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J Forteza

Publications and source records attributed to J Forteza.

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↗
PubMed2004

Serum levels of tissue polypeptide specific antigen are correlated with hepatocyte cytokeratin expression in alcoholic liver disease.

BACKGROUND: Serum levels of the tumor marker tissue polypeptide specific antigen (TPS, cytokeratin 18 fragments) are increased in patients with alcoholic liver disease, particularly in cases of alcoholic hepatitis. Mallory bodies, characteristic of alcoholic hepatitis, are cytokeratin 8 and 18 aggregates. The study was aimed at investigating the possible relationship of serum TPS levels with hepatocyte cytokeratin expression in patients with alcoholic liver disease. METHODS: Twenty-four patients with alcoholic liver disease were studied. Immunohistochemical staining for cytokeratins 8 and 18 was performed in liver specimens by means of CAM 5.2 monoclonal antibody. The number of hepatocytes containing CAM 5.2-reactive cytokeratin inclusions was compared with serum TPS levels. MAIN RESULTS AND CONCLUSIONS: The vast majority of alcoholics (95%) showed increased (>100 units/liter) serum TPS levels. Serum TPS levels were significantly correlated with the number of hepatocyte cytokeratin inclusions. Serum TPS levels can predict hepatocyte cytokeratin expression in patients with alcoholic liver disease.

Adult↗
PubMed2004

Liver-cell adenomas with heavy iron deposition.

We report 3 unusual cases of liver cell adenomas with some uncommon features, corresponding to 3 women aged 45, 37, and 41 years, respectively. The diagnosis was incidental in 2 cases, and the third presented with abdominal pain. Radiologic findings were consistent with liver-cell adenoma, but gross examination failed to reveal the lesion until 24 hours of formalin fixation in 2 cases. Histopathological examination showed a striking deposition of iron pigment. In fact, Pearl's stain was the best way to visualize the limits of the neoplasm, which were irregular (pseudo-infiltrative). There was no evidence of other architectural or cytologic features suggesting an alternative diagnosis, particularly liver-cell carcinoma. Follow-up ranged from 9 months to 6 years and all patients are free of disease.

Adenoma, Liver Cell↗
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↗
PubMed2003

MOC-31/Ep-CAM immunoreactivity in Merkel cells and Merkel cell carcinomas.

AIMS: To evaluate the monoclonal antibody MOC-31 in Merkel cell carcinomas and normal Merkel cells. Merkel cell carcinoma is a rare and aggressive tumour that occurs mainly in elderly individuals. The histological diagnosis of Merkel cell carcinoma can be difficult because it looks similar to other small blue cell tumours, particularly skin metastases of small-cell lung carcinomas. This antibody recognizes the epithelial cell adhesion molecule (Ep-CAM), that has been assigned to the small cell lung cancer cluster 2 of antibodies. To the best of our knowledge, immunostaining for MOC-31/Ep-CAM has not been previously described in Merkel cells or Merkel cell carcinomas. METHODS AND RESULTS: Thirty-one cases of Merkel cell carcinoma and three samples of normal human fingertip were selected to analyse the expression of MOC-31/Ep-CAM by immunohistochemistry. A high number of Merkel cell carcinomas (21/31, 67.7%) showed intense and readily interpretable positivity. Immunostaining was diffuse or focal and always localized to the plasma membrane. Normal Merkel cells of human fingertip also showed plasma membrane immunoreactivity for MOC-31/Ep-CAM. CONCLUSION: The demonstration of positivity for MOC-31/Ep-CAM in Merkel cell carcinomas precludes the use of this immunohistochemical marker to distinguish between tumours and skin metastases of small-cell lung carcinoma.

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↗
PubMed2001

Analysis of 2 antiapoptotic factors in gliomas: bcl-2 overexpression and p53 mutations.

BACKGROUND: p53 mutations and immunoreactivity have been described in human gliomas. During the past few years, some authors have found bcl-2 overexpression in astrocytomas, although their correlation with histological grade is a matter of disagreement. A relation between bcl-2 overexpression and p53 immunoreactivity has also been suggested. OBJECTIVES: To analyze the frequency of presentation of bcl-2 and p53, their clinicopathologic implications, and their possible coexpression. METHODS: We studied p53 and bcl-2 with immunohistochemical and molecular methods in 61 gliomas (including 21 astrocytomas, 9 anaplastic astrocytomas, 29 glioblastomas, 1 oligodendroglioma, and 1 mixed glioma). RESULTS: We discovered a high level of bcl-2 overexpression (57%). Overexpression of bcl-2 can be an early event in gliomas tumorigenesis, although no correlation was found with any of the clinicopathologic parameters studied. p53 mutations were present in a small proportion of gliomas (17%). p53 immunoreactivity was present in 34 cases (57%), and it was related to histological grade and a supratentorial location. A high percentage of tumors (26 cases, 42%) presented p53 immunoreactivity without p53 mutations. CONCLUSIONS: Since there was no relation between bcl-2 overexpression and p53 mutations or p53 immunoreactivity, both factors may not act together in the genesis and evolution of gliomas.

Adolescent↗
PubMed2000

Goodpasture antigen-binding protein, the kinase that phosphorylates the goodpasture antigen, is an alternatively spliced variant implicated in autoimmune pathogenesis.

The non-collagenous C-terminal domain of the alpha(3) chain of collagen IV is the autoantigen in Goodpasture disease, an autoimmune disorder described only in humans. Specific N-terminal phosphorylation is a biological feature unique to the human domain when compared with other homologous domains lacking immunopathogenic potential. We have recently cloned from a HeLa-derived cDNA library a novel serine/threonine kinase (Goodpasture antigen-binding protein (GPBP)) that phosphorylates the N-terminal region of the human domain (Raya, A. Revert, F, Navarro, S. and Saus J. (1999) J. Biol. Chem. 274, 12642-12649). We show here that the pre-mRNA of GPBP is alternatively spliced in human tissues and that the most common transcript found encodes GPBPDelta26, a molecular isoform devoid of a 26-residue serine-rich motif. Recombinantly expressed GPBPDelta26 exhibits lower activity than GPBP, due at least in part to a reduced ability of GPBPDelta26 to interact and to form very active high molecular weight aggregates. In human tissues, GPBP shows a more limited expression than GPBPDelta26 but displays a remarkable preference for the small vessels and for histological structures targeted by natural autoimmune responses including alveolar and glomerular basement membranes, the two main targets in Goodpasture disease. GPBP expression is, in turn, up-regulated in the striated muscle of a Goodpasture patient and in other autoimmune conditions including cutaneous lupus erythematosus, pemphigoid, and lichen planus.

Alternative Splicing↗