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M Fraga

Publications and source records attributed to M Fraga.

At least 19 recordsLinked to original sources
PubMed2006

HER-2 status determination in breast carcinomas. A practical approach.

Accurate evaluation of HER-2 status is crucial in the selection of breast carcinoma patients for trastuzumab (Herceptin) treatment. Various laboratory methods have been used for this purpose. The aim of the present work was to analyse the results obtained in the routine practice by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in determination of HER-2 status. Five hundred and three cases of breast invasive ductal carcinoma were selected to analyse the HER-2 overexpression by immunohistochemistry (HercepTest, Dako). HercepTest 2+ equivocal cases (60) were studied by FISH (PathVysion, Vysis) to determine HER-2 gene amplification. HER-2 overexpression determined by Herceptest was shown in 97/503 cases (19%). FISH performed on equivocal cases demonstrated HER-2 amplification in 11/60 tumours (18%). IHC and FISH together showed HER-2 overexpression/gene amplification in 21% of breast invasive carcinomas. Immunohistochemical determination of HER-2 status represents an easy and standardized method that (in contrast to FISH) can be performed in all pathology laboratories without need of any special microscope and enabling to check the morphologic features of the cells analysed. However, in order to assure the reliability of the results, standardization of fixation protocols, automation of the immunohistochemical procedure, and training of pathologists in the interpretation of the results (scoring criteria) should be a priority. Equivocal HercepTest cases must be analysed by FISH preferably in a reference laboratory.

Antibodies, Monoclonal↗
PubMed2005

Large B-cell lymphoma with Hodgkin's features.

AIMS: To describe the features of a series of nine cases of diffuse large B-cell lymphoma (DLBCL) showing morphological and immunophenotypic features that are intermediate with Hodgkin's lymphoma (HL). METHODS AND RESULTS: Most cases (6/9) presented as mediastinal tumours affecting young males, while the other three cases arose in extramediastinal locations. Histopathologically, tumours showed diffuse large cell areas in a polymorphous background, with pleomorphic cytology and the common presence of Hodgkin's and Reed-Sternberg cells. Immunophenotypically, tumours shared features of DLBCL and classical HL, with expression of CD30, CD15 (6/9), and a full B-cell profile including CD45RB, CD20, CD79a and OCT2. Epstein-Barr virus-latent membrane protein expression was found in 2/9 cases. The majority of tumours had immunohistochemical features consistent with activation of the NF-(kappa)B pathway, including nuclear location of the c-REL/p65 subunit, overexpression of phosphorylated I(kappa)B(alpha), and overexpression of NF-(kappa)B targets. Finally, 2/9 cases showed 3q27 (BCL6) rearrangement, and 1/9 had p53 gene mutations, both of which are rarely detected in classical HL. CONCLUSIONS: These findings suggest that DLBCLs with HL features constitute a distinctive subgroup of aggressive lymphomas whose neoplastic growth and peculiar characteristics could be facilitated by a particular microenvironment found in the mediastinum.

Adult↗
PubMed2005

Cell-cycle-associated markers and clinical outcome in human epithelial cancers: a tissue microarray study.

The development and progression of epithelial cancers are the result of an imbalance in signals promoting and inhibiting cellular proliferation and apoptosis. The aim of this study is to evaluate the expression of cell-cycle and apoptosis regulators and correlate them with clinical outcome in the most frequent carcinomas, in order to establish common prognostic biomarkers independent of cancer origin. Using tissue microarrays (TMAs), we have analysed the immuno-expression of Ki-67, Bcl-2, Bax, cyclin D1, cyclin D3, CDK1, CDK2, CDK6, p16, p21, and p27 in a series of 205 carcinomas of the large bowel, breast, lung and prostate (80, 73, 37 and 15 cases, respectively). By univariate analysis, positivity for p27, p16 and Bcl-2 was associated with better overall survival (P<0.0135, P<0.0442 and P<0.0001, respectively). The risk of mortality was 2.3-fold greater in patients without Bcl-2 expression. TMA immunohistochemical analysis identified a subset of epithelial cancers with overlapping alterations in cell-cycle checkpoints, apoptosis regulators and tumour suppressor pathways. We found that in most common epithelial cancers, regardless of origin, Bcl-2 appears to be the key biological factor influencing clinical behaviour.

Adult↗
PubMed2003

Primary extramedullary myeloid tumor of the breast: a case report and review of the literature.

