Level of retinoblastoma protein expression correlates with p16 (MTS-1/INK4A/CDKN2) status in bladder cancer.
Recent studies have shown that patients whose bladder cancer exhibit overexpression of RB protein as measured by immunohistochemical analysis do equally poorly as those with loss of RB function. We hypothesized that loss of p16 protein function could be related to RB overexpression, since p16 can induce transcriptional downregulation of RB and its loss may lead to aberrant RB regulation. Conversely, loss of RB function has been associated with high p16 protein expression in several other tumor types. In the present study RB negative bladder tumors also exhibited strong nuclear p16 staining while each tumor with strong, homogeneous RB nuclear staining were p16 negative, supporting our hypothesis. To expand on these immunohistochemical studies additional cases were selected in which the status of the p16 encoding gene had been determined at the molecular level. Absent p16 and high RB protein expression was found in the tumors having loss of heterozygosity within 9p21 and a structural change (mutation or deletion) of the remaining p16 encoding gene allele, confirming the staining results. These results strongly support the hypothesis that the RB nuclear overexpression recently associated with poor prognosis in bladder cancer is also associated with loss of p16 function and implies that loss of p16 function could be equally deleterious as RB loss in bladder and likely other cancers. (+info)
Expression of vascular endothelial growth factor in human oral squamous cell carcinoma: its association with tumour progression and p53 gene status.
AIMS: To correlate vascular endothelial growth factor (VEGF) expression in oral squamous cell carcinoma with the clinicopathological characteristics and prognosis; and to assess whether p53 gene status is associated with VEGF expression in human cancers. METHODS: Tumour specimens from 45 patients with oral squamous cell carcinomas were examined. Expression of VEGF was determined using an immunohistochemical method, and a tumour was considered positive when more than 5% of the neoplastic cells showed VEGF immunoreactivity. The p53 gene status was screened using a polymerase chain reaction--single strand conformation polymorphism analysis. RESULTS: VEGF positive staining was detected in 19 (42.2%) of the 45 cases. VEGF immunoreactivity did not correlate with the histological degree of tumour differentiation, clinical stages, or lymph node metastasis. The patients with VEGF positive tumours had a significantly worse prognosis than those with VEGF negative tumours. The five year overall survival rate of the VEGF negative patients was 76.5%, as compared with 48.8% for the VEGF positive patients. No significant association between VEGF expression and the p53 gene status of the tumours was found. CONCLUSIONS: VEGF is a good prognostic indicator of the survival of patients with oral squamous cell carcinoma. The p53 gene status does not seem to be associated with VEGF expression in these cancers. (+info)
The role of alternative splicing of the adhesion molecule, CD44, in lymphoid malignancy.
AIM: To investigate the expression of CD44 isoforms containing variant exon 6 (v6) in a well characterised cohort of patients with non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), and to correlate this with phenotype and disease course. METHODS: Cryostat sections of OCT embedded diagnostic nodal material from NHL patients and cryopreserved mononuclear preparations from CLL patients were used as sources of RNA. After reverse transcription, PCR was carried out with amplimers positioned at either side of the variant exon insertion site to amplify all possible CD44 isoforms. Those isoforms containing v6 were identified after Southern blotting and hybridisation with a radiolabelled oligonucleotide. RESULTS: Of 32 NHL samples analysed, 16 did not express CD44 isoforms containing v6, six expressed an isoform containing exon v6 alone, and 10 expressed v6 long isoforms which contained exon v6 in addition to other variant exons. These data did not correlate with lymphoma classification, disease staging, or the presence or absence of extranodal disease. However, those patients expressing v6 long CD44 isoforms had a worse overall survival than those that did not. The plateau of the survival curves was 50% compared with 82%. No v6 long isoforms were detected in the 21 CLL samples investigated. CONCLUSIONS: The expression of v6 long CD44 isoforms is associated with aggressive disease in NHL, independent of grade, stage, or presence of extranodal disease. (+info)
Is hospital care involved in inequalities in coronary heart disease mortality? Results from the French WHO-MONICA Project in men aged 30-64.
