[Juxtacortical chondrosarcoma. A entity to be differentiated from periosteal osteosarcoma].
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Adolescent↗
Biomedical subjects
J Hassoun
Publications and source records attributed to J Hassoun.
[Clear cell sarcoma of the kidney relapsing after 10 years of asymptomatic evolution].
We report the case of a kidney tumor occurring in a thirteen year-old girl. This tumor was first diagnosed and treated as a benign one. After ten years without recurrence, a relapse occurred. The diagnosis was recurrent clear cell sarcoma of the kidney. The course in our case is uncommon because clear cell sarcoma of the kidney is a rare and aggressive pediatric neoplasm, usually characterized by a predilection for bone metastases, and a mid survival rate of 30 months without treatment.
Adolescent↗
[An exceptional variety of medulloblastoma: melanotic medulloblastoma].
We report a new case of melanotic medulloblastoma of the vermis in a 3 1/2 year old boy. This tumor showed a typical histological appearance with pseudoepithelial pigmented structures immunoreactive for S100 protein and vimentin. The tumor did not recur after total surgical removal and post operative radiation. However, after a 10 year follow-up, imaging demonstrated that a second tumor occurred in the left cerebellar hemisphere, which, on histological examination, was a typical glioblastoma. Hypothesis concerning the histogenesis of the second tumor, as well as a causal association with radiation therapy and possible contribution of growth hormone therapy are discussed.
Cerebellar Neoplasms↗
Molecular analysis of the NPM-ALK rearrangement in Hodgkin's disease.
The fusion gene NPM-ALK occurs in a subset of anaplastic large cell lymphomas (ALCLs), as a result of a chromosomal translocation, t(2;5) (p23;q35). It has been suggested that Hodgkin's disease (HD) and ALCL share a common histogenesis because of pathological and phenotypical similarities. In order to check this hypothesis, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to detect the hybrid NPM-ALK gene in 30 tumour samples, including 22 lymph node biopsies from HD and eight ALCL specimens. The threshold level of sensitivity was shown to reach at least 1/10(4) by dilution experiments using cell lines as positive and negative controls. The expected 177 bp product indicative of the NPM-ALK rearrangement was identified in Karpas 299 and SUDHL-1 cell lines and in two out of eight ALCLs. The 22 HD cases were negative, even after two successive tests. Thus, since the ALCL-specific genetic alteration was absent in our series of HD cases, the present study does not support the hypothesis that HD and ALCL are histogenetically related entities.
Adult↗
Predominant expression of the long isoform of Bcl-x (Bcl-xL) in human lymphomas.
Bcl-x is a member of the bcl-2 family of proteins which are characterized by their ability to modulate apoptosis. Alternative splicing results in two distinct bcl-x mRNAs encoding a long isoform, bcl-xL, which acts as a bcl-2 agonist; and a short isoform, bcl-xS, which inhibits bcl-2 effects. The aim of the study was to determine whether bcl-x is expressed in lymphoma tissues and to characterize the respective production of bcl-xs and bcl-xL. We investigated the expression of bcl-x mRNA in a series of 50 non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD) cases using a RT-PCR method in order to amplify both transcripts simultaneously, and to estimate their relative abundance. The rearrangements of the bcl-2 gene were analysed by RT-PCR expression of the hybrid bcl-2-lgH mRNA. In addition, 20 PCR-positive NHL cases and three HD cases were analysed by immunohistochemistry using bcl-x polyclonal antisera. RT-PCR showed bcl-x expression in 43/45 NHLs and 5/5 HD cases. The bcl-xL transcript was predominant in all positive cases and was associated with variable amounts of bcl-xS. There was no significant correlation between the profile of bcl-xL/bcl-xS expression and the histological and immunological subtyping. Bcl-x immunodetection was positive in the neoplastic cell component in all analysed cases, but the degree of staining was highly variable between cases. Expression of the hybrid bcl-2-IgH gene was detected by RT-PCR in five cases of follicular NHL and in one case of HD, but this group of tumours did not display a particular profile of bcl-xL/bcl-xS expression. We conclude that bcl-x is commonly expressed by malignant cells in various types of malignant lymphomas, with a predominance of the bcl-xL transcript. Since the corresponding bcl-xL isoform can block the cell death machinery and potentialize bcl-2 effects, it may be involved in some pathways of lymphomagenesis.