Primary extramedullary myeloid tumors (PEMMT) are extramedullary proliferations of myeloid cells occurring in the absence of an antecedent myeloproliferative disorder. They have predilection for the skin, lymph nodes, central nervous system, and small intestine. Breast is an uncommon location for PEMMT and only a few cases have been reported so far in the medical literature. Many of these cases have been initially misdiagnosed. We reviewed all the reported cases of PEMMT of the breast in the English-language literature since 1965. In addition, we present a new case of PEMMT of the breast who presented with a mass in her right breast mimicking a breast malignancy and was initially misdiagnosed as non-Hodgkin's lymphoma. A careful histologic examination with immunohistochemical studies revealed the presence of PEMMT of the breast. Treatment with systemic chemotherapy and local radiotherapy rendered a complete remission. Seventeen cases of PEMMT of the breast were reported in the English literature from 1965 to 2003. Most of the cases were misdiagnosed initially as lymphomas, breast carcinomas, or malignant melanomas. PEMMT of the breast is a poorly recognized entity whose diagnosis frequently challenges both the pathologist and the oncologist. Given the small number of patients reported no optimal treatment has been defined, but systemic chemotherapy similar to that given for acute myeloid leukemia with or without local radiotherapy may result in long remissions and avoid the progression to overt acute myeloid leukemia.

Adult↗
PubMed2003

Fatal Kikuchi-Fujimoto disease: the lupus connection.

Kikuchi-Fujimoto disease (KFD) is a histiocytic necrotizing lymphadenitis found mainly in young women. Patients typically present with cervical lymphadenopathy and fever and follow almost always a benign course with excellent outcomes. The etiology of KFD remains unknown and controversial although several viruses have been associated with this disease. One theory proposes that KFD may be a self-limiting form of systemic lupus erythematosus (SLE). This theory is strongly supported by the fact that microscopic features of KFD can be very similar to those found in lupus lymphadenitis. Despite its usually benign course, several cases with fatal outcomes have been reported. We report here a case of clinically aggressive KFD, which featured several autoimmune-related events and resulted in a fatal outcome. Autopsy studies showed characteristic findings of SLE, which suggests a remarkable link between SLE and KFD. Early and intensive immunosuppressive treatment may be the only option for patients who develop very aggressive forms of KFD in order to avoid a fatal outcome.

Adult↗
PubMed2002

T-cell/histiocyte-rich large B-cell lymphoma is a disseminated aggressive neoplasm: differential diagnosis from Hodgkin's lymphoma.

AIMS: An accurate diagnosis of T-cell/histiocyte-rich large B-cell lymphoma needs to take into consideration those forms of Hodgkin's lymphoma also characterized by a predominance of small lymphocytes and histiocytes, i.e. nodular lymphocyte predominance Hodgkin's lymphoma and lymphocyte-rich classical Hodgkin's lymphoma. We have studied the clinical, phenotypic and genetic features of a series of 12 cases of T-cell/histiocyte-rich large B-cell lymphoma along with 18 cases of Hodgkin's lymphoma for comparative purposes. METHODS AND RESULTS: Of the Hodgkin's lymphoma cases, there were 11 lymphocyte predominance type and seven classic type. T-cell/histiocyte-rich large B-cell lymphomas presented usually in advanced stages (III or IV in 11/12 cases), frequently with 'B' symptoms (6/9 cases), and followed a more aggressive course than Hodgkin's lymphoma (4/8 patients died due to the tumour in T-cell/histiocyte-rich large B-cell lymphoma versus 0/15 in Hodgkin's lymphoma). T-cell/histiocyte-rich large B-cell lymphoma cases showed diffuse effacement of the nodal architecture by a proliferation of scattered large atypical B-cells obscured by a background of small T-lymphocytes (more CD8+, TIA1+ than CD57+). Five cases showed also a prominent histiocytic component. The large B-cells expressed CD45 and often EMA (6/10 cases). On the other hand, CD 30, CD15 and latent infection by Epstein-Barr virus (EBV) were generally lacking. bc l6 and CD10 were, respectively, detected in 6/6 and 1/5 cases. Conventional polymerase chain reaction (PCR) showed monoclonal immunoglobulin heavy chain (IgH) gene rearrangements in all T-cell/histiocyte-rich large B-cell lymphomas studied (5/5), but did not detect any case with t(14;18) involving the major breakpoint region (0/4). CONCLUSIONS: The differential diagnosis of T-cell/histiocyte-rich large B-cell lymphoma from Hodgkin's lymphoma is facilitated by the integration of different immunophenotypic, molecular and clinical findings. T-cell/histiocyte-rich large B-cell lymphoma is a monoclonal neoplasm of bc l6+ B-cells with a phenotypic profile similar to lymphocyte predominance Hodgkin's lymphoma, suggesting a germinal centre origin and a possible relation to this disease. Therefore, in order to distinguish it from lymphocyte predominance Hodgkin's lymphoma, characterization of the reactive background, IgH gene rearrangement studies by conventional PCR and clinical features are more useful. In contrast, T-cell/histiocyte-rich large B-cell lymphoma can be distinguished from classical Hodgkin's lymphoma thanks to the presence of monoclonal IgH rearrangement and the CD 30-CD15-CD45+EMA+ immunophenotypic profile of the neoplastic cells in T-cell/histiocyte-rich large B-cell lymphoma.