OBJECTIVES: The goal of the study was to assess whether possible disparities in coronary heart disease (CHD) management between occupational categories (OC) in men might be observed and contribute to the increasing inequalities in CHD morbidity and mortality reported in France. METHODS: The data from the three registers of the French MONICA Collaborative Centres (MCC-Lille, MCC-Strasbourg, and MCC-Toulouse) were analysed during two period: 1985-87 and 1989-91. Acute myocardial infarctions and coronary deaths concerning men, aged 30-64 years, were included. Non-professionally active and retired men were excluded. Results were adjusted for age and MCC, using a logistic regression analysis. RESULTS: 605 and 695 events were analysed for 1985-87 and 1989-91, respectively. Out of hospital cardiac arrests, with or without cardiac resuscitation, and 28 day case fatality rates were lower among upper executives in both periods. A coronarography before the acute event had been performed more frequently in men of this category and the proportion of events that could be hospitalised was higher among them. In both periods, the management of acute myocardial infarctions in hospital and prescriptions on discharge were similar among occupational categories. CONCLUSIONS: For patients who could be admitted to hospital, the management was found to be similar among OCs, as was the 28 day case fatality rate among the hospitalised patients. In contrast, lower prognosis and higher probability of being hospitalised after the event among some categories suggest that pre-hospital care and the patient's conditions before the event are the primary factors involved. (+info)
Correlation between the status of the p53 gene and survival in patients with stage I non-small cell lung carcinoma.
The association of p53 abnormalities with the prognosis of patients with non-small cell lung carcinoma (NSCLC) has been extensively investigated to date, however, this association is still controversial. Therefore, we investigated the prognostic significance of p53 mutations through exons 2 to 11 and p53 protein expression in 103 cases of stage I NSCLC. p53 mutations were detected in 49 of 103 (48%) tumors. Two separate mutations were detected in four tumors giving a total of 53 unique mutations in 49 tumors. Ten (19%) of mutations occurred outside exons 5-8. Positive immunohistochemical staining of p53 protein was detected in 41 of 103 (40%) tumors. The concordance rate between mutations and protein overexpression was only 69%. p53 mutations, but not expression, were significantly associated with a shortened survival of patients (P<0.001). Furthermore, we investigated the correlation between the types of p53 mutations and prognosis. p53 missense mutations rather than null mutations were associated with poor prognosis (P < 0.001 in missense mutations and P=0.243 in null mutations). These results indicated that p53 mutations, in particular missense mutations, rather than p53 expression could be a useful molecular marker for the prognosis of patients with surgically resected stage I NSCLC. (+info)
Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors.
OBJECTIVE: This study aimed to evaluate the long-term results of treatment and prognostic factors in patients with intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Recent studies have demonstrated the usefulness of re-resection, transarterial oily chemoembolization (TOCE), or percutaneous ethanol injection therapy (PEIT) in selected patients with intrahepatic recurrent HCC. The overall results of a treatment strategy combining these modalities have not been fully evaluated, and the prognostic factors determining survival in these patients remain to be clarified. METHODS: Two hundred and forty-four patients who underwent curative resection for HCC were followed for intrahepatic recurrence, which was treated aggressively with a strategy including different modalities. Survival results after recurrence and from initial hepatectomy were analyzed, and prognostic factors were determined by univariate and multivariate analysis using 27 clinicopathologic variables. RESULTS: One hundred and five patients (43%) with intrahepatic recurrence were treated with re-resection (11), TOCE (71), PEIT (6), systemic chemotherapy (8) or conservatively (9). The overall 1-year, 3-year, and 5-year survival rates from the time of recurrence were 65.5%, 34.9%, and 19.7%, respectively, and from the time of initial hepatectomy were 78.4%, 47.2%, and 30.9%, respectively. The re-resection group had the best survival, followed by the TOCE group. Multivariate analysis revealed Child's B or C grading, serum albumin < or = 40 g/l, multiple recurrent tumors, recurrence < or = 1 year after hepatectomy, and concurrent extrahepatic recurrence to be independent adverse prognostic factors. CONCLUSIONS: Aggressive treatment with a multimodality strategy could result in prolonged survival in patients with intrahepatic recurrence after curative resection for HCC. Prognosis was determined by the liver function status, interval to recurrence, number of recurrent tumors, any concurrent extrahepatic recurrence, and type of treatment. (+info)
Surgery-related factors and local recurrence of Wilms tumor in National Wilms Tumor Study 4.
