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Jean-Yves Scoazec

Publications and source records attributed to Jean-Yves Scoazec.

At least 37 records · Page 2Linked to original sources
PubMed2005

[Editorial].

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France↗
PubMed2005

[Gastrointestinal stromal tumors: definition, histological, immunohistochemical, and molecular features, and diagnostic strategy].

Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Major advances in their definition and classification and the understanding of their molecular mechanisms have recently been made. These advances have resulted in the delineation of a treatment that has become a model of targeted therapy in oncology. GISTs are defined as tumors of the gastrointestinal tract, but also of the mesentery and peritoneum, constituted by a proliferation of usually spindle-shaped, rarely epithelioid cells, usually, but not consistently expressing the KIT protein. Most GISTs are associated with molecular abnormalities in two target genes: KIT (which encodes the KIT protein) and PDGFRA (which encodes the A chain of the PDGF receptor). The diagnosis of GIST relies on histological arguments (proliferation of spindle-shaped cells in 70% of cases, of epithelioid cells in 20%; histological variants are rare and sometimes misleading) and on immunohistochemical arguments (expression of KIT in 95%, usually associated with CD34 expression in 60%-70% of cases). The demonstration of mutations in target genes is required only in cases that are histologically suggestive but KIT-negative; beyond this indication, this is only undertaken in research protocols. The differential diagnosis of GIST includes the other mesenchymal tumors of the gastrointestinal tract, such as leiomyomas and leiomyosarcomas, and the digestive locations of some sarcomas; it relies on both histological and immunohistochemical arguments. The evaluation of the prognosis is essential. According to the current concept, every GIST carries a risk of malignancy, which may vary from very low to very high. Prognosis is based on a simple algorithm using two histoprognostic parameters, i.e., tumor size and mitotic index. The treatment of localized GIST is surgical resection, which must be complete; that of advanced or unresectable GIST is based on the use of a targeted therapy, imatinib, which is a pharmacological antagonist of the KIT protein. Proper understanding and utilisation of the diagnostic criteria and classification of GIST by pathologists are essential for good patient management.

Adult↗
PubMed2005

[Endocrine tumors: biology and physiopathology].

Endocrine tumors are defined as neoplastic lesions resulting from the proliferation of cells engaged in an endocrine differentiation pathway, as shown by their expression of a set of specific markers, including true endocrine markers (such as chromogranine A) and neuro-endocrine markers, shared between neurons and endocrine cells (such as synaptophysin). The demonstration of the synthesis and secretion of one or several hormones is not necessary for the assessment of the endocrine nature of a tumor; only tumors associated with a clinical syndrome resulting from hormone overproduction can be said functioning endocrine tumors. Beyond their common features, endocrine tumors are characterized by a marked diversity, which results from the large functional, structural and embryological heterogeneity of normal endocrine cells. The natural history of endocrine tumors is also characterized by a marked heterogeneity in their evolution and rate of progression. While most endocrine tumors are locally and slowly evolving, some of them behave as truly malignant tumors, as shown by their capacity of metastatic dissemination and their fatal evolution. A better understanding of the cellular and molecular mechanisms involved in tumor progression and metastatic dissemination is necessary for the identification of new prognostic tools and novel therapeutic targets.

Cell Division↗
PubMed2005

[Practical notes for the evaluation of malignancy in digestive endocrine tumors].

For a long time, the assessment of malignancy risk and patient outcome in digestive endocrine tumors had to rely on sparse and mostly unconfirmed data. The 2000 WHO classification with its standardized scheme of pathologic report constitutes a framework facilitating the assessment of tumor malignancy and has been regarded to be useful for clinical purposes, providing the basis for proper patient management and for designing treatment protocols. The classification is based on a combination of pathological and clinical features with parameters specific for each organ in which the endocrine tumors originate. Three main categories are considered: 1) well differentiated endocrine tumors, further subdivided into tumors with benign and with uncertain behavior; 2) well differentiated endocrine carcinomas, low grade; and 3) poorly differentiated endocrine carcinomas, high grade. In this review the differential tumor characteristics between the above categories are summarized. The relevance of additional features as for tumor prognostication, chiefly the Ki67 proliferation index and malignancy associated genetic changes, is discussed with emphasis on the discrepancies emerging between tumors of foregut and midgut origin.

Diagnosis, Differential↗
PubMed2005

[Mixed endocrine tumors].

