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J M Coindre

Publications and source records attributed to J M Coindre.

At least 19 recordsLinked to original sources
PubMed2005

[Soft tissue sarcomas: current data in the field of pathology].

Over the last fifteen years, pathology underwent significant changes in the field of soft tissue tumours. They were related to considerable advances in molecular biology and genetics. New data led to the revision of the WHO classification. Malignant fibrous histiocytoma is no longer considered as an entity. It has split up into several subgroups belonging to liposarcomas, leiomyosarcomas or undifferentiated sarcomas. Haemangiopericytoma underwent reappraisal and was put in the same category as solitary fibrous tumour. Many tools have improved. Immunohistochemistry performed with new antibodies had its specificity increased, and became appropriate for the prediction of therapeutic response in some cases, e.g. CD117 detecting mutations of the c-kit proto-oncogen in gastro-intestinal stromal tumours. Refinement of the techniques allows accurate diagnoses from core needle biopsies. Surgical specimens are collegially examined by surgeons and pathologists with special attention paid to resection margins. Although bound by some limitations, the grading system of the French Federation of Cancer Centers has currently remained the best predictor of metastasis-free survival and overall survival of patients. It is based on an assessment of three parameters: differentiation, amount of necrosis, and mitotic count of tumours. The pathologist sets up a diagnosis, and actively takes part in the prediction of the prognosis and therapeutic response. He is one of the major participants in decision making for multimodal treatment of sarcomas.

Humans↗
PubMed2004

Evaluation of MDM2 and CDK4 amplification by real-time PCR on paraffin wax-embedded material: a potential tool for the diagnosis of atypical lipomatous tumours/well-differentiated liposarcomas.

Atypical lipomatous tumours/well-differentiated liposarcomas and dedifferentiated liposarcomas are characterized by 12q13-15 region amplification. In contrast, this molecular event has not been reported in benign lipomas. Within the 12q13-15 chromosomal region, the MDM2, SAS, HMGA2, and CDK4 genes are the most frequent targets of amplification. A series of lipomas (36 cases) and liposarcomas (48 cases) was analysed for MDM2 and CDK4 gene amplification by real-time PCR. MDM2 and CDK4 gene amplification was detected in 2.8% and 5.6% of lipomas and 98.2% and 82.4% of liposarcomas, respectively. Moreover, co-amplification of the two genes as well as a higher-level amplification was observed more frequently in dedifferentiated liposarcomas than in atypical lipomatous tumours/well-differentiated liposarcomas. Real-time PCR proved to be a fast and reliable method to characterize lipomas and liposarcomas by quantification of MDM2 and CDK4 gene amplification. It is applicable to paraffin wax-embedded tissues and could be useful when histological diagnosis is difficult.

Abdominal Neoplasms↗
PubMed2003

DNA topoisomerase IIalpha expression and the response toprimary chemotherapy in breast cancer.

The alpha isoform of Topoisomerase IIalpha (Topo IIalpha) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines. In vitro studies have demonstrated the relationship between the Topo IIalpha expression level and chemosensitivity of target cancer cells. To verify this effect in vivo, we selected 125 patients presenting with T(2)>3 cm and T(3) N(0-1) M(0) breast tumours who were treated by six cycles of primary chemotherapy, including epirubicin before any surgery. Therapy response was assessed by clinical and X-ray mammogram measurements of tumour shrinkage. The pretherapeutic core biopsies were immunostained with a monoclonal antibody (Ki-S7) against Topo IIalpha. Ki-S7 positivity ranged from 0 to 50% (median, 15%). A high percentage of Ki-S7-positive cells (>15%) was associated with tumour regression under chemotherapy (OR=2.88, CI: 1.3-6.4, P=0.004). Ki-S7 further emerged as an independent predictor of tumour regression (OR=3.34, CI: 1.41-7.93, P=0.006), together with tumour size of less than 40 mm (OR=3.82, CI: 1.58-9.25, P=0.002) and negative oestrogen receptor (ER) status (OR=3.35, CI: 1.43-7.86, P=0.005), in a multivariate analysis including tumour size, SBR grade, ER and PR status, Ki-67, p53 and Her-2/neu. Our clinical results confirm in vitro data on the relationship between Topo IIalpha expression and tumour chemosensitivity and thus may have important practical implications.