Adult↗
PubMed2001

Primary cutaneous large B-cell lymphoma: the relation between morphology, clinical presentation, immunohistochemical markers, and survival.

The histogenesis, morphology, immunophenotype, and clinical behavior of cutaneous large B-cell lymphomas (CLBCL) are largely a matter of controversy. We performed an investigation to determine whether CLBCL have features that differentiate them from other large B-cell lymphomas and whether CLBCL is itself a heterogeneous group. To this end, we reviewed the main characteristics of a series of 32 cases of LBCL found in the skin. We reviewed the clinical findings and paraffin sections of the tumors from these 32 patients. The immunohistochemical study performed included p53, MIB1, Bcl2, Bcl6, and CD10 markers. We carried out statistical analysis of these data (univariate and multivariate), seeking an association between the features of the tumors and clinical outcome, as defined by failure-free survival time. Only one patient died as a consequence of the lymphoma. Nevertheless, the accumulated probability of survival without failure at 48 months was 0.46. The number, type, and localization of the lesions were not associated with variations in either survival or failure-free survival. The expression of p53 was negative in this group of CLBCL, whereas Bcl-2 expression or localization in the lower leg did not relate to any other significant feature. Histologic examination of the cases disclosed three different groups: Grade III follicular lymphomas (FLs), monomorphous large B-cell lymphomas (LBCL type I), and LBCL with an admixed component of small B-lymphocytes (LBCL type II). Grade III FL (11 cases) tended to be found in the head and neck and showed CD10 expression in a majority of cases. A higher probability of lymph node relapses was associated with cases located in the head and neck and with CD10+ tumors. Cutaneous large B-cell lymphomas are indolent tumors, but follow an insidious course. Our data support the interpretation that CLBCL is a heterogeneous condition; comprises some LBCL derived from CD10+ germinal center cells which manifests more frequently as tumors in the head and neck region, with an increased probability of relapse in lymph nodes [1] and has some distinctive morphologic features. The existence of a component of small B-cells within the other CLBCL could lend support to the theory that some of these tumors, more than arise de novo, may have originated in preexistent small B-cell lymphomas, but no firm evidence of this is provided in this study.

Adult↗
PubMed2000

Blastoid NK cell leukemia/lymphoma with cutaneous involvement.

Malignant neoplasms from natural killer (NK) cells are characterized by their positivity for CD56 and absence of monoclonal TCR gene rearrangement. Recently, they have been classified into four main types (nasal and nasal-type NK cell lymphoma, aggressive NK cell leukemia/lymphoma, and blastoid NK cell leukemia/lymphoma), based on clinical features, racial predisposition, presence of azurophilic granules, immunophenotype and association with Epstein-Barr virus (EBV) infection. A 72-year-old Caucasian man presented with a malignant neoplasm comprised of blastoid cells without azurophilic granules in the Giemsa stain, with positivity for CD2, CD4, HLA-DR, CD45 and CD56, and negativity for CD3 (surface and cytoplasmic) and CD5. In situ hybridization for EBV and PCR analysis of rearrangement of the T cell receptor gene were negative. Based on these results, a diagnosis of blastoid NK cell lymphoma was made. In this case the first clinical manifestations were the cutaneous lesions, and, although the disease was already advanced at the diagnosis, the patient responded completely to the treatment and remains asymptomatic 14 months after diagnosis.

Aged↗
PubMed2000

Increased expression of growth hormone and prolactin receptors in hepatocellular carcinomas.

