Home About us Contact
|
Home About us Contact | ||
|
|
||
Poor Differentiation (poor + differentiation)
Selected AbstractsProtein phosphatase 1, is required for murine lung growth and morphogenesisDEVELOPMENTAL DYNAMICS, Issue 4 2004Kadija-Kathy Hormi-Carver Abstract Protein phosphatase 1 (PP1) plays important roles in cell cycle control and apoptosis, two processes that impinge on morphogenesis and differentiation. Following the precedent set by other molecules regulating the cell cycle and apoptosis, we hypothesized that PP1 may have context-specific roles in development. Therefore, we have studied the spatial and temporal expression of PP1, during murine lung development and determined the consequences of loss of PP1, function on branching morphogenesis. By using an immunohistochemical approach, we show here that PP1, was expressed throughout the epithelium and mesenchyme upon the emergence of the lung primordium on embryonic day 10, with immunostaining exclusively extranuclear. During the late pseudoglandular stage, PP1, was predominantly expressed in the distal lung epithelium, whereas the mesenchyme contained very little or no PP1, protein. Peri- and postnatally, PP1, immunostaining was mostly nuclear in apparently differentiated cells, as judged by colocalization with well-known markers for lung differentiation. Exposure of fetal lung explants to antisense oligodeoxynucleotides against PP1,, resulted in decreased overall size of the cultured lung, a defect in forming new airways, lack of expression of surfactant protein C, and histologic signs of poor differentiation. These data suggest that PP1, is required for branching morphogenesis and differentiation. Developmental Dynamics 229:791,801, 2004. © 2004 Wiley-Liss, Inc. [source] Prognostic evaluation of epidermal fatty acid-binding protein and calcyphosine, two proteins implicated in endometrial cancer using a proteomic approachINTERNATIONAL JOURNAL OF CANCER, Issue 10 2008Zhengyu Li Abstract With the aim to translate the discovery from proteomic research into clinical applications, we identified epidermal fatty acid-binding protein (E-FABP) and calcyphosine (CAPS) by MALDI-Q-TOF MS and validated their overexpressions by immunoblotting. Their expression statuses were examined by immunohistochemistry in 39 normal endometrium, 29 endometrial intraepithelial neoplasia (EIN) and 84 endometrial cancer (EC) cases. We evaluated the correlations to the clinicopathologic characteristics and determined whether these proteins had prognostic significance. Expressions of E-FABP and CAPS were increased 2.64- and 2.18-fold in EC by immunoblotting. Immunoreactivity of both E-FABP and CAPS were stronger in EC than in EIN or normal tissues (p < 0.001 and < 0.001). Stronger immunoreactivity of E-FABP and CAPS were shown to present with poor differentiation (p = 0.032 and 0.001), but no relevance was observed with staging (p = 1.368 and 4.306). Survival analysis indicated that immunoreactivity of CAPS was correlated to poor survival (p = 0.018), but E-FABP status appeared to be no correlation to the clinical outcome of patients (p = 0.865). Multivariate analysis indicated that CAPS might be an independent prognostic factor for survival in patients with EC (p = 0.008). Results demonstrated the ubiquitous overexpressions of E-FABP and CAPS in EC and the correlations to the clinicopathologic parameters. CAPS might be a potential prognostic factor for survival in patients with EC. The research pattern from proteomics to clinical specimens would have widespread applications. © 2008 Wiley-Liss, Inc. [source] Microparticle-associated tissue factor activity: a link between cancer and thrombosis?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2007M. E. T. TESSELAAR Summary. Background:,Cancer, in particular mucinous adenocarcinoma, is associated with venous thromboembolism (VTE). Tissue factor (TF), initiator of coagulation, plays a central role in the paradigm that clotting and tumor growth form a vicious circle, in which hypercoagulability facilitates the aggressive biology of cancer and vice versa. Expression of TF in tumors is associated with poor differentiation and poor prognosis. Patient/methods:,We investigated the association between clinically manifest VTE and procoagulant properties of circulating microparticles (MP) isolated from blood of unselected pancreatic and breast adenocarcinoma patients' consecutive subjects, who presented with ultrasound or CT-scan confirmed VTE, and healthy subjects. Results:,Patients with disseminated breast and pancreatic cancer had significantly increased levels of MP-associated TF activity compared with healthy controls, subjects with idiopathic acute VTE and non-metastatic cancer patients. Patients with both high MP-associated TF-activity and MP-associated epithelial mucin (MUC1) had a lower survival rate at 3,9 months follow-up than those with low TF-activity and no MUC1 expression: the likelihood of survival was 0.42 (95% CI: 0.19, 0.94) for an individual with these two predictor variables present, after adjustment for other factors (age cohort, type of cancer, VTE) in the Cox proportional hazards model. Conclusions:,Our results suggest an important role for MP-associated TF and MUC1 in the pathogenesis of thrombosis