Base Sequence↗
Expression of FGF1 and FGFR1 in human melanoma tissues.
Fibroblast growth factor 2 (FGF2) has been implicated in the pathogenesis of malignant melanoma (MM), but the role of other FGFs and their receptors (FGFRs) is not elucidated. To determine whether FGF1 and FGFR1 may be involved in MM growth in vivo, we have studied the expression of the FGF1 and FGFR1 genes in 77 fresh MM biopsy samples, using RT-PCR analysis. Samples of benign nevi, normal skin and carcinoma cell lines were included as controls. Using RT-PCR analysis, expression of FGF1 and FGFR1 was observed in 69/77 and 68/77 cases, respectively. Immunohistochemical detection of the FGFR1 protein was positive in reactive stromal cells and at a much lower level in neoplastic cells. In situ hybridization experiments demonstrated FGFR1 mRNA mainly located in the stromal component. Southern blot analysis of genomic DNA prepared from MM tumors did not show any structural alteration of the FGFR1 gene. There was no correlation between FGF1/FGFR1 expression and the usual clinicopathological parameters of MM. We conclude that FGF1 and FGFR1 are frequently co-expressed in MM, a situation that may contribute to aberrant autocrine and paracrine pathways. Due to the absence of correlation with clinico-pathological parameters, this expression cannot be used as a marker of prognosis in the management of MM patients.
Actins↗
Gastrointestinal hormone mRNA expression in human colonic adenocarcinomas, hepatic metastases and cell lines.
Aims-(1) To investigate the expression of the four main hormones of the digestive tract by performing reverse transcription polymerase chain reaction (RT-PCR) on a series of samples, comprising tumoral and healthy colonic tissues, hepatic metastases and colonic cell line samples; and (2) to study the patterns of labelling obtained with serological and morphological markers.Methods-After extraction and reverse transcription, gastrin, somatostatin, cholecystokinin (CCK) and transforming growth factor alpha (TGFalpha) mRNAs were detected by PCR and nested PCR using specific primers. The corresponding proteins were detected by immunohistochemistry.Results-The cell lines expressed all four mRNAs. Gastrin mRNA was present in most tumoral and metastatic samples, while the somatostatin transcript was detected in all samples and was frequently overexpressed in the normal colon. TGFalpha mRNA was expressed systematically in tumours of the right and transverse colon, but not in those located in the left colon; the expression of CCK mRNA was systematically absent in the left colon.Conclusions-The data presented here shed some light on the transcriptional events involved in the production of the various hormones present in the gastrointestinal tract, in both healthy and tumoral tissues. The various mRNAs expressed in cell lines are therefore not systematically expressed in the human pathology.
Journal Article↗
[Pancreatic and duodenal somatostatinoma. Two clinico-pathologic entities].
Somatostatinomas are endocrine tumors with predominant secretion of somatostatin. The majority occur in the pancreas and the duodenum. However, distinctive clinico-pathologic features are reported for both of them. The features of pancreatic somatostatinomas are a larger size, a more frequent clinical expression, a female predominance and a poorer prognosis. Duodenal somatostatinomas are characterized by psammoma bodies at histologic examination. We report here two cases of pancreatic and ampullary somatostatinomas, focusing on the main diagnostic problems and on the characteristics of each tumoral localization.
Aged↗
PCR-mismatch analysis of p53 gene mutation in Hodgkin's disease.
