Philippe Terrier

Bio: Philippe Terrier is an academic researcher from Institut Gustave Roussy. The author has contributed to research in topics: Sarcoma & Soft tissue sarcoma. The author has an hindex of 55, co-authored 157 publications receiving 10057 citations.

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.

Abstract: 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. Cancer 2001;91:1914–26. © 2001 American Cancer Society.

MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: a comparative analysis of 559 soft tissue neoplasms with genetic data

Abstract: Atypical lipomatous tumor/well-differentiated liposarcoma (ALT-WDLPS) and dedifferentiated liposarcoma (DDLPS) may be difficult to distinguish from benign adipose tumors and from poorly differentiated sarcomas, respectively. Genetically, they are characterized by amplification of MDM2 and CDK4 genes on chromosome 12q13-15. We examined a series of 559 soft tissue tumors (44 ALT-WDLPS, 61 DDLPS, 49 benign adipose tumors, and 405 non-ALT-WDLPS/DDLPS sarcomas) for MDM2 and CDK4 expression using immunohistochemistry. MDM2 and CDK4 immunoexpressions were compared with gene amplification status (as assessed by quantitative PCR and/or comparative genomic hybridization) in 241 neoplasms. Most ALT-WDLPS/DDLPS expressed MDM2 (97%) and CDK4 (92%) as opposed to few benign adipose tumors (MDM2, 5%; CDK4, 2%) and a limited number of non-ALT-WDLSP/DDLPS sarcomas (MDM2, 19%; CDK4, 6%). The sensitivity and specificity of MDM2 and CDK4 immunostainings in identifying ALT-WDLPS/DDLPS among other soft tissue tumors were 97% and 92%, and 83% and 95%, respectively. MDM2 and CDK4 immunostainings were particularly useful to separate ALT-WDLPS from the large group of differentiated adipose tumors, and to distinguish DDLPS from poorly differentiated sarcomas. A strong correlation was observed between MDM2 and CDK4 stainings and gene amplification status. In conclusion, MDM2 and CDK4 immunostainings, which correlate with gene amplification, are helpful adjuncts to differentiate ALT-WDLPS from benign adipose tumors and to separate DDLPS from poorly differentiated sarcomas.

Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity

Abstract: Sarcomas are heterogeneous and aggressive mesenchymal tumors. Histological grading has so far been the best predictor for metastasis-free survival, but it has several limitations, such as moderate reproducibility and poor prognostic value for some histological types. To improve patient grading, we performed genomic and expression profiling in a training set of 183 sarcomas and established a prognostic gene expression signature, complexity index in sarcomas (CINSARC), composed of 67 genes related to mitosis and chromosome management. In a multivariate analysis, CINSARC predicts metastasis outcome in the training set and in an independent 127 sarcomas validation set. It is superior to the Federation Francaise des Centres de Lutte Contre le Cancer grading system in determining metastatic outcome for sarcoma patients. Furthermore, it also predicts outcome for gastrointestinal stromal tumors (GISTs), breast carcinomas and lymphomas. Application of the signature will permit more selective use of adjuvant therapies for people with sarcomas, leading to decreased iatrogenic morbidity and improved outcomes for such individuals.

Histologic Grade, But Not SYT-SSX Fusion Type, Is an Important Prognostic Factor in Patients With Synovial Sarcoma: A Multicenter, Retrospective Analysis

Abstract: Purpose To assess the prognostic value of SYT-SSX fusion type, in comparison with other factors, in a population of 165 patients with synovial sarcoma (SS). Patients and Methods Data on 165 patients with SS (141 with localized disease at diagnosis) were studied retrospectively. The following parameters were examined for their potential prognostic value: age at diagnosis, sex, tumor site (extremities v proximal/truncal), size, histology, mitotic count, necrosis, histologic grade (Federation Nationale des Centres de Lutte Contre le Cancer system), stage (1997 tumor-node-metastasis system classification), surgical margin status (assessed histologically), and fusion type (SYT-SSX1 v SYT-SSX2). Median follow-up time was 37 months (range, 2 to 302 months). Results Among those patients with localized disease at diagnosis, median and 5-year disease-specific survivals (DSS) for the SYT-SSX1 and SYT-SSX2 subgroups were 126 months and 67.4% versus 82 months and 63.2%, respectively (P = .12). Median and 5-year metast...

Prognostic Factors Influencing Progression-Free Survival Determined From a Series of Sporadic Desmoid Tumors: A Wait-and-See Policy According to Tumor Presentation

Abstract: Purpose Desmoid tumors are mesenchymal fibroblastic/myofibroblastic proliferations with locoregional aggressiveness and high ability to recur after initial treatment. We present the results of the largest series of sporadic desmoid tumors ever published to determine the prognostic factors of these rare tumors. Patients and Methods Four hundred twenty-six patients with a desmoid tumor at diagnosis were included, and the following parameters were studied: age, sex, delay between first symptoms and diagnosis, tumor size, tumor site, previous history of surgery or trauma in the area of the primary tumor, surgical margins, and context of abdominal wall desmoids in women of child-bearing age during or shortly after pregnancy. We performed univariate and multivariate analysis for progression-free survival (PFS). Results In univariate analysis, age, tumor size, tumor site, and surgical margins (R2 v R0/R1) had a significant impact on PFS. PFS curves were not significantly different for microscopic assessment of surgical resection quality (R0 v R1). In multivariate analysis, age, tumor size, and tumor site had independent values. Three prognostic groups for PFS were defined on the basis of the number of independent unfavorable prognostic factors (0 or 1, 2, and 3). Conclusion This study clearly demonstrates that there are different prognostic subgroups of desmoid tumors that could benefit from different therapeutic strategies, including a wait-and-see policy.

Integrative analysis of 111 reference human epigenomes

Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid Tumors

Abstract: The purpose of this article is to review the status and limitations of anatomic tumor response metrics including the World Health Organization (WHO) criteria, the Response Evaluation Criteria in Solid Tumors (RECIST), and RECIST 1.1. This article also reviews qualitative and quantitative approaches to metabolic tumor response assessment with 18 F-FDG PET and proposes a draft framework for PET Response Criteria in Solid Tumors (PERCIST), version 1.0. Methods: PubMed searches, including searches for the terms RECIST, positron, WHO, FDG, cancer (including specific types), treatment response, region of interest, and derivative references, were performed. Abstracts and articles judged most relevant to the goals of this report were reviewed with emphasis on limitations and strengths of the anatomic and PET approaches to treatment response assessment. On the basis of these data and the authors’ experience, draft criteria were formulated for PET tumor response to treatment. Results: Approximately 3,000 potentially relevant references were screened. Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria is widely applied but still has

Innate and adaptive immune cells in the tumor microenvironment

Abstract: Most tumor cells express antigens that can mediate recognition by host CD8(+) T cells. Cancers that are detected clinically must have evaded antitumor immune responses to grow progressively. Recent work has suggested two broad categories of tumor escape based on cellular and molecular characteristics of the tumor microenvironment. One major subset shows a T cell-inflamed phenotype consisting of infiltrating T cells, a broad chemokine profile and a type I interferon signature indicative of innate immune activation. These tumors appear to resist immune attack through the dominant inhibitory effects of immune system-suppressive pathways. The other major phenotype lacks this T cell-inflamed phenotype and appears to resist immune attack through immune system exclusion or ignorance. These two major phenotypes of tumor microenvironment may require distinct immunotherapeutic interventions for maximal therapeutic effect.