Adult↗
PubMed2003

Immunohistochemistry in the diagnosis of soft tissue tumours.

Immunohistochemistry is particularly important in the field of soft tissue tumours because of their variety and the frequent difficulty of diagnosis. The first part of this paper discusses useful or new antibodies, together with others that are no longer of use. The second part is devoted to the role of immunohistochemistry in the diagnosis of soft tissue tumours: identification of some rare or atypical benign lesions, identification of non-mesenchymal malignant tumours, and classification of sarcomas. The respective roles of immunohistochemistry and molecular biology are underlined.

Antibodies↗
PubMed2003

[2001 Standards, Options and Recommendations: practice guidelines for difficult diagnoses in surgical pathology or cytopathology in cancer patients].

CONTEXT: The Standards, Options and Recommendations (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVES: To elaborate practice guidelines for difficult diagnoses in surgical pathology or cytopathology in cancer patients. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers. RESULTS: The main recommendations to prevent and reduce the number of difficult diagnoses in surgical pathology or cytopathology are: The main recommendations to detect lesions associated with difficult diagnosis in surgical pathology or cytopathology are: The main recommendations to solve difficult diagnosis in surgical pathology or cytopathology are:

Diagnosis, Differential↗
PubMed2001

Prognostic factors in retroperitoneal sarcoma: a multivariate analysis of a series of 165 patients of the French Cancer Center Federation Sarcoma Group.

BACKGROUND: Surgery is the main prognostic factor in retroperitoneal sarcoma. However, despite progress, surgery alone is rarely curative, and analysis of the causes of failures and of other prognostic factors are warranted to ascertain treatment orientations. METHODS: Data of patients treated from 1.80 to 12.94 for primary retroperitoneal sarcoma were extracted from the French Federation of Cancer Centers Sarcoma Group registry. Univariate and multivariate analysis were performed for initial local control and for local and general outcome. One hundred sixty-five patients (median age, 54 years; range, 16--82 years) were identified. Median tumor size was 15 cm (range, 2--70 cm); 31% of tumors presented with neurovascular or bone involvement. Liposarcoma, leiomyosarcoma, and malignant fibrous histiocytoma represented 66% of the tumors. Eighty-four percent of the tumors were of high or intermediate grade. Twenty patients had initial metastases. Multimodality treatment included surgery (150 patients), radiotherapy (92 patients), and chemotherapy (77 patients). Complete excision was achieved in 94 of 145 nonmetastatic patients. Median follow-up was 47 months (range, 3--160 months). RESULTS: Actuarial overall 5-year survival rate (median) was 46% (51 months). The main prognostic factors for survival were initial metastases and surgery, which represented the major treatment-linked factor. High-grade of tumors affected local recurrence, metastatic recurrence, and survival. Adjuvant radiotherapy was significantly associated with reduced local recurrence. Various evolutive patterns were observed with histologic subtypes. CONCLUSIONS: Aggressive surgery remains mandatory in retroperitoneal sarcoma, but a randomized trial is needed to evaluate the place of radiotherapy for local control.

Adolescent↗
PubMed2001

Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group.

BACKGROUND: Histologic grade is said to be the most important prognostic factor in adult soft tissue sarcomas (STS), but most grading systems have been tested in the overall sarcoma group and the predictive value of histologic grade needs to be assessed specifically for each of the histologic categories. METHODS: From 1980 to 1994, 1240 nonmetastatic patients were entered in the French STS database. The following parameters were studied: patient's age and gender, previous history, tumor location, size and depth, neurovascular or bone involvement (NBI), histologic type and subtype, and grade (the French Federation of Cancer Centers [FNCLCC] system). Median follow-up for the survivors was 88 months; only 5% of patients were lost to follow-up. The authors performed univariate and multivariate analyses for metastasis-free survival for the overall sarcoma group and for every main histologic type. RESULTS: In order of importance, parameters were respectively retained as independent predictors of metastasis as follows: grade, tumor size, NBI and tumor depth for the overall group, grade and NBI for malignant fibrous histiocytomas (n = 349), tumor size, histologic subtype and grade for liposarcomas (n = 188), NBI, grade and tumor size for leiomyosarcomas (n = 148), grade and NBI for synovial sarcomas (n = 125), grade for unclassified sarcomas (n = 140), and sarcomas of other types (n = 158). No parameter was significant for malignant schwannomas (n = 72) or for rhabdomyosarcomas (n = 60). CONCLUSION: In this study, histologic grade appeared as an independent predictor of metastasis development in the main histologic types of adult STS, with the exception of malignant schwannomas and rhabdomyosarcomas.