The liver is an essential target tissue for growth hormone (GH) and prolactin (PRL). The aim of this study was to determine the in situ expression of growth hormone receptor (GHR) and prolactin receptor (PRLR) in hepatocellular carcinomas and to compare the results with normal liver. For this purpose, in situ hybridization (ISH) and immunohistochemical techniques were performed and several tests were conducted to validate the results. By radioactive ISH, all the hepatocellular carcinomas studied showed labeling for GHR and PRLR mRNAs. Relative expression levels, determined by computer-assisted microdensity, were higher in hepatocellular carcinomas than in normal liver. Immunohistochemistry led us to confirm the constant expression of both receptor proteins in hepatocellular carcinomas and normal liver and to demonstrate their localization not only in the cytoplasm but also in the nucleus. These results confirm that the liver is a major GH and PRL target tissue and suggest that in hepatocellular carcinomas the proliferative effects of these hormones may be increased by a higher expression of their receptors.

Adult↗
PubMed2000

Epstein-Barr virus-latent membrane protein 1 expression has a favorable influence in the outcome of patients with Hodgkin's Disease treated with chemotherapy.

The effect of molecular factors in the outcome of Hodgkin's Disease (HD) is being currently studied. In a previous series of HD, including patients treated only with radiotherapy and patients treated with chemotherapy (with or without radiotherapy), we found that a high proliferation index had an adverse influence in overall survival (OS) and in the achievement of a complete remission (CR). Loss of Rb expression also had an adverse prognostic influence in achievement of CR. On the other hand LMP1-EBV expression had a favorable influence for OS. The expression of other molecular factors, p53, bcl2 and CD15 did not show prognostic influence. In the present paper we have studied the effect of these molecular variables in 110 patients, of the previous series who had been treated with chemotherapy. A retrospective study was performed in these 110 patients with HD treated with chemotherapy (ABVD or variants, 62%, or regimes not containing adriamycin, 38%) with or without adjutant radiotherapy, collected at the 11 centers belonging to the Spanish Collaborative Group for the Study of Hodgkin's Disease. The prognostic value of clinical variables and the expression of p53, bcl2, CD15, Rb, LMP 1-EBV and proliferative fraction demonstrated with sensitive immunohistochemical methods were studied. Cox's multivariate analysis was performed to assess their influence in failure-free survival (FFS) and OS. A multivariate logistic regression analysis was performed for studying the effect of the variables in the achievement of a CR. Of the clinical variables, only advanced stage (III/IV) had a significant independent adverse influence in FFS, in OS and in the achievement of CR and advanced age in OS. Of the molecular variables, LMP1-EBV had an independent and strong favorable influence in FFS, in OS and in the achievement of CR. Rb expression had a modest favorable influence in CR. The rest of the molecular variables had no independent influence on the outcome of the disease. In conclusion these results confirm the favorable prognostic value of LMP1-EBV expression in the subset of patients with HD treated with chemotherapy.

Analysis of Variance↗
PubMed1999

Primary anaplastic large cell lymphoma of the central nervous system.

Central nervous system (CNS) involvement is extremely rare in anaplastic large cell lymphoma (ALCL), and in children only isolated cases have been reported, mainly as secondary CNS involvement. A case of fatal primary ALCL of the brain in a 13-year-old white boy is reported. Magnetic resonance imaging of the brain showed decreased absorption in T1- and T2-weighted image showed a hyperintense signal in the right parietal lobe and 2 masses in the right frontal lobe. A frontal lobe biopsy showed a pleomorphic neoplasm diffusely infiltrating the brain parenchyma and composed of large cells with bizarre, often polylobated or horseshoe-shaped nuclei. Immunohistochemical stains showed diffuse strong positivity for CD30, anaplastic lymphoma kinase protein (ALK-1), p80, leucocyte common antigen, CD45RO (UCHL1), and focal staining for epithelial membrane antigen. Immunostainings for cytokeratins, monocyte-macrophage, and B-cell markers were negative. Epstein-Barr virus latent membrane protein was not detected. To the best of our knowledge, there is only 1 case of primary ALCL of the brain in childhood previously reported in the literature. Before the biopsy, both cases were clinically misdiagnosed as mycobacterial CNS infection. Therefore, primary ALCL should also be included in the differential diagnosis when a mycobacterial CNS infection is suspected in pediatric patients; a careful cytological evaluation of the cerebrospinal fluid or cerebral biopsy are essential for an accurate diagnosis.

Adolescent↗
PubMed1999

Biofilter performance and characterization of a biocatalyst degrading alkylbenzene gases.

