Hospital General Universitari dAlacant

Alicante, Spain

Hospital General Universitari dAlacant

Alicante, Spain
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Ortiz-Martinez F.,Hospital General Universitari dAlacant | Perez-Balaguer A.,Hospital General Universitari dAlacant | Ciprian D.,Hospital General Universitari dAlacant | Andres L.,Hospital Of Cruces | And 6 more authors.
Human Pathology | Year: 2014

Osteopontin, a secreted phosphoglycoprotein, promotes tumor progression through binding to integrins and CD44 cell receptors. Its overexpression has been correlated with metastasis and adverse outcome in several neoplasms. In breast carcinoma, osteopontin mRNA and its splicing variant-c, a suggested marker for transformed cells, have not been extensively analyzed. Immunohistochemistry was performed in 415 breast carcinomas to examine total osteopontin and osteopontin-c protein distribution. RNA was extracted and retrotranscribed to cDNA from 309 tumors classified into immunophenotypes and in six cell lines representing the breast cancer subtypes. Total osteopontin and osteopontin-c mRNA levels were measured by quantitative RT-polymerase chain reaction. The median fold change of total osteopontin mRNA was higher in HER2-positive (fold-change = 14.7) and triple-negative/basal-like (fold-change = 14.7) tumors, whereas osteopontin-c mRNA was elevated in triple-negative/basal- like subtype (fold-change = 2.8). Total osteopontin levels were increased in SK-BR-3 (HER2-positive) and MDA-MB-468 (triple-negative/basal-like) cell lines. Higher total and osteopontin-c mRNA levels were seen in tumors of high grade, with necrosis, positive nodal status and high Nothingam Prognostic Index score. Disease-free survival was significantly shorter for patients whose tumors overexpressed total osteopontin (67% vs 73%). Moreover, increased osteopontin-c stratified subgroups of patients at higher risk of recurrence among immunophenotypes, especially in triple-negative/basal-like subtype (70% vs 83%). By multivariate analyses for disease-free survival, osteopontin-c emerged as a significant predictor of relapse. In summary, our data showed an association of osteopontin with poor prognostic factors, aggressive subtypes HER2 and triple-negative/basal-like, and higher risk of recurrence. © 2014 Elsevier Inc. All rights reserved.

Peiro G.,Hospital General Universitari dAlacant | Adrover E.,Hospital General Universitari dAlacant | Sanchez-Tejada L.,Hospital General Universitari dAlacant | Lerma E.,Hospital Of La Santa Creu I Sant Pau | And 5 more authors.
Modern Pathology | Year: 2011

The biology of breast carcinoma shows a great variation, reflected by the recent classification of phenotypes based on DNA microarrays or immunohistochemistry. The aim of this study was to determine the prevalence of insulin-like growth factor-1 receptor (IGF1R) in breast carcinoma subtypes and the impact on the outcome. We studied 197 consecutive breast carcinoma patients in stage I-II treated conservatively. Phenotypes were assessed on the basis of the expressions of ER/PR, HER2, Ki67, p53, Bcl2, CK5/6 and EGFR. Moreover, IGF1R expression (α-subunit and Β-phosphorylated/active form) was evaluated by immunohistochemistry, IGF1R mRNA levels by quantitative RT-PCR and IGF1R mutations by direct DNA sequencing. Overall, 40% (78/197) of tumors were luminal A, 24% (48/197) luminal B, 19% (37/197) HER2-positive and 17% (34/197) basal/triple-negative. Luminal A tumors were predominantly of low grade, without necrosis, presenting in older patients as a ≤2-cm unilateral mass (all ≤P0.046). α-IGF1R overexpression was observed more frequently in luminal A (49%) cases, followed by luminal B (20%), HER2-positive area under the curve (22%) and basal/triple-negative cases (9%) (P0.01) with similar results for mRNA levels (53, 24, 13 and 10%, respectively) (P0.038), but without differences for mutations (PNS). High IGF1R mRNA correlated with poor patient survival among subtypes (P0.004) (Kaplan-Meier; log-rank test). For overall survival, only histological grade and IGF1R mRNA emerged as significant predictors (P≤0.034; Cox regression). Increased IGF1R mRNA implies poorer patient prognosis among the different subtypes, and that may be associated with the lack of responsiveness to tamoxifen in cases with a positive hormone receptor status. Our results highlight the biological and clinical relevance of IGF1R in early breast carcinoma subtypes, and provide knowledge to assist in treatment decision. © 2011 USCAP, Inc.

