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Unfavorable Prognostic Factor (unfavorable + prognostic_factor)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

MUM1/IRF4 Expression Is an Unfavorable Prognostic Factor in B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

CANCER SCIENCE, Issue 6 2002
Masato Ito
B-Cell chronic lymphocytic leukemia (B-CLL)/small lymphocytic lymphoma (SLL) consists of heterogeneous diseases that are distinguished by morphological, immunophenotypic and molecular features. MUM1 (multiple myeloma oncogene 1) is a protooncogene that is deregulated as a result of (6;14)(p25;q32) chromosomal translocation in multiple myeloma, and is also expressed in a variety of malignant lymphoma entities. We examined the expression of MUM1 in B-CLL/SLL, and found that 2 of 4 B-CLL-derived cell lines and 14 of 29 patients' specimens expressed MUM1 by immunohistochemical analysis. MUM1 expression was not associated with CD38 expression, somatic hypermutation of immunoglobulin heavy chain gene variable region (IgVH), or any other clinical characteristics of the patients. Interestingly, the patients who were positive for MUM1 showed shorter overall survival tunes than those who were negative for MUM1 (50% survival: 22 months vs. 82 months) (P=0.0008, log-rank test). Multivariate analysis by Cox's proportional-hazards regression model showed that MUM1 expression and unmutated IgVH status were independent unfavorable prognostic factors in patients with B-CLL/SLL. These findings suggest that MUM1 expression is a useful prognostic factor in B-CLL/SLL. The biological role and mechanism of action of MUM1 in B-CLL/SLL need to be clarified for the development of therapies for patients with the poor prognostic subtype. [source]

Comprehensive analysis of cooperative gene mutations between class I and class II in de novo acute myeloid leukemia

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2009
Yuichi Ishikawa
Abstract Acute myeloid leukemia (AML) has been thought to be the consequence of two broad complementation classes of mutations: class I and class II. However, overlap-mutations between them or within the same class and the position of TP53 mutation are not fully analyzed. We comprehensively analyzed the FLT3, cKIT, N-RAS, C/EBPA, AML1, MLL, NPM1, and TP53 mutations in 144 newly diagnosed de novo AML. We found 103 of 165 identified mutations were overlapped with other mutations, and most overlap-mutations consisted of class I and class II mutations. Although overlap-mutations within the same class were found in seven patients, five of them additionally had the other class mutation. These results suggest that most overlap-mutations within the same class might be the consequence of acquiring an additional mutation after the completion both of class I and class II mutations. However, mutated genes overlapped with the same class were limited in N-RAS, TP53, MLL -PTD, and NPM1, suggesting the possibility that these irregular overlap-mutations might cooperatively participate in the development of AML. Notably, TP53 mutation was overlapped with both class I and class II mutations, and associated with morphologic multilineage dysplasia and complex karyotype. The genotype consisting of complex karyotype and TP53 mutation was an unfavorable prognostic factor in entire AML patients, indicating this genotype generates a disease entity in de novo AML. These results collectively suggest that TP53 mutation might be a functionally distinguishable class of mutation. [source]

Pulmonary fibrosis in myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitides

RESPIROLOGY, Issue 2 2004
Sakae HOMMA
Objective: The association of pulmonary fibrosis (PF) with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitides has not been well documented. The aim of this study was to assess the clinicopathological characteristics of PF in patients who tested positive for MPO-ANCA. Methodology: In this study, 31 patients (17 males and 14 females; mean age, 69 years) diagnosed as having PF with positive MPO-ANCA levels ranging from 10 to 840 EU with a mean of 112.5 EU, were evaluated clinicopathologically. Results: Among 31 patients with PF, 22 had underlying systemic diseases such as collagen vascular diseases, while nine had unknown aetiology. Evidence of glomerulonephritis was demonstrated in 14 patients. The clinical features were a history of dry cough and/or fine crackles in all 31 patients. Chest CT scans showed honeycombing in the lung bases in 26 patients. The histopathological features of the diseased lung tissues in all 11 autopsied cases were compatible with the usual interstitial pneumonia (UIP) pattern. Vasculitis was confirmed in bronchial arteries and/or pulmonary arterioles in five patients. The mortality was as high as 13 of the 31 patients. The causes of death were: deterioration of PF in five (two of whom were associated with pulmonary haemorrhage), lung cancer in two, pneumonia in four, and digestive tract bleeding in two. The survival rates in PF with MPO-ANCA-negative collagen vascular diseases, cryptogenic fibrosing alveolitis (CFA), and PF with positive MPO-ANCA, were compared. The 5-year survival rate in PF with positive MPO-ANCA was worse than in PF with MPO-ANCA-negative collagen vascular diseases and was the same for CFA. Conclusion: Although there was no correlation between MPO-ANCA titres and the activity of PF, this study demonstrated that the presence of positive MPO-ANCA was an unfavorable prognostic factor in patients with PF. [source]

