Translocation and Expression of CSF1 in Pigmented Villonodular Synovitis, Tenosynovial Giant Cell Tumor, Rheumatoid Arthritis and Other Reactive Synovitides

Cupp, John S.; Miller, Mary Lou; Montgomery, Kelli; Nielsen, Torsten O.; O’Connell, John X.; Huntsman, David G.; Rijn, Matt van de; Gilks, C. Blake; West, Robert B.

doi:10.1097/pas.0b013e31802b86f8

Cited by 198 publications

(146 citation statements)

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“…Combined CSF1 immunohistochemistry and FISH demonstrated that only the cells with the translocation expressed CSF1 while the majority of cells neither carried the translocation nor expressed CSF1. Interestingly, Cupp et al, (2007) recently studied 57 cases of TGCT/PVNS; all were found to express CSF1 mRNA and/or CSF1 protein, including 22 cases (39%) that lacked the CSF1 translocation, suggesting that alternative mechanisms may lead to up-regulation of CSF1. Nevertheless, the COL6A3-CSF1 fusion transcripts identified in the present study are unlikely to produce a functional protein containing the receptor-binding part of CSF1, which is required for the mechanism described earlier.…”

Section: Discussionmentioning

confidence: 99%

Molecular identification of COL6A3‐CSF1 fusion transcripts in tenosynovial giant cell tumors

Möller

Mandahl

Mertens

et al. 2007

Genes Chromosomes & Cancer

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Tenosynovial giant cell tumors (TGCTs) are benign lesions of the tendon sheaths that primarily affect the fingers, ankles, or feet. Cytogenetic data have shown that 1p13 is most frequently involved in structural aberrations and that 2q37 is its most common translocation partner. The genes involved in the translocation t(1;2)(p13;q37) were recently identified: the colonystimulating factor-1 (CSF1 or M-CSF1) at 1p13 and the collagen type VI alpha-3 (COL6A3) at 2q37. Based upon the suggestion that a fusion of these genes through the translocation would result in overexpression of CSF1 due to a strong COL6A3 promoter, we performed RT-PCR on six TGCT cases with t(1;2) to search for a putative COL6A3-CSF1 fusion gene. Such fusion transcripts were detected in three cases of which one was an in-frame fusion. In all cases, however, the breakpoints in CSF1 appeared downstream of exon 5, indicating that the amino-terminal part of CSF1, which interacts with its receptor CSF1R, is not encoded by the the chimeric transcripts we identified. The pathogenetic mechanism of these chimeric transcripts is therefore unclear. V V C 2007 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Molecular identification of COL6A3‐CSF1 fusion transcripts in tenosynovial giant cell tumors

Möller

Mandahl

Mertens

et al. 2007

Genes Chromosomes & Cancer

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“…However, MRI effectively indicated bone lesions, articular cartilage lesions, and osteophytes in the joint cavity, which is helpful in determining whether arthroplasty is necessary. Therefore, we consider MRI to be useful in the diagnosis of PVNS and in determining the choice of surgical modalities, although pathological examination is needed in addition to MRI to accurately distinguish PVNS from rheumatoid arthritis, degenerative osteoarthropathy, synovial haemangioma, and other disorders [9].…”

Section: Discussionmentioning

confidence: 99%

Pigmented villonodular synovitis: a retrospective study of seventy five cases (eighty one joints)

Shi

Xia

et al. 2013

International Orthopaedics (SICOT)

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Purpose Pigmented villonodular synovitis (PVNS) is a relatively rare, benign proliferation lesion of the synovium of large joints, but there is not much information available about the disease's aetiology, clinical history, differential diagnosis, treatment, and long-term effects. We conducted a study to analyse these aspects of PVNS. Methods We reviewed all clinical data for 75 patients with PVNS (81 joints) who were treated either by synovectomy alone or synovectomy plus arthroplasty. Results In all cases, the diagnosis of PVNS was confirmed by pathological examination. The ratio of males to females was 27:48, and the average age of patients was 46 years (range, 15-80 years). Lesions were located in the knee, hip, or ankle, and pain and swelling were the main symptoms. Of 75 patients, 42 had a history of trauma to the involved joint. Forty-one patients (43 joints) underwent synovectomy alone, and 34 patients (38 joints) underwent synovectomy and arthroplasty together. Of the 75 patients, 61 had full follow-up data. Twelve patients had recurrent legions detected by pathological examinations; four patients had more than two recurrences. Moreover, five patients developed PVNS after arthroplasty. Conclusions PVNS occurs most often in middle-aged women and most frequently involves the knee, followed by the hip and ankle. The disease's etiology is varied and unclear. Surgical excision alone or with arthroplasty is an effective treatment, but there is a high rate of recurrence.