Adolescent↗
PubMed2001

Prognostic factors in localized primary synovial sarcoma: a multicenter study of 128 adult patients.

PURPOSE: To identify most significant and therapeutically relevant prognostic factors in adults with localized primary synovial sarcomas (SS) and to confirm the usefulness of the French Federation of Cancer Centers (FNCLCC) grading system, the prognostic impact of which has been already proven in soft tissue sarcomas. PATIENTS AND METHODS: Data on 128 patients with nonmetastatic SS collected from a cooperative database by the FNCLCC Sarcoma Group between 1980 and 1994 were studied retrospectively. Immunohistochemistry was performed at diagnosis in 77 cases (61%). The tumors were classified as biphasic (n = 45), monophasic fibrous (n = 72), and poorly differentiated (n = 10) subtypes. Histologic grade was determined according to the FNCLCC method, and vascular invasion was assessed in every case. RESULTS: The 5-year disease-specific survival (DSS) rate for this series of patients with localized SS was 62.9% (+/- 9.6% [SD]) with a median follow-up time of 37 months (range, 8 to 141 months). In multivariate analysis, the adverse risk factors associated with decreased DSS were International Union Against Cancer/American Joint Committee on Cancer stage III/IVA disease, male sex, and truncal tumor locations. For metastasis-free survival (MFS), disease stage III/IVA, tumor necrosis, and monophasic subtypes were the major factors associated with a less favorable prognosis. Separately, when not using disease stage, tumor necrosis, and mitotic activity, histologic grade became the most significant prognostic factor for both DSS and MFS. In addition, larger tumors and older patients become associated with a significantly worse prognosis. Independent adverse risk factors for local recurrence-free survival included histologic grade 3 and truncal tumor location. CONCLUSION: These data confirm that not all SS present the same severe outcome. High-risk patients identified on the basis of these parameters may qualify for an aggressive treatment approach.

Adult↗
PubMed2001

The detection of Tel-TrkC chimeric transcripts is more specific than TrkC immunoreactivity for the diagnosis of congenital fibrosarcoma.

The t(12;15)(p13;q25) translocation, a recurrent chromosomal abnormality of congenital fibrosarcoma, leads to the expression of a Tel-TrkC fusion transcript. To determine whether detection of the chimeric protein may be helpful for the diagnosis of congenital fibrosarcoma, immunohistochemistry was performed with an anti-TrkC antibody on 26 spindle cell tumours of newborn or young children (n=19) or adults (n=7). Four out of five congenital fibrosarcomas showed TrkC immunoreactivity with cytoplasmic paranuclear staining. However, TrkC immunoreactivity was not restricted to congenital fibrosarcoma and was observed in infantile myofibromatosis, congenital haemangiopericytoma, desmoid tumour, nodular fasciitis, fibrous hamartoma, inflammatory myofibroblastic tumour, and adult fibrosarcoma. RT-PCR analysis was performed on nine cases, including four congenital fibrosarcomas, for which frozen material was available. Tel-TrkC transcripts were detected by RT-PCR in the four congenital fibrosarcomas analysed, but not in the five other spindle cell tumours. Furthermore, several Tel-TrkC transcripts encoding for kinase isoforms of the Tel-TrkC protein were detected in congenital fibrosarcoma and may be involved in oncogenesis. The reciprocal TrkC-Tel transcript was detected in only one congenital fibrosarcoma. While the detection of a Tel-TrkC fusion transcript is a recurrent feature of congenital fibrosarcoma, TrkC immunoreactivity does not appear specific for the diagnosis of fibromatous paediatric tumours.