Expression of the p53 protein can be detected by immunohistochemistry in Reed-Sternberg (RS) cells, the presumed neoplastic component of Hodgkin's disease (HD) lesions. At present, there is no clear molecular evidence that p53 positive immunostaining in HD correlates with the presence of mutations or other structural alterations of the p53 gene. To address this question, 49 cases of HD have been investigated for p53 expression by immunohistochemistry, using the DO1 monoclonal antibody on paraffin sections. Thirty-seven out of 49 cases (75 per cent) exhibited positive immunostaining restricted to RS cells and variants. Among these 37 positive cases, ten cases were selected on the basis of a rich content of RS cells showing virtually 100 per cent DO1 positivity. A PCR-mismatch strategy was chosen for the detection of p53 mutations. The threshold level of sensitivity was assessed on positive cell-line controls. A proportion of 10-15 per cent p53 mutated cells mixed in a normal population could be identified. Total genomic DNA was extracted from the ten selected HD cases and PCR amplification of exons 5-8 of the p53 gene was performed. Heteroduplex mismatch analysis revealed no structural alterations of the p53 gene in any case. In view of these findings, it appears unlikely that the sensitivity of the method by itself can fully explain the negative results, although this possibility cannot be completely ruled out. Thus, it is conceivable that p53 positive immunostaining in HD may not necessarily imply genomic alterations in the classic 'hot spot' regions and may be related to another mechanism of p53 protein stabilization.
Gene Expression↗
Mixed desmoplastic primitive neuroepithelial tumor of infancy: a light microscopic, immunocytochemical, ultrastructural and genetic study.
We describe a case of a desmoplastic brain tumor which was initially resected from the right fronto-temporal region in a 2 year-old boy. This nodular, calcified tumor was vascularized by the internal carotid artery and the middle meningeal artery branches. Grossly, it contained several mucoid cysts. Light microscopy showed cords or nests of small cuboidal cells surrounded by a loose connective tissue and desmoplastic areas containing fibers and spindle cells. The cuboidal cells expressed epithelial, neuronal and neuroendocrine markers. Some foci of spindle cells showed glial differentiation. The tumor recurred 16 months later and displayed some characteristics of the small cell neuroepithelial component, mitoses being conspicuous. Electron microscopy revealed undifferentiated clear cells, some containing neurosecretory granules. Karyotyping demonstrated the following formula: < 15 > 46, t(8;11) (q13; q11). The chromosome 11 breakpoint was different from that described in Ewing's sarcoma. This isolated translocation has not been previously reported to our knowledge. These unusual features lead us to report this case and to discuss its pathogenesis.
Antibodies↗
Frequent expression of FAS/APO-1 in Hodgkin's disease and anaplastic large cell lymphomas.
FAS/APO-1 (CD95) is a membrane glycoprotein belonging to the tumour necrosis factor/nerve growth factor receptor family, and which can trigger apoptosis in some lymphoid cell lines. Immunohistochemistry combined with Northern blotting allowed determination of the pattern of FAS/APO-1 expression in a series of Ki-1 [CD30] positive lymphoid malignancies, including 27 Hodgkin's disease and eight anaplastic large cell lymphomas. CD30 negative tumours used as controls included 27 B-cell non-Hodgkin's lymphomas. 14 T-cell non-Hodgkin's lymphomas, four reactive lymphadenitis, and non-lymphoid tissues. Immunohistochemistry, performed on frozen sections, revealed a strong FAS/APO-1 expression in 25 out of 27 (92%) Hodgkin's disease cases, predominantly in Reed Sternberg cells; 50 to 100% of the neoplastic cells in eight out of (100%) anaplastic large cell lymphoma cases were positive. In contrast, positive FAS/APO-1 immunostaining was observed only in 22 out of 41 (53%) CD30 negative non-Hodgkin's lymphomas. Northern blot analysis detected variable amounts of the FAS/APO-1 transcript in the immunohistochemistry-positive samples. These results suggest possible hyper-expression of FAS/APO-1 (CD95) in Hodgkin's disease and anaplastic large cell lymphomas.
Gene Expression Regulation, Neoplastic↗
Polymerase chain reaction detection of circulating melanocytes as a prognostic marker in patients with melanoma.