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“…Chromogenic RNA ISH was also used in these cases to assess CSF1 mRNA expression. The protocols for FISH and ISH have been previously described (11,17). The results of CSF1 break-apart FISH were determined by analyzing a minimum of 25 lesional cells, based on nuclear size and location within the tumor.…”

Section: Methodsmentioning

confidence: 99%

“…Accordingly, the aims of this study on the pathogenesis of malignant D-TSGCTs were 2-fold: first, by fluorescent in situ hybridization (FISH) and in situ hybridization (ISH), we investigated whether translocation and mRNA overexpression of the CSF1 gene also occur in malignant D-TSGCTs, as reported previously in benign TSGCTs (11,17). Second, we assessed whether malignant phenotypes of D-TSGCTs are attributed to the deregulated early G 1 and G 1 -S transition checkpoints and/or non -random chromosomal aberrations, like other tumors with a specific chimeric oncogene (e.g., Ewing sarcoma; ref.…”

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confidence: 99%

Immunohistochemical and Biogenetic Features of Diffuse-Type Tenosynovial Giant Cell Tumors: The Potential Roles of Cyclin A, P53, and Deletion of 15q in Sarcomatous Transformation

Huang

West

Tzeng

et al. 2008

Clinical Cancer Research

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Purpose: Diffuse-type tenosynovial giant cell tumor (D-TSGCT) is an aggressive proliferation of synovial-like mononuclear cells with inflammatory infiltrates. Despite the COL6A3-CSF1 gene fusion discovered in benign lesions, molecular aberrations of malignant D-TSGCTs remain unidentified. Experimental Design: We used fluorescent in situ hybridization and in situ hybridization to evaluate CSF1 translocation and mRNA expression in six malignant D-TSGCTs, which were further immunohistochemically compared with 24 benign cases for cell cycle regulators involving G 1 phase and G 1 -S transition. Comparative genomic hybridization, real-time reverse transcription-PCR, and a combination of laser microdissection and sequencing were adopted to assess chromosomal imbalances, cyclin A expression, and TP53 gene, respectively. Results: Five of six malignant D-TSGCTs displayed CSF1 mRNA expression by in situ hybridization, despite only one having CSF1translocation. Cyclin A (P = 0.008) and P53 (P < 0.001) could distinguish malignant from benign lesions without overlaps in labeling indices. Cyclin A transcripts were more abundant in malignant D-TSGCTs (P < 0.001). All malignant cases revealed a wild-type TP53 gene, which was validated by an antibody specifically against wild-type P53 protein.Chromosomal imbalances were only detected in malignant D-TSGCTs, with DNA losses predominating over gains. Notably, -15q was recurrently identified in five malignant D-TSGCTs, four of which showed a minimal overlapping deletion at 15q22-24. Conclusions: Deregulated CFS1 overexpression is frequent in malignant D-TSGCTs. The sarcomatous transformation involves aberrations of cyclin A, P53, and chromosome arm 15q. Cyclin A mRNA is up-regulated in malignant D-TSGCTs. Non^random losses at 15q22-24 suggest candidate tumor suppressor gene(s) in this region. However, P53 overexpression is likely caused by alternative mechanisms rather than mutations in hotspot exons.Tenosynovial giant cell tumors (TSGCT) are unique mesenchymal lesions that arise from the synovial lining of articular spaces, bursal sacs, and tendon sheaths (1, 2). The neoplastic property of TSGCTs has been supported by the identification of DNA aneuploidy and clonal karyotypic aberrations in these tumors, such as trisomies 7 and 5 and/or translocations involving chromosomal regions 1p11-13, 2q35-37, or 16q22-24 (2 -6). Given the difference in clinical behavior, TSGCTs are further divided by growth patterns into localized and diffuse types and by the predominant location of occurrence into extra-articular and intra-articular forms (1 -4). Histologically, diffuse-type TSGCT (D-TSGCT), i.e., pigmented villonodular synovitis if located intra-articularly, is an infiltrative proliferation of synovial-like mononuclear cells accompanied by heterogeneous inflammatory infiltrates among varying degrees of collagenous stroma (1, 2, 7). It frequently develops multiple local recurrences that are sometimes difficult to control by surgical excision and can severely compromise joint function...

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Translocation and Expression of CSF1 in Pigmented Villonodular Synovitis, Tenosynovial Giant Cell Tumor, Rheumatoid Arthritis and Other Reactive Synovitides

Cited by 198 publications

References 6 publications

Molecular identification of COL6A3‐CSF1 fusion transcripts in tenosynovial giant cell tumors

Molecular identification of COL6A3‐CSF1 fusion transcripts in tenosynovial giant cell tumors

Pigmented villonodular synovitis: a retrospective study of seventy five cases (eighty one joints)

Immunohistochemical and Biogenetic Features of Diffuse-Type Tenosynovial Giant Cell Tumors: The Potential Roles of Cyclin A, P53, and Deletion of 15q in Sarcomatous Transformation

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