Mixed endocrine tumors are tumors composed of at least two distinct tumor populations, one of which is endocrine. Because of their rarity and unusual presentation, endocrine mixed tumors raise many problems of diagnosis, management and therapy. Three main types of endocrine mixed tumors are recognized: The existence of these various types has been confirmed by recent molecular studies, even if the same studies have also shown that the histogenesis of a mixed endocrine tumor cannot be predicted from its histological features. Composite tumors are the less rare mixed tumors. The recent WHO classification recommends to restrict the term of composite endocrine tumor to the epithelial tumors containing at least 30% of obviously tumoral endocrine cells; some authors recommend to use higher thresholds, of at least 50%, in order to avoid overdiagnosis. The endocrine component is usually well differentiated, easily identified by its suggestive histological features; the endocrine nature of tumor cells is confirmed by the immunodetection of specific endocrine and neuro-endocrine markers (such as chromogranin A and synaptophysin). In some cases, the endocrine component is poorly differentiated: the demonstration of neuro-endocrine markers is necessary to confirm the diagnosis. Mixed tumors can occur in every anatomical site; they are more frequent in organs containing endocrine cells in the normal state (especially the digestive tract and the pancreas), but they can also be observed in organs devoid of endocrine cells (such as the mammary gland). The management of mixed endocrine tumors must take into account the more aggressive component. Mixed tumors containing a well differentiated endocrine component and an adenocarcinomatous component are to be treated like adenocarcinomas. Mixed tumors containing a poorly differentiated endocrine component must be considered as poorly differentiated endocrine carcinomas.

Colonic Neoplasms↗
PubMed2005

[Eosinophilic esophagitis: 3 case reports].

Eosinophilic esophagitis is a rare entity, characterized by eosinophilic infiltration of the oesophagal mucosae, with no gastroesophageal reflux. Food allergies are often involved. We report 3 paediatric cases of eosinophilic esophagitis, revealed by dysphagia, with or without stricture. Eosinophilic esophagitis is a rare disease, but its frequency is probably underestimated. Symptoms are sometimes unusual. Oesogastroscopy with biopsy is essential for the diagnosis. Food allergies can be involved and must be systematically investigated.

Child↗
PubMed2005

Fatty infiltration of the liver. Detection and grading using dual T1 gradient echo sequences on clinical MR system.

AIM: To evaluate the relationship between histopathology results and magnetic resonance imaging (MRI) on in and opposed-phase sequences grading of fat deposition within human liver. MATERIALS AND METHODS: In and opposed-phase T1-weighted gradient-echo sequences (double echo time 2.3 ms and 4.6 ms) were performed in 25 patients, using a 1.5-T clinical MR imaging system. Fat/water ratio on in- and opposed-phase images of the liver was compared with pathologically defined degree of steatosis. The signal intensity in the images was acquired with operator-defined regions of interest at the same location in both fat and water images and the ratio was calculated by dividing signal intensity of liver in opposed phased sequence on signal intensity of liver in phased sequence. Fat/water ratio and the degree of steatosis were compared using linear regression. The sensitivity and specificity of opposed-phase for diagnosing steatosis were defined by ROC analysis. Furthermore, a correlation between visual signal intensity variation and the degree of steatosis was assessed using Pearson correlation coefficient. RESULTS: Histology demonstrated fatty liver infiltrations in 81% of specimens. The percentage of fatty hepatocytes was 28 +/- 30%. Fat/water ratio was significantly correlated with the pathologic grading of steatosis (r = 0.816, P < 0.001). The opposed phase MR imaging sensibility and specificity for the diagnosis of hepatic steatosis were respectively 80% and 71%. We obtained a statistically significant correlation between visual SIV and fatty liver grading (P = 0.017). CONCLUSION: We demonstrated a significant correlation between fat/water ratio and histological findings for the detection and grading of fatty liver.

Adipose Tissue↗
PubMed2005

Clear cell myomelanocytic tumor (PEComa) of the duodenum in a child with a history of neuroblastoma.

We report herein a case of digestive clear cell myomelanocytic tumor (PEComa) that is unique in its location and presentation. The lesion, located in the duodenal wall, was diagnosed in a child with a history of cervical neuroblastoma that was in remission after surgical resection and chemotherapy. The diagnosis was obtained by examination of a biopsy specimen taken during laparoscopy. The decision was made to perform surgical resection. Examination of the surgical specimen confirmed the diagnosis of PEComa. No metastasis was found. After 2 years of follow-up, the patient is alive, without evidence of metastasis or recurrence. This case highlights the distinctive characteristics of the cells in PEComa, recognizable even on limited biopsy material. It also suggests a possible association between PEComa and neuroblastoma, 2 unusual tumors that belong to the spectrum of lesions known to occur in patients with tuberous sclerosis and that may share a possible common pathogenetic mechanism.

