Monosomy 22 and trisomy 14 may be early events in the tumorigenesis of adult granulosa cell tumor.

The finding of monosomy 22 and trisomy 14 in a case of adult type of granulosa-thecoma cell tumor and the available information from the literature allow for the hypothesis that, especially monosomy 22, but also trisomy 14, may be early events in the tumorigenesis of adult sex cord-stromal tumors in general, and of granulosa-thecoma cell tumors in particular.     

HMG1 is not rearranged by 13q12 aberrations in lipomas.

Several cytogenetic subgroups with characteristic lesions involving chromosomal regions 12q14-15, 6p21.3, or 13q12 can be distinguished in lipomas. Rearrangements of the HMGIC gene have been described in cases with 12q14-15 abnormalities, whereas HMGIY has been shown to be the target gene of 6p21.3 aberrations. Recently, HMG1, another member of the HMG family, was mapped to 13q12. The aim of this study was to investigate the possible role of HMG1 aberrations in lipomas with 13q12 abnormalities. Two PAC clones containing HMG1 were isolated. By molecular cytogenetic investigations using these PAC clones and by Southern blot analysis of eight lipomas with 13q12 abnormalities, we were able to show that these chromosomal rearrangements did not result in intragenic rearrangements of HMG1 or breakpoints close to it.     

Cytogenetic analysis of 46 pleomorphic soft tissue sarcomas and correlation with morphologic and clinical features: A report of the CHAMP study group

With the aim of identifying objective cytogenetic-morphologic correlations, we evaluated 46 pleomorphic soft tissue sarcomas (mainly diagnosed originally as malignant fibrous histiocytomas) with clonal chromosome aberrations both cytogenetically and morphologically as part of an international collaborative study. By detailed histopathologic examination, most cases could be categorized into specific tumor types. Eight sarcomas were diagnosed as lipogenic (4 pleomorphic, 1 combined pleomorphic and myxoid/round cell, and 3 dedifferentiated liposarcomas), 19 as myogenic [11 leiomyosarcomas, 1 rhabdomyosarcoma, 4 myosarcomas not otherwise specified (NOS), and 3 probable myosarcomas NOS], 8 as myxofibrosarcomas, 1 as a malignant peripheral nerve sheath tumor, 1 as malignant mesenchymoma, 1 as extraskeletal osteosarcoma, 1 as sarcoma resembling proliferative fasciitis, and 7 as pleomorphic sarcomas NOS. In a three-grade system, 10 tumors were grade 2 and 36 were grade 3. The majority had highly complex karyotypes. A total of 24 recurrent abnormalities (defined by their presence in at least five cases) were detected: ring chromosomes, homogeneously staining regions (hsr) and/or double minute chromosomes (dmin), and structural rearrangement of 22 different chromosome bands or regions. The frequency and distribution of the recurrent karyotypic features were uneven. Grade 3 tumors displayed, on average, more aberrations per case than did grade 2 tumors. Nine of the selected abnormalities, including hsr/dmin and rearrangements of 19p13 and 19q13, were found only among the high-grade tumors. When the tumors were subdivided according to lineage of differentiation, the highest frequency of aberrations was seen in pleomorphic sarcomas NOS, followed by myxofibrosarcomas, myogenic sarcomas, and lipogenic sarcomas. None of the selected rearrangements was, however, specific for any of these subgroups. The sole consistent cytogenetic-morphologic association was that all three dedifferentiated liposarcomas had multiple abnormal clones, at least one of which contained supernumerary ring chromosomes. Due mainly to karyotype complexity, it therefore seems unlikely that cytogenetic analysis can assist in the differential diagnostic subclassification of pleomorphic sarcomas, nor was there any clear-cut indication that the karyotypic picture could be used to predict clinical outcome. Although the mean number of recurrent chromosome aberrations was almost twice as high in sarcomas that gave rise to metastases as among those that did not, no particular aberration was restricted to either of the two subgroups. Genes Chromosomes Cancer 22:16–25, 1998. © 1998 Wiley-Liss, Inc.     