Montserrat N.,Autonomous University of Barcelona | Gallardo A.,Autonomous University of Barcelona | Escuin D.,Autonomous University of Barcelona | Catasus L.,Autonomous University of Barcelona | And 5 more authors.
Human Pathology | Year: 2011

It has been suggested that down-regulation of E-cadherin in invasive breast ductal carcinomas is mediated by the aberrant expression of several of its transcriptional repressors, but their inhibitory role and clinical importance are not yet well established. We investigated gene and protein expression patterns of the E-cadherin repressors SNAIL, ZEB1, and TWIST in relation to clinicopathologic parameters, in a series of 88 patients with invasive breast ductal carcinomas. Up-regulation of SNAIL messenger RNA (P = .008) and down-regulation of TWIST (P = .022) were associated with triple-negative tumors, whereas ZEB1 gene expression was more frequent in hormone-positive tumors (P = .004). Loss of E-cadherin was found in 19% of the tumors, but it did not correlate with aberrant expression of any of the repressors investigated herein. Nonetheless, we found that ZEB-1 protein overexpression inversely correlated with high tumor grade (P = .018), nuclear grade (P = .002), and presence of lymph nodes (P = .001), and these data were consistent with the gene expression data for ZEB1. Clinically, down-regulation of ZEB1 messenger RNA was associated with poor overall survival (P = .011) and disease-free survival (P = .053), whereas patients with TWIST negative tumors had a worse overall survival (P = .008) and disease-free survival (P = .006). Our data indicate that deregulation of TWIST is somehow important in the aggressiveness of triple-negative carcinomas and poor patient outcome, whereas down-regulation of ZEB1 seems to play a role in tumor spread, metastases, and poor survival. © 2011 Elsevier Inc. All rights reserved.

Objective: To compare the construct validity of three functional capacity questionnaires in patients with fibromyalgia. Patients and methods: Transversal multicentric study of 301 patients from fifteen rheumatology outpatient clinics in Spain. Scores of Health Assessment Questionnaire (HAQ), Fibromyalgia Health Assessment Questionnaire (FHAQ) and the physical function scale of the Fibromyalgia Impact Questionnaire (PF-FIQ) were compared with extreme groups of patients defined by four external indirect measures: 6 Min Walk Test, a modified Borg Fatigue Scale, Lumbar Spine Flexion Test and Patient Global Passive Mobility Assessment. Standardized differences were determined and correlation coefficients were calculated between the three questionnaires scores. Results: All three questionnaires showed good construct validity, but the results obtained with the PF-FIQ were poorer. Correlations between HAQ and FHAQ were very high (0.92), but correlations between these two questionnaires and PF-FIQ were only moderate (0.59). Conclusions: HAQ and FHAQ are more valid measures of functional capacity than the PF-FIQ. HAQ could be substituted by FHAQ in some settings because of its shorter format (only 8 items). © 2009 Elsevier España, S.L. All rights reserved.

Rivera J.,Hospital General Universitario Gregorio Maranon | Esteve-Vives J.,Hospital General Universitari dAlacant | Vallejo M.A.,Spanish University for Distance Education (UNED) | Rejas J.,Pfizer
Rheumatology International | Year: 2011

Temporary work disability (TWD) is more common in patients with fibromyalgia (FM) than among the rest of the workers. To describe the differences between patients who take sick leave (TWD group) and those who continue to work regularly (control group). To determine what factors are associated with TWD. Multicentre, cross-sectional study with a cohort of patients with FM seen in rheumatology clinics throughout Spain. The following information was recorded: demographic data, clinical manifestations, comorbidities, health self-perception, emotional issues, functional capacity, physical function tests, utilization of healthcare resources, TWD during the past 12 months, and quitting paid employment due to the disease. Descriptive statistics was used to compare variables between the TWD group and the control group. A logistic regression analysis was done to determine which factors are associated with TWD. The study cohort was composed of 301 patients with FM (women: 96.7%) with a mean age of 48.7 ± 8.5 years and a disease duration of 11.5 ± 9.1 years. There were 56.8% active workers, of whom 67.8% had had some TWD. The mean TWD length was 44 ± 69.6 days/year. TWD correlated significantly with sedentary work, clinical manifestations, comorbidities, self-perceived health, poor functional capacity, physical function, and healthcare resource utilization. The factors independently associated with TWD are sedentary work, more clinical manifestations, fatigue, and poor flexibility. Of the cases of people who quit their jobs, 66.9% were associated with FM. TWD in patients with FM is associated with sedentary work, a worse clinical situation, and worse functional capacity. © 2010 Springer-Verlag.