in disseminated mucinous adenocarcinoma patients. Future studies should reveal the mechanism underlying the observed associations. [source] Cell type accuracy of transthoracic fine needle aspiration material in primary lung cancerRESPIROLOGY, Issue 2 2001Adnan Yilmaz Objective: The aim of this study was to evaluate the diagnostic accuracy of transthoracic fine needle aspiration (TFNA) materials in establishing the specific cell type in primary lung cancer, and to study the influence of several factors on this accuracy. Methodology: The present study included 129 patients [(12 females, 117 males; mean age 54.6 years (range 25,75)] who underwent thoracotomy. The initial diagnosis was obtained by means of TFNA biopsy in all patients. Transthoracic fine needle aspiration was performed by 22-gauge Chiba needle with fluoroscopy guide in 93 patients and with computed tomography guide in 36 cases. Results: The overall concordance was 73.6% (Kappa = 0.52). The worst agreement was obtained for the large cell carcinoma (40%; Kappa = 0.48). The likelihood of a correct diagnosis using the TFNA specimens was 6.2-fold higher for well-differentiated tumours than for poorly differentiated tumours (P < 0.005). The stage of tumour and diameter of the lesion had no effect on cell agreement. Cell agreement was higher in central lesions than peripheral lesions, but the difference was not statistically significant (P = 0.097). This difference was more significant between patients with central and peripheral epidermoid carcinoma (P = 0.057). Conclusion: In our opinion, cell typing by TFNA may lead to incorrect results in the presence of poor differentiation, mixed tumours and peripheral epidermoid carcinomas. [source] Significance of Des-Gamma-Carboxy Prothrombin in Selection Criteria for Living Donor Liver Transplantation for Hepatocellular CarcinomaAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009M. Fujiki Des-gamma-carboxy prothrombin (DCP) levels reportedly correlate with histological features of hepatocellular carcinoma (HCC). We examined serum DCP as a predictor of HCC recurrence in 144 patients who underwent living donor liver transplantation. Receiver operating characteristics (ROC) analysis revealed superiority of DCP and AFP over preoperative tumor size or number for predicting recurrence. Multivariate analysis revealed tumor size >5 cm, ,11 nodules, and DCP >400 mAU/mL as significant independent risk factors for recurrence. Incidence of microvascular invasion (62% vs. 27%, p = 0.0003) and poor differentiation (38% vs. 16%, p = 0.0087) were significantly higher for patients with DCP >400 mAU/mL than for patients with DCP ,400 mAU/mL. In ROC analysis for patients with ,10 nodules all ,5 cm to predict recurrence, area under the curve was much higher for DCP than for AFP (0.84 vs. 0.69). Kyoto criteria were thus defined as ,10 nodules all ,5 cm, and DCP ,400 mAU/mL. The 5-year recurrence rate for 28 patients beyond-Milan but within-Kyoto criteria was as excellent as that for 78 patients within-Milan criteria (3% vs. 7%). The preoperative DCP level offers additional information regarding histological features, and thus can greatly improve patient selection criteria when used with tumor bulk information. [source] A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer,,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2009S. P. Bach Background: The outcome of local excision of early rectal cancer using transanal endoscopic microsurgery (TEM) lacks consensus. Screening has substantially increased the early diagnosis of tumours. Patients need local treatments that are oncologically equivalent to radical surgery but safer and functionally superior. Methods: A national database, collated prospectively from 21 regional centres, detailed TEM treatment in 487 subjects with rectal cancer. Data were used to construct a predictive model of local recurrence after TEM using semiparametric survival analyses. The model was internally validated using measures of calibration and discrimination. Results: Postoperative morbidity and mortality were 14·9 and 1·4 per cent respectively. The Cox regression model predicted local recurrence with a concordance index of 0·76 using age, depth of tumour invasion, tumour diameter, presence of lymphovascular invasion, poor differentiation and conversion to radical surgery after histopathological examination of the TEM specimen. Conclusion: Patient selection for TEM is frequently governed by fitness for radical surgery rather than suitable tumour biology. TEM can produce long-term outcomes similar to those published for radical total mesorectal excision surgery if applied to a select group of biologically favourable tumours. Conversion to radical surgery based on adverse TEM histopathology appears safe for p T1 and p T2 lesions. