A subgroup of malignant fibrous histiocytomas is associated with genetic changes similar to those of well-differentiated liposarcomas

Chibon, Fréderic; Mariani, Odette; Derré, Josette; Malinge, Sébastien; Coindre, Jean Michél; Guillou, Louis; Lagacé, Réal; Aurias, Alain

doi:10.1016/s0165-4608(02)00614-3

Cited by 98 publications

(96 citation statements)

References 10 publications

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“…24 MDM2, a negative regulator of p53 was amplified in one of our phyllodes tumors cases. MDM2 is found to be frequently amplified in some sarcomas such as osteosarcomas, 46 liposarcomas, 47,48 'socalled' malignant histocytofibromas, 39,43 leiomyosarcomas 43 and neuroglial tumors. 49 The fact that in our This study has provided evidence that borderline and malignant phyllodes tumors could not be differentiated on the basis of the presence and of the number of chromosomal imbalances.…”

Section: Discussionmentioning

confidence: 99%

Phyllodes tumors of the breast segregate in two groups according to genetic criteria

et al. 2007

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Phyllodes tumors are rare fibroepithelial tumors of the breast. The pathologic grading of phyllodes tumors based on the aspect of the stromal component, is divided into 2 or 3 grades according to the system used. To determine whether genetic markers could be of use for improving the classification of phyllodes tumors and to provide a better knowledge of the genetic alterations in these tumors, we analyzed chromosomal changes detected by comparative genomic hybridization (CGH) in comparison with histological data, in a series of 30 cases. Recurrent chromosome imbalances were observed in 55, 91 and 100% of benign, borderline and malignant phyllodes tumors, respectively. The mean number of chromosome changes was one in benign, six in borderline, and six in malignant phyllodes tumors. Most frequent genetic imbalances were þ 1q (12/30), À13q (7/30), À6q (9/30), þ 5 (9/30) and À10p (8/30). Gains of 1q, present in only one of nine benign tumors, were found in 11/21 (51%) borderline or malignant tumors. Losses of 13q have 13q14.2 as smallest region of overlap, suggesting that the RB1 gene could be the target of deletions. Amplifications of 12q14, involving the MDM2 locus, and of 8p24, involving the MYC gene, were observed in one case each. Borderline and malignant phyllodes tumors could not be differentiated on the basis of their genomic imbalances (presence and number of chromosomal changes, presence of 1q gain and/or 13q loss). Conversely, benign tumors could be significantly differentiated from the group composed of borderline and malignant tumors (Po0.01). This study reveals two distinct patterns of genomic imbalance in phyllodes tumors: benign, with none or a few chromosome changes and malignant, with numerous recurrent chromosomal changes, in particular 1q gain and 13q loss. Helpful additional pathological criteria for differentiating the two genetic groups of phyllodes tumors are the nuclear size and the mitotic rate. Modern Pathology (2007) 20, 435-444.

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Section: Discussionmentioning

confidence: 99%

Phyllodes tumors of the breast segregate in two groups according to genetic criteria

et al. 2007

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“…[1][2][3] This last category is composed of tumors with high-level amplifications of chromosome 12 encompassing MDM2 and CDK4 loci (eg, well-differentiated and undifferentiated liposarcomas) (20% of cases) [3][4][5] and of tumors with very complex genomic imbalances (80% of cases), including mainly leiomyosarcomas and undifferentiated pleomorphic sarcomas. 4,5 Leiomyosarcomas correspond to 10-15% of softtissue sarcomas and display a strong smooth muscle differentiation. 6 They are frequently located in the retroperitoneum, and less frequently in the limbs.…”