BACKGROUND AND DESIGN: Polymerase chain reaction (PCR) detection of circulating tumor cells from malignant melanoma (MM) was recently described, but the prognostic value of this method in the treatment of patients with MM remained unclear. In the present prospective study, blood samples (n = 193) were collected from 93 patients with MM: 10 stage I patients after primary tumor resection, 18 patients with regional lymph node metastases before node resection, 33 disease-free but high-risk patients (previously treated for node metastases), and 32 patients with distant metastases. Circulating melanocytes were detected using a reverse transcriptase PCR method that analyzes tyrosinase gene expression. All patients were kept under regular surveillance. RESULTS: The PCR assay was always negative in normal individuals and in subjects with non-MM metastatic cancer, while it was positive in 16 of 32 patients with disseminated MM. Five of eight patients who were PCR-positive before node dissection vs one of 10 who were PCR-negative relapsed within 6 months after surgery. In high-risk but apparently disease-free patients, the risk of relapse within the next 6 months was 3.8 times higher after a positive test result. In patients with distant metastases, a positive PCR predicted rapid disease progression. CONCLUSIONS: These data suggest that PCR detection of circulating melanocytes can be considered as a marker for rapid postoperative relapse after node dissection in patients with MM with regional node metastases, for short-term relapse in high-risk disease-free patients, and for rapid and severe progression in patients with distant metastases. This test may have a crucial interest in the treatment of patients with MM.
Base Sequence↗
Optimization of immunohistochemical detection of ERBB2 in human breast cancer: impact of fixation.
In an attempt to standardize the immunohistochemical detection of ERBB2, we evaluated six normal breast samples and 58 breast carcinomas for (1) the effect of four different fixatives (Bouin's fluid, buffered formalin, alcoholic formalin, and methacarn), and (2) the sensitivity and specificity of eight commercially available antibodies. ERBB2 gene copy numbers and RNA transcripts were measured by Southern and Northern blot analysis in all samples. The BT-474 and MCF7 cell lines were processed in the same way as the tissue samples and used a s references of activation or the normal state of the ERBB2 gene, respectively. Complete concordance between immunohistochemistry and molecular biology was observed in 43/58 cases (74 per cent). However, fixation and processing protocols significantly affected the reactivity of the antigenic determinants. The most consistent results were obtained with NCLCB11 on frozen sections and with Tab250 on paraffin-embedded sections. For prospective studies, the use of alcoholic formalin in association with a highly specific antibody (Tab250, 9G6, NCLCB11, or OA-11-854) gave the best results. Methacarn appears to be a reliable fixative, but was studied in only 28 cases. For retrospective studies, the most important parameter to take into account is the sensitivity of the antibody. Thus, with Bouin's fixation, 3B5 was the only reliable antibody, whereas with buffered formalin, Tab250 gave the most consistent results. This study will help inter-laboratory comparisons, and in determining the prognostic significance of ERBB2 expression in breast carcinomas using a standardized methodology.
Antibodies, Monoclonal↗
Expression of the p53 gene in Hodgkin's disease: dissociation between immunohistochemistry and clinicopathological data.
Expression of the p53 protein has been detected recently by immunohistochemistry in Hodgkin's disease (HD), but the relationship between p53 expression and the prognosis and clinicopathological heterogeneity of HD is still unclear. To address these questions we investigated 49 cases of HD for p53 expression by immunohistochemistry using the DO1 monoclonal antibody (MAb) on paraffin sections. Thirty-five cases were simultaneously tested with the 1801 MAb on frozen sections. Thirty-seven of 49 cases (75%) were DO1 positive while 14 of 35 (40%) were PAb 1801 positive. Both MAbs gave a nuclear staining restricted to Reed Sternberg cells (RSCs) and variants and distributed among the three HD subtypes analyzed (ie, nodular lymphocyte predominant, nodular sclerosing, and mixed cellularity). The percentage of positive neoplastic cells in each case was heterogeneous, ranging from almost 100% to less than 5%. In 39 patients for whom clinical data were available statistical analysis did not show any significant correlation between p53-positive immunostaining and clinical staging, B symptoms, probability of relapse, or disease-free survival. We conclude that p53 expression is a common event in HD regardless of histological subtyping, but does not bear any pejorative significance.