Adenocarcinoma↗
PubMed2005

[Recommendations for the management of GIST patients].

BACKGROUND: The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last years. A national consensus meeting was therefore organized in order to identify the optimal management procedures for patients with GIST in localized and advanced stages. METHODS: A panel of different specialties, including pathology, molecular biology, imaging, surgery, gastroenterology, medical oncology reviewed the current literature, in particular the recent Lugano conference, to identify consensus points and topics for future research in four different working groups: pathology and molecular biology, early management of small tumors and imaging, surgery, and medical treatment. Consensus points were categorized according to the Standard Options Recommendations (SOR) of the French Federation of Cancer Centers. RESULTS: The standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is advisable for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. Resection of metastases is also considered as an experimental procedure which can not be recommended routinely. The criteria for tumor response to imatinib should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield units) on computed tomography, metabolic activity (i.e. reduction of FDG uptake on positron emission tomography), and reduction of vascularisation of the tumors using contrast enhanced ultrasound evaluation. An increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response. CONCLUSIONS: Consensus points in clinical management of GIST in this national conference adopted the majority of consensus points published in the Lugano conference. This multidisciplinary work will be published in the reference oncology, gastroenterology, and pathology journals in French languages.

Antineoplastic Agents↗
PubMed2004

The role of fibroblasts in the modulation of integrin-dependent interactions between the gastric cell line HGT-1 and fibronectin.

Fibronectin plays an important role in gastric cancer progression. However, little is known about the microenvironmental factors modulating integrin-dependent interactions between gastric cancer cells and fibronectin. We therefore studied the regulation by fibroblasts of the integrin-dependent adhesion and migration of the gastric cancer cell line HGT-1 onto fibronectin. We first determined, by immunofluorescence, immunoblotting and flow cytometry, that HGT-1 cells expressed alpha3, alpha5, alpha6, alphaV and beta1 integrin chains, and the alphaVbeta3 and alphaVbeta5 dimers. We verified that HGT-1 cells xenografted to the immunosuppressed newborn rat retained the integrin repertoire detected in vitro and were able to induce the formation of tumors rich in fibronectin. By using an in vitro assay in the presence of neutralizing antibodies, we verified that HGT-1 adhesion and migration onto fibronectin involved beta1, alphaV and alpha5 integrin chains; we verified, by using an in situ adhesion test to rat gastric wall frozen sections, that in situ HGT-1 adhesion to fibronectin was integrin dependent. In coculture experiments, we showed that organ-specific fibroblasts from stomach, lung and dermis were able to induce, in a site-specific manner, the expression of beta1, alpha5 and alphaV integrin chains in HGT-1 cells, their integrin-dependent adhesion and migration on fibronectin and their capacity to secrete oncofetal fibronectin. In conclusion, our results show the capacity for tissue-derived fibroblasts to modulate the integrin-dependent interactions between the gastric cell line HGT-1 and fibronectin. They strongly suggest that, in gastric cancer, stromal fibroblasts contribute to promote fibronectin-mediated local invasion by tumor cells.

Animals↗
PubMed2004

Netrin-1 controls colorectal tumorigenesis by regulating apoptosis.

The expression of the protein DCC (deleted in colorectal cancer) is lost or markedly reduced in numerous cancers and in the majority of colorectal cancers due to loss of heterozygosity in chromosome 18q, and has therefore been proposed to be a tumour suppressor. However, the rarity of mutations found in DCC, the lack of cancer predisposition of DCC mutant mice, and the presence of other tumour suppressor genes in 18q have raised doubts about the function of DCC as a tumour suppressor. Unlike classical tumour suppressors, DCC has been shown to induce apoptosis conditionally: by functioning as a dependence receptor, DCC induces apoptosis unless DCC is engaged by its ligand, netrin-1 (ref. 3). Here we show that inhibition of cell death by enforced expression of netrin-1 in mouse gastrointestinal tract leads to the spontaneous formation of hyperplastic and neoplastic lesions. Moreover, in the adenomatous polyposis coli mutant background associated with adenoma formation, enforced expression of netrin-1 engenders aggressive adenocarcinomatous malignancies. These data demonstrate that netrin-1 can promote intestinal tumour development, probably by regulating cell survival. Thus, a netrin-1 receptor or receptors function as conditional tumour suppressors.

Adenocarcinoma↗