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Model-based prediction of defective DNA mismatch repair using clinicopathological variables in sporadic colon cancer patientsCANCER, Issue 7 2010Frank Sinicrope MD Abstract BACKGROUND: Colon cancers with defective DNA mismatch repair (MMR) have a favorable prognosis and may lack benefit from 5-fluorouracil,based adjuvant chemotherapy. The authors developed models to predict MMR deficiency in sporadic colon cancer patients using routine clinical and pathological data. METHODS: TNM stage II and III colon carcinomas (n = 982) from 6 5-fluorouracil,based adjuvant therapy trials were analyzed for microsatellite instability and/or MMR protein expression. Tumor-infiltrating lymphocytes (TILs) were quantified (n = 326). Logistic regression and a recursive partitioning and amalgamation analysis were used to identify predictive factors for MMR status. RESULTS: Defective MMR was detected in 147 (15%) cancers. Tumor site and histologic grade were the most important predictors of MMR status. Distal tumors had a low likelihood of defective MMR (3%; 13 of 468); proximal tumors had a greater likelihood (26%; 130 of 506). By using tumor site, grade, and sex, the logistic regression model showed excellent discrimination (c statistic = 0.81). Proximal site, female sex, and poor differentiation showed a positive predictive value (PPV) of 51% for defective MMR. In a patient subset (n = 326), a model including proximal site, TILs (>2/high-power field), and female sex showed even better discrimination (c statistic = 0.86), with a PPV of 81%. CONCLUSIONS: Defective MMR is rare in distal, sporadic colon cancers, which should generally not undergo MMR testing. Proximal site, poor differentiation, and female sex detect 51% of tumors with defective MMR; substituting TILs for grade increases the PPV to 81%. These data can increase the efficiency of MMR testing to assist in clinical decisions. Cancer 2010. © 2010 American Cancer Society. [source] Analysis of risk factors for distant metastases in squamous cell carcinoma of the oral cavityCANCER, Issue 7 2007Chun-Ta Liao MD Abstract BACKGROUND. The number of patients with oral cavity squamous cell carcinoma (OSCC) is increasing. Because the characteristics of patients with OSCC who develop distant metastases (DM) remain uncertain, the authors analyzed potential risk factors. METHODS. For this report, the authors retrospectively reviewed data from 889 consecutive patients with OSCC who underwent radical surgery from January 1996 to November 2004. Patients were divided into 2 groups according to whether they had either achieved locoregional control (Group A; n = 678 patients) or developed a locoregional recurrence (Group B; n = 211 patients). Cox proportional-hazards models were used to identify independent predictors of the 5-year DM rate. RESULTS. In the entire study cohort, the 5-year DM rate was 9.6% (6.6% for Group A and 21.4% for Group B). In Group A, the number of positive lymph nodes (,5; P = .009) and the presence of extracapsular spread (ECS) (P < .001) were independent risk factors for DM. In Group B, the presence of ECS (P = .008), poor differentiation (P = .040), pathological stage ,III (P = .036), and the presence of neck recurrence (P = .001) were independent prognosticators. CONCLUSIONS. The current results indicated that different risk factor categories according to locoregional control may be used to facilitate the selection of appropriate management for patients with OSCC after they undergo radical surgery. Cancer 2007. © 2007 American Cancer Society. [source] Magnetic resonance imaging in rectal cancer downstaged using neoadjuvant chemoradiation: accuracy of prediction of tumour stage and circumferential resection margin statusCOLORECTAL DISEASE, Issue 5 2008T. Kulkarni Abstract Objective, The aim was to examine the accuracy of magnetic resonance imaging (MRI) in predicting circumferential resection margin (CRM) involvement, T- and N-stage in patients with locally advanced carcinoma of the rectum, who had undergone long-course downstaging chemoradiation (CRT). Method, Patients with rectal cancer were selected for long-course downstaging CRT if their tumour was considered to threaten (,1 mm) or involve the CRM on MRI. Eighty such patients had a repeat MRI at a median of 6 weeks post-CRT followed by surgical excision soon thereafter. The findings on the post-CRT MRI were compared with histological examination of the surgical specimen. Results, For CRM involvement, post-CRT restaging MRI had an accuracy of 81% (65/80) a sensitivity of 54% (7/13), a specificity of 87% (58/67), a positive predictive value of 44% (7/16) and a negative predictive value of 91% (58/64). Accuracy for T- and N-staging was 43% (34/80) and 78% (62/80), respectively. 38% of T-stages were overstaged and 20% understaged. 4% of N-stages were overstaged and 19% understaged. The 13 patients with histological positive CRM had worse clinical outcomes than the 67 patients with negative CRM in terms of disease-free survival (relative risk of reduced DFS 4.6, P = 0.001) and overall survival (relative risk of death 3.6, P = 0.016). Conclusion, Magnetic resonance imaging has good specificity and negative predictive value for predicting an uninvolved CRM post downstaging CRT in locally advanced rectal cancer although sensitivity and positive predictive value for an involved CRM were unsatisfactory. The shortcomings of MRI stem from poor differentiation of viable tumour from posttreatment changes and inability to identify small nodal and tumour deposits. Clinical correlates in this group of patients have confirmed the importance of achieving a clear CRM at surgery. [source] | ||||||||||||||||||||||