRAFV600E have not yet been investigated. The aim of our study was to evaluate the combined effects of MSI, BRAFV600E and specific KRAS mutation (Gly , Asp; G12D, Gly , Asp, G13D; Gly , Val; G12V) on prognosis in 404 sporadic and 94 hereditary CRC patients. MSI status was determined according to the Bethesda guidelines. Mutational status of KRAS and BRAFV600E was assessed by direct DNA sequencing. In sporadic CRC, KRAS G12D mutations had a negative prognostic effect compared to G13D and wild-type cancers (p = 0.038). With MSI, specific KRAS and BRAFV600E mutations, 3 distinct prognostic subgroups were observed in univariate (p = 0.006) and multivariable (p = 0.051) analysis: patients with (i) KRAS mutation G12D, G12V or BRAFV600E mutation, (ii) KRAS/BRAFV600E wild-type or KRAS G13D mutations in MSS/MSI-L and (iii) MSI-H and KRAS G13D mutations. Moreover, none of the sporadic MSI-H or hereditary patients with KRAS G13 mutations had a fatal outcome. Specific KRAS mutation is an informative prognostic factor in both sporadic and hereditary CRC and applied in an algorithm with BRAFV600E and MSI may identify sporadic CRC patients with poor clinical outcome. [source] Clinical value of p53, c-erbB-2, CEA and CA125 regarding relapse, metastasis and death in resectable non-small cell lung cancerINTERNATIONAL JOURNAL OF CANCER, Issue 5 2003Marina Pollán Abstract The prognostic value of p53 and c-erbB-2 immunostaining and preoperative serum levels of CEA and CA125 was investigated in a prospective multicentric study including 465 consecutive non-small cell lung cancer (NSCLC) patients with resectable tumors. Four end-points were used: lung cancer death, first relapse (either locoregional or metastasis), loco-regional recurrence and metastasis development. Standard statistical survival methods (Kaplan-Meier and Cox regression) were used. The specificity of the prognostic effect across different types of tumors was also explored, as had been planned in advance. Our results showed, once again, that pathological T and N classifications continue to be the strongest predictors regarding either relapse or mortality. Three of the studied markers seemed to add further useful information, however, but in a more specific context. For example, increased CEA concentration defined a higher risk population among adenocarcinomas but not among people with squamous tumors; and p53 overexpression implied a worse prognosis mainly in patients with well differentiated tumors. The analysis of type of relapse proved to be very informative. Thus, CA125 level was associated with a worse prognosis mainly related with metastasis development. Another interesting result was the influence of smoking, which showed a clear dose-response relationship with the probability of metastasis. For future studies, we recommend the inclusion of different endpoints, namely considering the relationship of markers with the type of relapse involved in lung-cancer recurrence. They can add useful information regarding the complex nature of prognosis. © 2003 Wiley-Liss, Inc. [source] The Relationship Between Self-Rated Health and Mortality in Older Black and White AmericansJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2007Sei J. Lee MD OBJECTIVES: To determine whether the association between self-rated health (SRH) and 4-year mortality differs between black and white Americans and whether education affects this relationship. DESIGN: Prospective cohort. SETTING: Communities in the United States. PARTICIPANTS: Sixteen thousand four hundred thirty-two subjects (14,004 white, 2,428 black) enrolled in the 1998 wave of the Health and Retirement Study (HRS), a population-based study of community-dwelling U.S. adults aged 50 and older. MEASUREMENTS: Subjects were asked to self-identify their race and their overall health by answering the question, "Would you say your health is excellent, very good, good, fair, or poor?" Death was determined according to the National Death Index. RESULTS: SRH is a much stronger predictor of mortality in whites than blacks (c -statistic 0.71 vs 0.62). In whites, poor SRH resulted in a markedly higher risk of mortality than excellent SRH (odds ratio (OR)=10.4, 95% confidence interval (CI)=8.0,13.6). In blacks, poor RSH resulted in a much smaller increased risk of mortality (OR=2.9, 95% CI=1.5,5.5). SRH was a stronger predictor of death in white and black subjects with higher levels of education, but differences in education could not account for the observed race differences in the prognostic effect of SRH. CONCLUSION: This population-based study found that the relationship between SRH and mortality is stronger in white Americans and in subjects with higher levels of education. Because the association between SRH and mortality appears weakest in traditionally disadvantaged groups, SRH may not be the best measure to identify vulnerable older subjects. [source] Gene expression profiling of advanced-stage serous ovarian cancers distinguishes novel subclasses and implicates ZEB2 in tumor progression and prognosisCANCER SCIENCE, Issue 8 2009Kosuke Yoshihara To elucidate the mechanisms of rapid progression of serous ovarian cancer, gene expression profiles from 43 ovarian cancer tissues comprising eight early stage and 35 advanced stage tissues were carried out using oligonucleotide microarrays of 18 716 genes. By non-negative matrix factorization analysis using 178 genes, which were extracted as stage-specific genes, 35 advanced stage cases were classified into two subclasses with superior (n = 17) and poor (n = 18) outcome evaluated by progression-free survival (log rank test, P = 0.03). Of the 178 stage-specific genes, 112 genes were identified as showing different expression between the two subclasses. Of the 48 genes selected for biological function by gene ontology analysis or Ingenuity Pathway Analysis, five genes (ZEB2, CDH1, LTBP2, COL16A1, and ACTA2) were extracted as candidates for prognostic factors associated with progression-free survival. The relationship between high ZEB2 or low CDH1 expression and shorter progression-free survival was validated by real-time RT-PCR experiments of 37 independent advanced stage cancer samples. ZEB2 expression was negatively correlated with CDH1 expression in advanced stage samples, whereas ZEB2 knockdown in ovarian adenocarcinoma SKOV3 cells resulted in an increase in CDH1 expression. Multivariate analysis showed that high ZEB2 expression was independently associated with poor prognosis. Furthermore, the prognostic effect of E-cadherin encoded by CDH1 was verified using immunohistochemical analysis of an independent advanced stage cancer samples set (n = 74). These findings suggest that the expression of epithelial,mesenchymal transition-related genes such as ZEB2 and CDH1 may play important roles in the invasion process of advanced stage serous ovarian cancer. (Cancer Sci 2009) [source] | ||||||||||