Adult↗
PubMed2001

ALK probe rearrangement in a t(2;11;2)(p23;p15;q31) translocation found in a prenatal myofibroblastic fibrous lesion: toward a molecular definition of an inflammatory myofibroblastic tumor family?

A prenatal tumor located in the lumbar paravertebral area was discovered during a routine ultrasound examination at 32 weeks of pregnancy and surgically removed at 4 months of life. The histopathological diagnosis was first suggested to be an infantile desmoid fibromatosis. The tumor karyotype showed a three-way translocation involving both chromosomes 2 and a chromosome 11, t(2;11;2)(p23;p15;q31). Fluorescence in situ hybridization with a probe flanking the ALK gene at 2p23 demonstrated a rearrangement, as previously described in inflammatory myofibroblastic tumors (IMTs). In light of the genetic analysis, the histopathological diagnosis was revised to IMT, although inflammatory cells were scarce. IMTs are pseudosarcomatous inflammatory lesions that primarily occur in the soft tissue and viscera of children and young adults. Our report describes for the first time the occurrence of IMT during prenatal life. The ALK rearrangement may represent the molecular definition of a subgroup of mesenchymal tumors, not always with complete morphological features of IMT, similar to the model of EWS rearrangement in the Ewing sarcoma family of tumors.

Adult↗
PubMed2001

A well-differentiated liposarcoma with a new type of chromosome 12-derived markers.

Well-differentiated liposarcomas (WDLPS) are cytogenetically characterized by the presence of supernumerary ring or giant rod marker chromosomes. These supernumerary chromosomes are composed of amplified sequences from chromosome 12 (12q14 approximately 15) in association with amplified segments from various other chromosomes, and contain alterations of the alpha satellite sequences. We report a case of WDLPS of the lipoma-like and sclerosing subtype that contains a novel type of supernumerary marker chromosome. Instead of rings or giant rods, these cells had three apparently identical copies of a subtelocentric supernumerary marker with a size and shape similar to C-group chromosomes. Fluorescence in situ hybridization analysis revealed that the markers were composed of amplified material from 12q14 approximately 15, including the genes MDM2 and CDK4. Similar to the rings and giant rods observed in other WDLPS cases, these unusual markers had no alpha satellite repeats at the primary constriction site, but centromeric activity could be demonstrated by using anti-centromere protein C antibodies. These findings show that the supernumerary markers of WDLPS may be variable in size and shape, but consistently share the same genomic structure, specifically 12q amplified sequences together with centromere alterations, and underline the importance of molecular methods in the diagnosis of adipose tissue tumors.

Aged↗
PubMed2001

Leiomyosarcomas and most malignant fibrous histiocytomas share very similar comparative genomic hybridization imbalances: an analysis of a series of 27 leiomyosarcomas.

Twenty-seven tumor samples with a diagnosis of leiomyosarcomas (LMS) were characterized by comparative genomic hybridization. The results were compared with immunohistochemical analysis of the smooth muscle profile of the tumors and expression of the RB1 gene protein. The comparative genomic hybridization profiles suggested that 7 of the 27 tumors might have been misclassified. High levels of DNA amplification were detected in 20 different small regions and recurrently involved bands 1p34, q21, 12q13-15, 17p, and 22q. Most recurrent simple gains were noted at sites such as 1p3, 1q21, 15q12-15, 16p, 17p and 17q, 19, 20q, 22q, and Xp. Significant losses of chromosome 13 were detected in 19 of the 27 tumors with a putative common region of loss in bands 13q14-21. Losses of chromosomes 1q, 2p and 2q, 4q, 9p, 10p and 10q, 11p and 11q23, and 16q were also highly recurrent. A comparative analysis between the most frequent genomic imbalances observed in this study of LMS and the genomic imbalances observed in a large proportion of malignant fibrous histiocytomas (MFH) from a previous study demonstrated that both types of tumors had similar recurrent imbalances. Although MFH were once thought to be a separate member of the soft tissue sarcoma family, our observations support the hypothesis that MFH are a morphologic modulation in the tumoral progression of other sarcomas, particularly LMS.

Adult↗