OBJECTIVE: To assess the prognostic factors for local recurrence in Wilms tumor. SUMMARY BACKGROUND DATA: Current therapy for Wilms tumor has evolved through four studies of the National Wilms Tumor Study Group. As adverse prognostic factors were identified, treatment of children with Wilms tumor has been tailored based on these factors. Two-year relapse-free survival of children in the fourth study (NWTS-4) exceeded 91%. Factors once of prognostic import for local recurrence may lose their significance as more effective therapeutic regimens are devised. METHODS: Children evaluated were drawn from the records of NWTS-4. A total of 2482 randomized or followed patients were identified. Local recurrence, defined as recurrence in the original tumor bed, retroperitoneum, or within the abdominal cavity or pelvis, occurred in 100 children. Using a nested case-control study design, 182 matched controls were selected. Factors were analyzed for their association with local failure. Relative risks and 95% confidence intervals were calculated, taking into account the matching. RESULTS: The largest relative risks for local recurrence were observed in patients with stage III disease, those with unfavorable histology (especially diffuse anaplasia), and those reported to have tumor spillage during surgery. Multiple regression analysis adjusting for the combined effects of histology, lymph node involvement, and age revealed that tumor spillage remained significant. The relative risk of local recurrence from spill was largest in children with stage II disease. The absence of lymph node biopsy was also associated with an increased relative risk of recurrence, which was largest in children with stage I disease. The survival of children after local recurrence is poor, with an average survival rate at 2 years after relapse of 43%. Survival was dependent on initial stage: those who received more therapy before relapse had a worse prognosis. CONCLUSIONS: This study has demonstrated that surgical rupture of the tumor must be prevented by the surgeon, because spills produce an increased risk of local relapse. Both local and diffuse spills produce this risk. Stage II children with local spill appear to require more aggressive therapy than that used in NWTS-4. The continued critical importance of lymph node sampling in conjunction with nephrectomy for Wilms tumor is also established. Absence of lymph node biopsy may result in understaging and inadequate treatment of the child and may produce an increased risk of local recurrence. (+info)
Cardiovascular disease in insulin dependent diabetes mellitus: similar rates but different risk factors in the US compared with Europe.
BACKGROUND: Cardiovascular disease (CVD) in insulin dependent diabetes mellitus (IDDM) has been linked to renal disease. However, little is known concerning international variation in the correlations with hyperglycaemia and standard CVD risk factors. METHODS: A cross-sectional comparison was made of prevalence rates and risk factor associations in two large studies of IDDM subjects: the Pittsburgh Epidemiology of Diabetes Complications Study (EDC) and the EURODIAB IDDM Complications Study from 31 centres in Europe. Subgroups of each were chosen to be comparable by age and duration of diabetes. The EDC population comprises 286 men (mean duration 20.1 years) and 281 women (mean duration 19.9 years); EURODIAB 608 men (mean duration 18.1 years) and 607 women (mean duration 18.9 years). The mean age of both populations was 28 years. Cardiovascular disease was defined by a past medical history of myocardial infarction, angina, and/or the Minnesota ECG codes (1.1-1.3, 4.1-4.3, 5.1-5.3, 7.1). RESULTS: Overall prevalence of CVD was similar in the two populations (i.e. men 8.6% versus 8.0%, women 7.4% versus 8.5%, EURODIAB versus EDC respectively), although EDC women had a higher prevalence of angina (3.9% versus 0.5%, P < 0.001). Multivariate modelling suggests that glycaemic control (HbA1c) is not related to CVD in men. Age and high density lipoprotein cholesterol predict CVD in EURODIAB, while triglycerides and hypertension predict CVD in EDC. For women in both populations, age and hypertension (or renal disease) are independent predictors. HbA1c is also an independent predictor-inversely in EURODIAB women (P < 0.008) and positively in EDC women (P = 0.03). Renal disease was more strongly linked to CVD in EDC than in EURODIAB. CONCLUSIONS: Despite a similar prevalence of CVD, risk factor associations appear to differ in the two study populations. Glycaemic control (HbA1c) does not show a consistent or strong relationship to CVD. (+info)