Antibodies, Monoclonal↗
NM23 expression in metastasis of malignant melanoma is a predictive prognostic parameter correlated with survival.
The management of patients presenting with metastatic malignant melanoma (MM) is hampered by the substantial variability in survival of these patients and the lack of prognostic markers. In the search for a reliable predictive parameter, we have investigated the expression of the nm23 gene, considered to be a major regulator of the metastatic process. We have analysed by Northern blot the nm23 mRNA level in tumour tissue obtained from metastases of 20 stage II and ten stage III patients with MM. Normal human tissues and benign naevi were simultaneously examined. The level of nm23 expression was highly heterogeneous in MM metastases, with a mean value which was higher than the mean level in normal tissues and naevi. Correlative study was focused on the overall survival following resection of the metastasis in which nm23 Northern blot analysis was performed. Patients displaying higher nm23 expression in metastatic tissue (above the mean level) tended to have a longer survival than others (P = 0.08), and this difference was significant for patients presenting with isolated regional lymph node involvement (P = 0.035). The time from biopsy of the primary MM to the appearance of the first lymph node metastasis also showed a positive correlation with the nm23 mRNA level in this metastasis. The present study is not only in accordance with previous reports showing that the nm23 gene may be implicated in MM progression, but also suggests the reliable value of nm23 expression as a prognostic marker for patients presenting with metastatic MM.
Female↗
Heterogeneity of rearranged T-cell receptor V-alpha and V-beta transcripts in tumor-infiltrating lymphocytes from Hodgkin's disease and non-Hodgkin's lymphoma.
Hodgkin's disease is histologically characterized by the presence of Reed-Sternberg cells (RSC) and reactive cells, including numerous T lymphocytes. Some forms of B cell-non-Hodgkin's lymphoma also contain a rich T-cell population. Previous studies have suggested that the T-cell receptor repertoire of tumor-infiltrating T lymphocytes (TITL) that act specifically against tumor-related antigens, should be restricted. The authors in this study used the polymerase chain reaction to explore the possible existence of such an immunologic response of TITL against RSC or neoplastic B cells. They studied variable (v) region genes of T-cell receptor alpha and beta chains expressed by infiltrating lymphocytes in biopsy specimens from seven patients with Hodgkin's disease and three with B cell-non-Hodgkin's lymphoma. These latter samples were selected based on a rich T-cell content. Primers specific for 18 different V-alpha and 21 V-beta families were used. In every case, TITL showed an unrestricted pattern of expression similar to the repertoire observed in peripheral blood lymphocytes. Although such experiments are limited, the apparent lack of selection of a single or a limited number of T-cell subsets in the affected tissues did not support the existence of an in vivo immunologic interaction between TITL and antigens related to RSC or neoplastic B cells.
Blotting, Southern↗
Detection of gastrin mRNA in paraffin-embedded samples of normal antral mucosae using polymerase chain reaction technique.
Gastrin, a peptide hormone produced by the G cells of the gastric antrum, plays a major role in the regulation of digestive mucosal growth. Although some light has been shed on the peptidic aspects of this hormone's mode of action and the co-regulatory activity in which it is involved along with the other gastrointestinal hormones, little is known at present about the modes of expression of its mRNA at the tissue level. A few attempts have been made so far to detect the transcript, mostly using molecular hybridization techniques. Here it was proposed to detect gastrin mRNA using a RT-PCR technique on a series of paraffin-embedded samples of normal human antrum processed with various fixatives commonly used in histology. The transcript was detectable in all the 7-microns sections of the samples treated with either formalin or Carnoy's solution, whereas Bouin's solution, which is also used as a fixative in histology, was found to have inhibitory effects on the method described here.
Acetates↗
[New WHO classification of central nervous system tumors].
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Brain Neoplasms↗