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confidence: 99%

Smooth muscle differentiation identifies two classes of poorly differentiated pleomorphic sarcomas with distinct outcome

et al. 2014

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The clinical relevance of accurately diagnosing pleomorphic sarcomas has been shown, especially in cases of undifferentiated pleomorphic sarcomas with myogenic differentiation, which appear significantly more aggressive. To establish a new smooth muscle differentiation classification and to test its prognostic value, 412 sarcomas with complex genetics were examined by immunohistochemistry using four smooth muscle markers (calponin, h-caldesmon, transgelin and smooth muscle actin). Two tumor categories were first defined: tumors with positivity for all four markers and tumors with no or incomplete phenotypes. Multivariate analysis demonstrated that this classification method exhibited the strongest prognostic value compared with other prognostic factors, including histological classification. Secondly, incomplete or absent smooth muscle phenotype tumor group was then divided into subgroups by summing for each tumor the labeling intensities of all four markers for each tumors. A subgroup of tumors with an incomplete but strong smooth muscle differentiation phenotype presenting an intermediate metastatic risk was thus identified. Collectively, our results show that the smooth muscle differentiation classification method may be a useful diagnostic tool as well as a relevant prognostic tool for undifferentiated pleomorphic sarcomas.

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“…Chibon et al and Coindre et al have recently demonstrated that most of the malignant fibrous histiocytomas which develop in the retroperitoneum have these alterations. 15,16 Dedifferentiation is mostly considered a time-dependent phenomenon, and several reports have suggested the association between dedifferentiation and the altered expression of specific proteins. Overexpression of the proteins including MDM2 and CDK4, which are encoded by the genes located in the 12q13-15 region, is well described in liposarcoma, and dedifferentiated components exhibit a high level of MDM2-positive inmmunoreactivity in dedifferentiated liposarcomas.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, some authors have suggested that most retroperitoneal malignant fibrous histiocytomas have the possibility of actually being dedifferentiated liposarcomas. 15,16 Accordingly, we selected those cases of malignant fibrous histiocytoma where the tumors arose only in the extremities or the trunk. The diagnosis of all the malignant fibrous histiocytomas was confirmed by the panels of immunohistochemical study, since malignant fibrous histiocytoma is defined as an undifferentiated pleomorphic sarcoma which shows no distinct line of differentiation.…”

Section: Patients and Dna Extractionmentioning

confidence: 99%

Alterations of the RB1 gene in dedifferentiated liposarcoma

et al. 2005

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Dedifferentiated liposarcoma is a malignant adipocytic neoplasm containing a nonlipogenic sarcoma of variable histological grade that arises against the background of a pre-existing well-differentiated liposarcoma. The phenomenon of dedifferentiation is considered to be time-dependent, but the mechanism is not well known. The retinoblastoma protein, encoded by the RB1 gene located at 13q14, is a key regulator of proliferation, development, and differentiation of certain cell types, including adipocytes. In the current study, we investigated the genetic alterations of the RB1 gene, such as mutation (the essential promoter region and the protein-binding pocket domain; exons 20-24) and methylation of the promoter region, in addition to pRB expression and loss of heterozygosity (LOH) status, in two morphologically distinct areas (nonlipogenic dedifferentiated and well-differentiated components) in 27 patients. As a control, 11 undifferentiated high-grade pleomorphic sarcoma/pleomorphic malignant fibrous histiocytoma samples and 11 well-differentiated liposarcoma samples were also evaluated. Dedifferentiated components showed LOH (15/25; 60%) and abnormal retinoblastoma protein expression (18/27; 66.7%) more frequently than noted in the well-differentiated components (3/24; 12.5% and 9/27; 33.3%, respectively). Five and four out of the 27 dedifferentiated components harbored mutations and promoter methylation, respectively, whereas none of these alterations were seen in the well-differentiated components. These results suggest that retinoblastoma protein has a major role to play in dedifferentiation and that a 'two-hit' mechanism is involved in the altered retinoblastoma protein expression in dedifferentiated liposarcoma.

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A subgroup of malignant fibrous histiocytomas is associated with genetic changes similar to those of well-differentiated liposarcomas

Cited by 98 publications

References 10 publications

Phyllodes tumors of the breast segregate in two groups according to genetic criteria

Phyllodes tumors of the breast segregate in two groups according to genetic criteria

Smooth muscle differentiation identifies two classes of poorly differentiated pleomorphic sarcomas with distinct outcome

Alterations of the RB1 gene in dedifferentiated liposarcoma

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