Clonal chromosome abnormalities in a so‐called Dupuytren's subungual exostosis

We report the first cytogenetic investigation of a Dupuytren's subungual exostosis. The clonal abnormalities found suggest that at least some of these heterotopic ossifications could be neoplastic in nature, instead of being a purely reactive process or exuberant growth in response to trauma. Genes Chromosomes Cancer 24:162–164, 1999. © 1999 Wiley‐Liss, Inc.     

The t(1; 12)(p36;q13) in a Renal Oncocytoma

A new chromosome rearrangement, t(1;12)(p36;q13). is added to the cytogenetic changes found in renal oncocytomas. The breakpoint in 12q is cytogenetically different from those of the MAR region, and molecularly HMGlC located in 12q 15 on the basis of 3′ RACE experiments does not seem to be directly involved. Genes Chrornosorn Cancer l7:/36–/39 (1996). © 1996 Wiley-Lia, Inc.     

Cytogenetic and immunohistochemical evidence that giant cell fibroblastoma is related to dermatofibrosarcoma protuberans

From cytogenetic and immunohistochemical findings in a primary giant cell fibrosarcoma and its recurrence, it is further demonstrated that a close relationship exists between this tumor and dermatofibrosarcoma protuberans. Both tumors express CD34 and show rearrangements of chromosomes 17 and 22. Genes Chromosom Cancer 15:73–75 (1996). © 1996 Wiley-Liss, Inc.     

PTX3 in small‐vessel vasculitides: An independent indicator of disease activity produced at sites of inflammation

Objective

To verify whether the prototypical long pentraxin PTX3 represents an indicator of the activity of small‐vessel vasculitis.

Methods

Concentrations of PTX3, a pentraxin induced in endothelium by cytokines, were measured by enzyme‐linked immunosorbent assay in the sera of 43 patients with Churg‐Strauss syndrome, Wegener's granulomatosis, and microscopic polyangiitis. PTX3 was also measured in the sera of 28 patients with systemic lupus erythematosus (SLE), 22 with rheumatoid arthritis, and 16 with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). Serum concentrations of C‐reactive protein (CRP) were measured by immunoturbidimetry. The cells involved in PTX3 production in vivo were identified in skin biopsy samples.

Results

Patients with active vasculitis had significantly higher concentrations of PTX3 than did those with quiescent disease (P < 0.001). PTX3 levels in the latter group were similar to those in healthy controls. PTX3 levels were higher in patients with untreated vasculitis and lower in patients who underwent immunosuppressive treatments (P < 0.005). In contrast, patients with active SLE had negligible levels of the pentraxin. PTX3 levels did not correlate with CRP levels in vasculitis patients. Endothelial cells produced PTX3 in active skin lesions.

Conclusion

PTX3 represents a novel acute‐phase reactant produced at sites of active vasculitis.

     

Relief of inflammatory pain in rats by local use of the selective P2X7 ATP receptor inhibitor,oxidized ATP

Objective

Oxidized ATP (oATP) is a selective inhibitor of the P2Z/P2X7 ATP receptor for extracellular ATP, which contributes to the antinociceptive effect. This study sought to determine the mechanism by which local administration of oATP is able to relieve inflammatory pain in arthritic rat paws.

Methods

Arthritis was induced in Wistar rats by injections of Freund's complete adjuvant into one hind paw. Nociceptive thresholds were measured before and after local injection of oATP into the inflamed paws. The influence on pain transmission due to the presence of recruited inflammatory cells at the site of inflammation was determined by inhibiting the initial phase of their migration (by intravenous treatment with fucoidin, which blocks the adhesion molecules of the selectin family). ATP intraplantar content was determined in the different experimental conditions. Histologic features of the hind paws were evaluated by using the anti–P2X7 receptor polyclonal antibody.

Results

Intraplantar administration of oATP into inflamed paws significantly relieved inflammatory pain. The antinociceptive effect of oATP was independent of the immune‐cell recruitment. ATP levels in inflamed tissues were significantly reduced by oATP treatment. A variable presence of P2X7 receptors on cutaneous sensory nerves with respect to the different treatments was observed. Following oATP treatment, there was a reduction in P2X7 expression in the endings of peripheral nerves, as well as in endothelial cells.

Conclusion

Oxidized ATP inhibits inflammatory pain in arthritic rats by inhibition of the P2X7 receptor for ATP, which is localized on nerve terminals.