Rivera J.,Hospital General Universitario Gregorio Maranon | Rejas-Gutierrez J.,Pfizer | Vallejo M.A.,Spanish University for Distance Education (UNED) | Esteve-Vives J.,Hospital General Universitari dAlacant | De Salas-Cansado M.,Pfizer
Clinical and Experimental Rheumatology | Year: 2012

Objective: To estimate the burden and to prospectively analyse resources utilisation and costs in a cohort of treated patients with fibromyalgia (FM) in daily practice. Methods: Prospective, observational, multicentre, 3-month study in 232 patients with FM according to the ACR criteria (98% women, 47 years), with no concomitant systemic diseases, followed in rheumatology units. The control group consisted of 110 subjects without FM or any other systemic condition, paired by age and gender. Clinical assessment, use of healthcare resources and treatments, out-of-pocket expenses, occupational status, days off work, and calculation of lost workdays equivalents were recorded. Results: Patients had worse clinical status, four times the control group's healthcare costs, twelve times its indirect costs and six times its total costs. After the treatment, there was significant clinical improvement in the patient group, the healthcare costs were significantly reduced in all components except for drugs costs, which increased (p<0.001), and out-of-pocket expenses, which remained unaltered. Indirect costs were reduced (p<0.05) in the FM group only, mainly due to fewer days off work. The patient group presented a significantly greater variation in montly total costs than the controls;-€193.75 ± 781.9 vs. -€26.22 ± 402.7, p=0.006. The patients who most reduced their healthcare costs were actively employed. Conclusions: Treated patients with FM in daily practice improved their clinical status and were accompanied by a significant reduction in the cost of the illness. The extra cost of drugs is substantially compensated for by less use of other healthcare resources and fewer days off work. © Clinical and Experimental Rheumatology 2012.

Vallejo M.A.,Spanish University for Distance Education (UNED) | Rivera J.,Hospital Universitario Gregorio Maranon | Esteve-Vives J.,Hospital General Universitari dAlacant | Rodriguez-Munoz M.F.,Spanish University for Distance Education (UNED)
Revista de Psiquiatria y Salud Mental | Year: 2012

Introduction: The HADS is a questionnaire widely used to evaluate anxiety and depression, although its use in fibromyalgia patients has not yet been reported. The aim of this study is to know the usefulness of the HADS to evaluate the emotional aspects related to fibromyalgia patients. Methods: This paper studies a sample of 301 fibromyalgia patients. The scientific goodness of the questionnaire is analyzed, and its structure is compared with other models by confirmatory factor analysis. Two external severity indices are used, number of tender points and patient's employment situation. Results: The results show higher levels of anxiety than in other disorders, adequate reliability and a three-factor model with better statistical fit. Nevertheless, this structure was not shown more useful than the two-factor structure for the external criteria studied. Conclusions: The HADS has been shown to be a useful tool for exploring the presence of anxiety and depression in fibromyalgia patients and that the number of tender points does not seem to be related to the severity of the psychological aspects measured by the HADS in our sample, while there does seem to be a correspondence between psychological condition and absence from work. © 2011 SEP y SEPB. Published by Elsevier España, S.L. All rights reserved.

Vallejo M.A.,Spanish University for Distance Education (UNED) | Rivera J.,Hospital Universitario Gregorio Maranon | Esteve-Vives J.,Hospital General Universitari dAlacant | Rejas J.,Pfizer
Health and Quality of Life Outcomes | Year: 2011

Background: Fibromyalgia (FM) is a complex syndrome that affects many aspects of the patients life and it is very difficult to evaluate in clinical practice. A recent study has developed the Combined Index of Severity of Fibromyalgia (ICAF), an instrument that evaluates diverse aspects of FM and offers five indices: emotional, physical, active coping, passive coping and total. The objective of this study is to confirm the structure of the ICAF, check its test-retest reliability, assess its sensitivity to change, and compare the results obtained in a sample of patients with fibromyalgia with another sample of healthy controls.Methods: A total of 232 patients took part in the study, 228 women and 4 men, with a mean age of 47.73 years of age (SD = 8.61) and a time of disease evolution since diagnosis of 4.28 years (SD = 4.03). The patients from the FM group completed the ICAF. Between one and two weeks later, they again attended the clinic and complete the 59 items on the ICAF (retest) and immediately afterwards they began treatment (according to daily clinical practice criteria). A sample of healthy subjects was also studied as a control group: 110 people were included (106 women and 4 men) with a mean age of 46.01 years of age (SD = 9.35). The study was conducted in Spain.Results: The results obtained suggest that the four-factor model obtained in the previous study adequately fits the data obtained in this study. The test-retest reliability and internal consistency were all significant and show a high degree of correlation for all the factors as well as in overall score. With the exception of the passive coping factor, all the other scores, including the overall score, were sensitive to change after the therapeutic intervention. The ICAF scores of the patients with fibromyalgia compared with those of the control group were markedly different.Conclusions: The findings suggest that the ICAF is a valid, reliable, sensitive to change instrument with the added advantage that it offers some additional domains (factors) that provide very valuable information regarding the most delicate aspects of the patient, which must be addressed at the time of treatment in daily clinical practice. © 2011 Vallejo et al; licensee BioMed Central Ltd.