Prediction of lymphatic invasion by peritumoral lymphatic vessel density in prostate biopsy cores

THE PROSTATE, Issue 10 2008
Kenji Kuroda
Abstract BACKGROUND Lymphatic invasion in radical prostatectomy specimens has been suggested to be an unfavorable prognostic factor in clinically localized prostate cancer. Lymphangiogenesis detected by antibodies specific for lymphatic endothelial cells has been associated with lymphatic invasion and lymph node metastasis in prostate cancer. This study was designed to examine whether lymphangiogenesis in prostate biopsy could predict lymphatic spread in radical prostatectomy specimens. METHODS Paraffin-embedded positive biopsy cores obtained from 99 patients who underwent radical prostatectomy at our institution were immunostained with D2-40 monoclonal antibody, which specifically recognizes lymphatic endothelium. The association between lymphatic parameters in prostate biopsy and pathological parameters in radical prostatectomy specimens was analyzed. RESULTS Peritumoral and intratumoral lymphatic (ITL) vessels were observed in 90 (90.9%) and 23 cases (23.2%). Average and maximal peritumoral lymphatic vessel density (PTLD) and the presence of ITL in positive biopsy cores were significantly associated with positive biopsy core rates (P,=,0.0015 for average PTLD, P,<,0.0001 for maximal PTLD, and P,=,0.0038 for ITL) and lymphatic vessel invasion (P,<,0.0001 for average PTLD, P,<,0.0001 for maximal PTLD, and P,=,0.0322 for ITL). Among preoperative parameters, the biopsy Gleason score (P,=,0.0092, HR,=,6.108) and average PTLD (P,=,0.0034, HR,=,1.860) were significant predictors of lymphatic invasion in radical prostatectomy specimens in multivariate analysis. CONCLUSIONS PTLD in prostate biopsy specimens assessed by immunohistochemistry using D2-40 antibody could be a useful parameter for predicting lymphatic spread of clinically localized prostate cancer. Prostate 68:1057,1063, 2008. © 2008 Wiley-Liss, Inc. [source]

Up-regulation of CD40 with juxtacrine activity in human nonsmall lung cancer cells correlates with poor prognosis

CANCER, Issue 3 2008
Keidai Ishikawa MD
Abstract BACKGROUND. CD40 and its ligand, CD154, play a regulatory role in several signaling pathways among lymphocytes. Recently, it was reported that CD40 is expressed in several malignant tumors. However, the clinical impact of CD40 expression in nonsmall cell lung cancer has not been studied widely. METHODS. One hundred twenty-nine surgical specimens of nonsmall cell lung cancer were assessed immunohistochemically for CD40 and CD154 expression, and that expression was correlated with patients' clinicopathologic parameters and outcome. Subsequently, in vitro analysis of CD40-CD154 signaling was performed. RESULTS. Immunohistochemical staining of tumor cells confirmed that 67 patients (51.9%) were positive for CD40, and 76 patients (58.9%) were positive for CD154. The survival of patients who had tumors that were negative for CD40 was significantly better than the survival of patients who had tumors that were positive for CD40 (P = .0004). Multivariate analysis using a Cox regression model indicated that CD40 expression in cancer cells is an independent, unfavorable prognostic factor (risk ratio, 1.855; P = .0403). By using an in vitro juxtacrine growth factor assay, the growth of LK2 cells (CD40-positive/CD154-negative) was accelerated by CD154-positive cancer cells, such as PC10 cells (CD40-negative/CD154-positive), by a juxtacrine mechanism. CONCLUSIONS. The current results suggested that CD40 expression in tumors is associated with a poor prognosis and that the juxtacrine interaction of CD40-CD154 among cancer cells facilitates the development of malignant potential in nonsmall cell lung cancer. Cancer 2008. © 2008 American Cancer Society. [source]

Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinoma

CANCER, Issue 1 2003
Hung-Wei Pan M.S.
Abstract BACKGROUND Intrahepatic metastasis via portal vein spread is an important feature and a crucial unfavorable prognostic factor of hepatocellular carcinoma (HCC). To identify the molecular factors for tumor progression, the authors used differential display (DD) to analyze aberrant gene expression in HCC. The goal of the current study was to elucidate the clinicopathologic and prognostic significance of osteopontin (OPN) in HCC progression. METHODS OPN mRNA levels, which were increased preferentially in HCC in a DD assay and verified with Northern blotting, were measured in 240 surgically removed, unifocal, primary HCCs using the reverse transcription,polymerase chain reaction at the exponential phase. OPN mRNA expression was correlated with clinicopathologic features, particularly portal vein invasion, early tumor recurrence, and prognosis. RESULTS Osteopontin mRNA was overexpressed in 133 tumors (55%). The OPN overexpression was associated closely with ,-fetoprotein elevation (P = 0.001), p53 mutation (P = 0.021), larger tumors (P = 0.002), high-grade HCC (P < 0.001), late-stage HCC (P < 0.001), early tumor recurrence and/or metastasis (P = 0.003), and a lower 10-year survival rate (P = 0.00013). Multivariate analysis revealed that tumor stage and early tumor recurrence were crucial prognostic factors. In early-stage HCC, which has no vascular invasion and a lower early tumor recurrence than late-stage HCC, OPN mRNA overexpression predicted a higher early recurrence rate (P = 0.003). CONCLUSIONS OPN mRNA overexpression was correlated closely with high-grade, late-stage, and early tumor recurrence, which lead to poorer prognosis. Osteopontin overexpression might serve as an unfavorable prognostic factor and a useful marker for predicting early recurrence in early-stage HCC. Cancer 2003;98:119,27. © 2003 American Cancer Society. DOI 10.1002/cncr.11487 [source]

Low expression of p27Kip1 is associated with tumor size and poor prognosis in patients with renal cell carcinoma,

CANCER, Issue 4 2002
Toshiro Migita M.D.
Abstract BACKGROUND Proliferative activity in tumors depends on regulation of the cell cycle. p27Kip1 (p27) plays a pivotal role as a negative regulator of the cell cycle. A decrease in p27 expression has been reported in many kinds of tumors, but little is known regarding p27 in patients with renal cell carcinoma (RCC). METHODS Expression of p27 and the related cyclins (cyclin A, cyclin E, and cyclin D1) was examined immunohistochemically in 67 patients with of clear cell RCC. The Ki-67 labeling index (MIB-1 LI) and clinicopathologic parameters related to a poor prognosis also were analyzed. To determine their prognostic significance, univariate and multivariate survival analyses were performed. RESULTS In tumors, there was considerable immunoreactivity for cyclin A, cyclin D1, and MIB-1, and the mean values for each were 1.08%, 16.1%, and 1.5%, respectively. Cyclin E expression was rare. The expression of p27 was correlated strongly with the expression of cyclin A (correlation coefficient, 0.432; P < 0.0004) and cyclin D1 (correlation coefficient, 0.476; P < 0.0004). Also, an inverse correlation was present between p27 expression and tumor size (P = 0.0377). In univariate analysis, the unfavorable prognostic factors were high TNM stage (P < 0.0001), large tumor size (P = 0.0016), high histologic grade (P = 0.0104), and low p27 expression (P < 0.0001). In multivariate analysis, high TNM stage (P = 0.0035) and low p27 expression (P = 0.0235) were independent prognostic factors for disease specific survival in patients with RCC. CONCLUSIONS The results of this study suggest that low p27 expression may be a significant and independent, unfavorable prognostic factor in patients with renal cell carcinoma. Cancer 2002;94:973,9. © 2002 American Cancer Society. DOI 10.1002/cncr.10338 [source]

High ,-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: Significance of hepatitis virus infection, age, p53 and ,-catenin mutations

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2004
Shian-Yang Peng
Abstract ,-Fetoprotein (AFP) is often elevated in hepatocellular carcinoma (HCC). This study was to elucidate the significance and related factors of AFP elevation in HCC in 781 unifocal HCCs receiving curative hepatectomy. We showed that high AFP (> 200 ng/ml), which was associated with AFP mRNA expression in HCC (p = 0.00001), correlated with major clinicopathologic factors. Younger age (, 55 years; p = 0.00001), hepatitis B surface antigen (HBsAg) in serum (p = 0.00001), p53 mutation (p = 0.008), large tumor (p = 0.00001), vascular invasion (p = 0.00001) and early tumor recurrence (p = 0.00001) were significant associates of high AFP, while anti-HCV in serum and ,- catenin mutation in HCC had less frequent high AFP (p = 0.013 and < 0.0001, respectively). We also showed that HCC with high AFP had a lower 10-year survival (p < 0.0001), particularly in large HCC (p < 0.0001). At univariate analysis, high AFP (p < 0.0001), HBsAg positivity (p = 0.05), p53 mutation (p = 0.0004), liver cirrhosis (p = 0.0094), large tumor (p = 0.0003), vascular invasion (p < 0.0001) and early recurrence (p < 0.0001) were significant unfavorable prognostic factors. In Cox proportional hazards regression analysis, high AFP remained a borderline significance (OR = 1.2; CI = 1.0,1.4) after adjustment for the effect of tumor size and tumor stage (p = 0.0821). Furthermore, the detection of AFP mRNA in the liver of AFP mRNA-positive HCC was associated with more frequent early recurrence (p = 0.0026) and might be a useful marker of intrahepatic spread. We therefore conclude that AFP elevation, more than a coincidental epiphenomenon, appears to contribute to vascular invasion and HCC progression and help to identify subsets of HCC patients with increased risk for early recurrence and poor prognosis after hepatectomy. © 2004 Wiley-Liss, Inc. [source]