A biofilter treating alkylbenzene vapors was characterized for its optimal running conditions and kinetic parameters. Kinetics of the continuous biofilter were compared to batch kinetic data obtained with biofilm samples as well as with defined microbial consortia and with pure culture isolates from the biofilter. Both bacteria and fungi were present in the bioreactor. Five strains were isolated. Two bacteria, Bacillus and Pseudomonas, were shown to be dominant, as well as a Trichosporon strain which could, however, hardly grow on alkylbenzenes in pure culture. The remaining two strains were most often overgrown by the other three organisms in liquid phase batch cultures. mu max, KS, KI values and biodegradation rates were calculated and compared for the different mixed and pure cultures. Since filter bed acidification was observed during biofiltration studies reaching a pH of about 4, experiments were also undertaken to study the influence of pH on performance of the different cultures. Biodegradation and growth were possible in all cases, over the pH range 3.5-7.0 at appreciable rates, both with mixed cultures and with pure bacterial cultures. Under certain conditions, microbial activity was even observed in the presence of alkylbenzenes down to pH 2.5 with mixed cultures, which is quite unusual and explains the ability of the present biocatalyst to remove alkylbenzenes with high efficiency in biofilters under acidic conditions.

Bacillus↗
PubMed1999

[Impact of Spanish publications on foreign anesthesiology journals].

OBJECTIVE: To analyze the number of articles by Spanish authors in three international anesthesiology journals and assess the impact of Spanish anesthesiology literature during the same period by way of citations. MATERIAL AND METHODS: Articles published in Anesthesiology, British Journal of Anesthesiology (BJA) and Anesthesia & Analgesia (Anesth Analg) during 1997 were reviewed. We collected the following data: type of document, country of origin of the authors, total number of references, number of citations of Spanish articles and the journals from which they were cited. Later, the Spanish contribution was compared to that of other countries of the European Union, with data considered in function of Gross National Product per capita (GNPpc) of each country. RESULTS: The incidence of Spanish articles published in Anesthesiology, BJA and Anesth Analg was 0.37%, 0.71% and 0.9%, respectively. The production of Spanish documents in function of GNPpc ranked Spain in the tenth position in Anesthesiology, eleventh in BJA and sixth in Anesth Analg. Of the total number of citations, 143 (0.4%) were of Spanish publications. In Spanish articles in Anesthesiology the percentage of Spanish citations was 11%, in BJA the figure was 44% and in Anesth Analg it was 13%. Finally, over 90% of the Spanish articles cited in Anesthesiology and in Anesth Analg were published in English in foreign journals. CONCLUSIONS: The number of Spanish articles published in Anesthesiology, BJA, and Anesth Analg is low, although the comparison of our productivity with that of other EU countries in function of GNPpc places us in an intermediate position. The impact of Spanish literature on international studies is low, particularly research published in Spanish national journals, a circumstance that is reflected even in articles published by Spanish authors.

Anesthesiology↗
PubMed1999

[Comparison of sevoflurane and propofol in the maintenance of and recovery from anesthesia].

OBJECTIVE: To compare the recovery of patients after anesthesia with sevoflurane or propofol during open urological surgery or lumbar column surgery of intermediate duration. PATIENTS AND METHODS: Thirty-six ASA I, II or II patients were enrolled prospectively and randomly assigned to two groups to receive either sevoflurane (n = 19) or proporol (n = 17). Anesthetic induction was accomplished with thiopental, fentanil and vecuronium. During anesthetic maintenance a mixture of 60% nitrous oxide in oxygen plus the drug under study was adjusted to keep blood pressure and/or heart rate within +/- 20% of baseline. After surgery we recorded time until eye opening, spontaneous breathing, extubation, orientation, and identification of parts of the body. Side effects were likewise recorded. In the postanesthetic recovery ward patient condition was assessed using the Aldrete scale, the Newman-Trieger test and a visual analog scale for postoperative pain. Consumption of analgesic during the first 24 h after surgery was monitored. RESULTS: No significant differences were found in demographic data; duration of anesthesia; anesthetic doses; or time until spontaneous breathing, extubation, orientation or identification of parts of the body. Only time until eye opening was shorter in the sevoflurane group than in the propofol group (6.9 +/- 3.3 vs 11.5 +/- 4.8 min; p < 0.05). No differences were recorded on scales reflecting intermediate-term recovery. Analgesic consumption and the incidence of side effects were similar in both groups. CONCLUSIONS: Sevoflurane and propofol are comparable for anesthetic maintenance in urological and neurological procedures of intermediate duration.

Anesthesia↗