Vallejo M.A.,Spanish University for Distance Education (UNED) | Rivera J.,Hospital Universitario Gregorio Maranon | Esteve-Vives J.,Hospital General Universitari dAlacant
Health and Quality of Life Outcomes | Year: 2010

Background: Fibromyalgia is a syndrome with heterogeneous symptoms. The evaluation in the clinical setting usually fails to cover the complexity of the syndrome. This study aims to determine how different aspects of fibromyalgia are inter-related when measured by means of a self-reporting tool. The objective is to develop a more complete evaluation model adjusted to the complexity and multi-dimensional nature of the syndrome.Methods: Application was made of the Fibromyalgia Impact Questionnaire, the Hospital Anxiety and Depression Scale, the Brief Pain Inventory, the Fatigue Assessment Scale, the Health Assessment Questionnaire, the General Health Questionnaire (GHQ-28), the Chronic Pain Coping Inventory, the Arthritis Self-efficacy Scale and the Sleep Quality Scale. An assessment was made, on the basis of clinical interviews, case histories and specific tests, of the patient sociodemographic data, comorbidity, physical exploration and other clinical indexes. An exploratory factor analysis was made, with comparisons of the clinical index scores in extreme groups of patients.Results: The ICAF composed of 59 items was obtained, offering four factors that explain 64% of the variance, and referred to as Emotional Factor (33.7%), Physical-Activity (15%), Active Coping (9%) and Passive Coping (6.3%). A t-test between the extreme scores of these factors in the 301 patients revealed statistically significant differences in occupational status, medically unexplained syndromes, number of tender points, the six-minutes walk test, comorbidity and health care costs.Conclusions: This study offers a tool allowing more complete and rapid evaluation of patients with fibromyalgia. The test intrinsically evaluates the emotional aspects: anxiety and depression, and their impact upon social aspects. It also evaluates patient functional capacity, fatigue, sleep quality, pain, and the way in which the patient copes with the disease. This is achieved by means of a self-assessment questionnaire based on elements from well known tests. © 2010 Vallejo et al; licensee BioMed Central Ltd.

Peiro G.,Hospital General Universitari dAlacant | Peiro F.M.,Hospital Marina Baixa | Ortiz-Martinez F.,Hospital General Universitari dAlacant | Planelles M.,Hospital Virgen Of Los Lirios | And 5 more authors.
Human Pathology | Year: 2013

The classification of endometrial carcinoma divided into types I and II has shown clinical usefulness. Molecular alterations of PTEN and Wnt/β-catenin have been identified in this neoplasia. However, the role of mammalian target of rapamycin according to subcellular localization in the pathogenesis of this neoplasia and its prognostic significance are not well defined. We studied the expression of phosphorylated mammalian target of rapamycin, PTEN, and β-catenin and their relationship with clinicopathologic features, molecular factors (microsatellite instability, mismatch repair, and BRAF genes) and patients' survival in a series of 260 nonconsecutive endometrial carcinomas. Tissue microarrays were manually constructed, and genomic DNA was extracted from paraffin-embedded cylinders (1 mm thick) from preselected tumor areas. The mammalian target of rapamycin in the nuclei (mTORC2; 47%) or cytoplasm (mTORC1; 48%) were seen in type II endometrial carcinoma, the latter also in advanced stages (P ≤.046). PTEN loss (58%) was detected in type I endometrial carcinoma of grade 1, at early stage, with mismatch repair gene loss (24.4%) and microsatellite instability-positive status (22%; P ≤.05). Nuclear β-catenin (16%) was found in type I tumors of younger patients (P ≤.003). In contrast, BRAF-V600E mutations were not detected (0%). Mammalian target of rapamycin cytoplasmic high expression implied poorer prognosis (P =.02; Kaplan-Meier, log-rank test), but grade 3 tumors, vascular invasion, advanced stage, or PTEN presence correlated independently with a negative impact on survival (all P ≤.036; Cox analysis). Our results show that mammalian target of rapamycin, PTEN, and β-catenin are independently involved in different molecular subtypes of endometrial carcinoma with diverse patients' prognosis and support their distinctive treatment based on targeted drugs. © 2013 Elsevier Inc.

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