Biomedical subjects

Máximo Fraga

Publications and source records attributed to Máximo Fraga.

6 recordsLinked to original sources

PubMed2004

Mesenchymal hamartoma of the liver; Clinicopathological, immunohistochemical and flow cytometric study of two cases.

Mesenchymal hamartoma (MH) is a rare liver lesion of infancy. Due to its rapid increase in size, it is often misdiagnosed clinically as a malignant tumour or as a hepatic cyst because of its cystic appearance. We present the clinicopathological, immunohistochemical and flow cytometric features of two cases, involving an 11-month-old boy and a 13-month-old girl. In both cases, the histological appearance and the immunohistochemical findings were identical. Bile ducts and blood vessels showed the expected immunohistochemical profile, whereas the mesenchymal component showed immunoreactivity not only for vimentin but also for muscular markers. Flow cytometry disclosed an aneuploid population in one case, thus favouring the interpretation of MH as a neoplastic lesion. Unlike the characteristically continuous and rapid growth of MH before or shortly after birth, these two cases showed low proliferative and apoptotic indexes and a high immunohistochemical expression of bcl-2 protein. This prompted us to hypothesize that MH might undergo a brief initial proliferative phase, but the cells would later become 'immortalized' by bcl-2 overexpression.

Journal Article↗

PubMed2004

Building an outcome predictor model for diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) patients are treated using relatively homogeneous protocols, irrespective of their biological and clinical variability. Here we have developed a protein-expression-based outcome predictor for DLBCL. Using tissue microarrays (TMAs), we have analyzed the expression of 52 selected molecules in a series of 152 DLBCLs. The study yielded relevant information concerning key biological aspects of this tumor, such as cell-cycle control and apoptosis. A biological predictor was built with a training group of 103 patients, and was validated with a blind set of 49 patients. The predictive model with 8 markers can identify the probability of failure for a given patient with 78% accuracy. After stratifying patients according to the predicted response under the logistic model, 92.3% patients below the 25 percentile were accurately predicted by this biological score as "failure-free" while 96.2% of those above the 75 percentile were correctly predicted as belonging to the "fatal or refractory disease" group. Combining this biological score and the International Prognostic Index (IPI) improves the capacity for predicting failure and survival. This predictor was then validated in the independent group. The protein-expression-based score complements the information obtained from the use of the IPI, allowing patients to be assigned to different risk categories.

Adolescent↗

PubMed2002

Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays.

Tumoral cells in Hodgkin lymphoma (HL) display an increased growth fraction and diminished apoptosis, implying a profound disturbance of the cell cycle and apoptosis regulation. However, limitations of molecular techniques have prevented the analysis of the tumor suppressor pathways and cell-cycle checkpoints. Tissue microarray (TMA) is a powerful tool for analyzing a large number of molecular variables in a large series of tumors, although the feasibility of this technique has not yet been demonstrated in heterogeneous tumors. The expression of 29 genes regulating the cell cycle and apoptosis were analyzed by immunohistochemistry and in situ hybridization in 288 HL biopsies using TMA. The sensitivity of the technique was validated by comparing the results with those obtained in standard tissue sections. The results revealed multiple alterations in different pathways and checkpoints, including G1/S and G2/M transition and apoptosis. Striking findings were the overexpression of cyclin E, CDK2, CDK6, STAT3, Hdm2, Bcl2, Bcl-X(L), survivin, and NF-kappaB proteins. A multiparametric analysis identified proteins associated with increased growth fraction (Hdm2, p53, p21, Rb, cyclins A, B1, D3, and E, CDK2, CDK6, SKP2, Bcl-X(L), survivin, STAT1, and STAT3), and proteins associated with apoptosis (NF-kappaB, STAT1, and RB). The analysis also demonstrated that Epstein-Barr virus (EBV)-positive cases displayed a characteristic profile, confirming the pathogenic role of EBV in HL. Survival probability depends on multiple biologic factors, including overexpression of Bcl2, p53, Bax, Bcl-X(L), MIB1, and apoptotic index. In conclusion, Hodgkin and Reed-Sternberg cells harbor concurrent and overlapping alterations in the major tumor suppressor pathways and cell-cycle checkpoints. This appears to determine the viability of the tumoral cells and the clinical outcome.