Serum KL-6 levels in lung cancer patients with or without interstitial lung disease

JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 5 2010
Kunihiko Miyazaki
Abstract Background: It is not known whether lung cancer patients with interstitial lung disease (ILD) might have higher serum levels of KL-6, a high molecular weight glycoprotein classified as a polymorphic epithelial mucin. In addition, prognosis of these patients with elevated serum KL-6 levels might be poorer than that with normal KL-6 levels, but it has not been well clarified. Methods: Serum KL-6 levels in 273 lung cancer patients with or without ILD, and prognostic significance of elevated serum KL-6 levels in these patients were studied using uni- and multivariate analyses. Results: Serum KL-6 levels were elevated (>500,U/ml) in 73.5% of lung cancer patients with ILD and in 33.7% of those without ILD. Serum KL-6 levels in lung cancer patients with ILD were significantly higher than those without ILD. In lung cancer patients with ILD, elevated serum KL-6 has no prognostic significance, but in those without ILD, however, it was one of the unfavorable prognostic factors. Conclusions: Elevated serum KL-6 levels can be observed in lung cancer patients both with and without ILD. Having ILD has strong prognostic impact in patients with lung cancer. In those without ILD, however, elevated KL-6 levels may be related to poor prognosis. J. Clin. Lab. Anal. 24:295,299, 2010. © 2010 Wiley-Liss, Inc. [source]

Prognostic factors and long-term survivorship in patients with recurrent or metastatic carcinoma of the head and neck,

CANCER, Issue 10 2004
An analysis of two Eastern Cooperative Oncology Group randomized trials
Abstract BACKGROUND The current study was conducted to identify prognostic factors and report the characteristics of long-term survivors in patients with recurrent or metastatic carcinoma of the head and neck who were treated with cisplatin-based combination chemotherapy in two randomized, Phase III trials conducted by the Eastern Oncology Cooperative Group (ECOG) (E1393 and E1395). METHODS The authors analyzed prognostic factors for response and survival by combining data from the E1393 trial, which compared cisplatin plus paclitaxel at two dose levels, with data from the E1395 trial, which compared cisplatin plus paclitaxel with cisplatin plus 5-fluorouracil (5-FU), using logistic regression and Cox regression models. RESULTS A total of 399 eligible patients were included. The median follow-up was 4.7 years. The 1-year overall survival (OS) rate for all patients was 32%, the median OS was 7.8 months, and the objective response rate was 32%. On multivariate analysis, the following were found to be independent unfavorable predictors of objective response: weight loss of > 5%, an ECOG performance status of 1 (vs. 0), residual disease at the primary tumor site, a primary tumor site other than the oropharynx, prior radiation therapy (RT) (P = 0.056), and well/moderate tumor cell differentiation (P = 0.067). Independent unfavorable prognostic factors for OS were weight loss, an ECOG performance status of 1 (vs. 0), well/moderate tumor cell differentiation, a primary tumor in the oral cavity or hypopharynx, and prior RT. The following were found to be independent unfavorable prognostic facotrs for time to disease progression: well/moderate tumor cell differentiation, a oral cavity or hypopharyngeal primary tumor, and prior RT. Patients with , 2 adverse prognostic factors were reported to have a median OS of 1 year, whereas patients with 3,5 adverse prognostic factors were found to have a median OS of 0.5 years (P < 0.0001). Forty-nine patients (12%) survived for , 2 years and 6 patients were alive at 5 years. Two-year survivors were more likely to have achieved an objective response to chemotherapy, have poor tumor cell differentiation, be white, have an ECOG performance status of 0, and have received no prior RT. CONCLUSIONS Clinical parameters and tumor cell differentiation appear to be strong pretreatment predictors of outcome in patients with carcinoma of the head and neck and should be considered in the design of future randomized trials. A small percentage of patients with recurrent head and neck carcinoma can achieve long-term survival. Cancer 2004. © 2004 American Cancer Society. [source]