Apoptosis↗

PubMed2002

Cellular localization of orexin receptors in human adrenal gland, adrenocortical adenomas and pheochromocytomas.

Orexin-A and -B are hypothalamic peptides derived from a precursor called prepro-orexin and related with the regulation of the energy balance and arousal. They act on G protein receptors named orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). In the present study, we used immunohistochemical techniques to detect the distribution of OXR in normal human adrenal gland and adrenal tumours (adrenocortical adenomas and pheochromocytomas). OX1R was expressed in the cortex of the normal human adrenal gland (glomerulosa, fasciculata and reticular zones) and OX2R was located in the medulla (epinephrine and norepinephrine cells). By the double immunofluorescence techniques, we demonstrated that virtually all medullar cells (epinephrine and norepinephrine cells) expressed OX2R. As was expected, according to the results obtained in normal tissues, cortical tumours (adrenocortical adenomas) were positive for OX1R but not for OX2R and conversely, medullar tumours (pheochromocytomas) expressed only OX2R.

Adolescent↗

PubMed2002

Predictors of malignant behaviour in gastrointestinal stromal tumours: a clinicopathological study of 34 cases.

OBJECTIVE: The clinicopathological features of gastrointestinal (GI) stromal tumours were analysed to find out the features that influence prognosis in these neoplasms. DESIGN: Retrospective study. SETTING: University Hospital, Spain. SUBJECTS: Review of clinical records and analysis of a series of GI stromal tumours classified in three groups: benign = 7 leiomyomas, malignant or potentially malignant = 16 combined smooth muscle-neural tumours, and 2 miscellaneous, and definitely malignant = 1 leiomyosarcoma and 8 gastrointestinal autonomic nerve tumours. MAIN OUTCOME MEASURES: Electron microscopy and immunohistochemical staining for vimentin, smooth muscle actin, muscle specific actin, desmin, S-100 protein, neuronal specific enolase, chromogranin A, synaptophysin, CD34, CD117 (c-kit), Bcl-2, and Ki-67. RESULTS: We found significant differences (p < 0.0001) between the median (P25, P75) size of tumours in the benign group 2.0 (1.2, 3.5) and in the potentially 7.5 (4.0, 13.0) and definitely 5.0 (4.0,6.5) malignant groups. The percentage of mitoses was lower (p = 0.003) in the benign group 0.4 (0.5) than in the other groups 2.0 (1.0, 5.0). Immunoreactivity for CD117 in leiomyomas was an unexpected finding; this showed a different staining pattern from the diffuse and homogeneous staining in GI stromal tumours. In addition, the MIB-1 proliferation index differentiated (p = 0.002) between the benign group 1.5 (1.0, 2.5) and the other two groups 7.0 (3.0, 11.0). CONCLUSIONS: These findings support the idea that GI stromal tumours form a heterogeneous group of neoplasms in which large size, presence of necrosis, and a high proliferative index (mitotic rate or MIB-1 index, or both) are good predictors of malignant behaviour.

Adult↗

PubMed2002

Sclerosing epithelioid fibrosarcoma primary of the bone.

Sclerosing epithelioid fibrosarcoma (SEF) is an uncommon tumor originally described in soft tissues. We report a case of SEF primary of the left iliac bone in a 42-year-old woman. The tumor was grossly well circumscribed. The histologic examination disclosed a hypocellular neoplasm with densely hyalinized stroma. It was composed predominantly of small-to-moderate-sized round-to-ovoid cells, relatively uniform, often with clear cytoplasm, and arranged in nest, cord, and strand patterns. Because the distinctive morphologic patterns and the immunohistochemical profile of this entity may be mistaken for many different tumors, we here emphasize the differential diagnostic problems of this variant of fibrosarcoma. To our knowledge, this is the first tumor of this kind described in the bone.

Adult↗