RESUMEN
AIM: To evaluate if quantifying proton density fat fraction (PDFF) would be useful in separating lipoma, atypical lipomatous tumour (ALT) and liposarcoma in the extremities and trunk. In addition, differentiating ALT versus non-classical lipomas using magnetic resonance imaging (MRI)-based fatty acid composition (FAC) and three-dimensional (3D) texture analysis was tested. MATERIAL AND METHODS: This prospective study (undertaken between 2014-2017; comprising 20 women, 21 men) was approved by the Regional Ethical Review Board and informed consent was obtained from all participants. For PDFF and FAC 3D spoiled gradient multi-echo images were acquired. PDFF was analysed in 16 lipomas (25-76 years), 14 ALTs (42-78 years) and 11 myxoid liposarcomas (31-68 years). The difference of mean PDFF was tested with one-way analysis of variance. A support vector machine algorithm was used to find the separating mean PDFF values. RESULTS: Mean PDFF for lipomas was 90% (range 76-98%), for ALT 83% (range 62-91%), and for liposarcoma 4% (range 0-21%). The difference of mean PDFF for liposarcomas versus ALT and lipoma was significant (p=0.0001, for both), and for ALT versus lipoma (p=0.021). The optimal threshold for separating liposarcoma from ALT and lipoma was 41.5%, and for ALT and lipoma 85%. Texture analysis could not separate ALT and non-classical lipomas, while the difference for FAC unsaturation degree was significant (p=0.013). CONCLUSION: Measuring PDFF is a promising complement to standard MRI, to separate liposarcomas from ALT and lipomas. Lipomas that are not solely composed of fat cannot confidently be separated from ALT using PDFF, FAC, or texture analysis.
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Lipoma/diagnóstico por imagen , Liposarcoma/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ProtonesRESUMEN
Purpose. To determine the incidence of intra-articular synovial sarcomas and investigate if any radiological variables can differentiate them from localized (unifocal) pigmented villonodular synovitis (PVNS) and if multivariate data analysis could be used as a complementary clinical tool. Methods. Magnetic resonance images and radiographs of 7 cases of intra-articular synovial sarcomas and 14 cases of localized PVNS were blindedly reviewed. Variables analyzed were size, extra-articular growth, tumor border, blooming, calcification, contrast media enhancement, effusion, bowl of grapes sign, triple signal intensity sign, synovial low signal intensity, synovitis, age, and gender. Univariate and multivariate data analysis, the method of partial least squares-discriminant analysis (PLS-DA), were used. Register data on all synovial sarcomas were extracted for comparison. Results. The incidence of intra-articular synovial sarcomas was 3%. PLS-DA showed that age, effusion, size, and gender were the most important factors for discrimination between sarcomas and localized PVNS. No sarcomas were misclassified as PVNS with PLS-DA, while some PVNS were misclassified as sarcomas. Conclusions. The most important variables in differentiating intra-articular sarcomas from localized PVNS were age, effusion, size, and gender. Multivariate data analysis can be helpful as additive information to avoid a biopsy, if the tumor is classified as most likely being PVNS.
RESUMEN
Giant cell tumor of bone (GCTB) is characterized cytogenetically by frequent telomeric associations (tas). To explore the mechanisms behind the formation of tas in GCTB and to investigate their karyotypic consequences, the frequencies of tas and clonal aberrations other than tas in 20 GCTBs were compared to telomere length and status, as assessed by quantitative PCR, fluorescence in situ hybridization (FISH), and expression levels of four genes involved in telomere maintenance. Based on the G-banding results, the tumors were divided into two groups, one with a high frequency of tas and one with a low frequency. Clonal aberrations were found to be restricted to the group with a high level of tas, and the same group showed a significantly larger reduction in telomere length in tumor cells compared to peripheral blood cells. Furthermore, 65 out of 66 tas analyzed by FISH were negative for telomeric sequences. The expression levels of TERT, TERF1, TERF2, and POT1 did not correlate with telomere length or the frequency of tas. Thus, the present findings provide strong support for the notion that decreased telomere length is a prerequisite for tas in GCTBs and that the clonal changes occurring in GCTBs are derived from tas.
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Aberraciones Cromosómicas , Tumor Óseo de Células Gigantes/genética , Telómero/metabolismo , Adolescente , Adulto , Bandeo Cromosómico , Células Clonales , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Complejo Shelterina , Telomerasa/genética , Telomerasa/metabolismo , Proteínas de Unión a Telómeros/genética , Proteínas de Unión a Telómeros/metabolismo , Proteína 2 de Unión a Repeticiones Teloméricas/genética , Proteína 2 de Unión a Repeticiones Teloméricas/metabolismoRESUMEN
The EWSR1 gene is known to play a crucial role in the development of a number of different bone and soft tissue tumours, notably Ewing's sarcoma. POU5F1 is expressed during early development to maintain the totipotent status of embryonic stem and germ cells. In the present study, we report the fusion of EWSR1 and POU5F1 in two types of epithelial tumours: hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands. This finding not only broadens considerably the spectrum of neoplasms associated with EWSR1 fusion genes but also strengthens the evidence for shared pathogenetic mechanisms in the development of adnexal and salivary gland tumours. Reminiscent of the previously reported fusion genes involving EWSR1, the identified transcript is predicted to encode a chimeric protein consisting of the EWSR1 amino-terminal domain and the POU5F1 carboxy-terminal domain. We assessed the transcriptional activation potential of the chimera compared to the wild-type proteins, as well as activation of transcription through the oct/sox composite element known to bind POU5F1. Among other POU5F1 target genes, this element is present in the promoter of NANOG and in the distal enhancer of POU5F1 itself. Our results show that although the chimera is capable of significant transcriptional activation, it may in fact convey a negative regulatory effect on target genes.
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Adenoma de las Glándulas Sudoríparas/metabolismo , Proteínas de Unión a Calmodulina/genética , Carcinoma Mucoepidermoide/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/genética , Proteínas de Unión al ARN/genética , Glándulas Salivales/metabolismo , Neoplasias Cutáneas/metabolismo , Adulto , Mapeo Cromosómico , Cromosomas Humanos Par 22 , Cromosomas Humanos Par 6 , Femenino , Humanos , Hibridación Fluorescente in Situ , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/análisis , Proteínas de Fusión Oncogénica/genética , Embarazo , Proteína EWS de Unión a ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transfección/métodos , Translocación GenéticaRESUMEN
Previous studies have suggested that amplification of genes, notably the TOP2A gene, on chromosome arm 17q may be important for the development of malignant peripheral nerve sheath tumour (MPNST). In order to study the frequency, distribution, and chromosomal organization of rearrangements at 17q, interphase and metaphase fluorescence in situ hybridization (FISH) were used to evaluate copy number changes at 17q in 28 MPNSTs. Increased copy numbers were seen for the ERBB2 and TOP2A genes in eight and nine cases, respectively, supporting a potential role for these two genes in MPNST tumourigenesis. Net gain of distal 17q material was observed in 16 of the 28 MPNSTs, with high-level gain in three cases, and was associated with poor outcome. Among the 26 patients for whom follow-up data were available, gain of distal 17q was present in 11 of 12 tumours that had metastasized, compared with 4 of 14 of those that had not metastasized. Detailed FISH mapping analysis of metaphase spreads identified a 2 Mb commonly gained/amplified region at 17q25. Among the genes mapping to this region, BIRC5, which encodes the baculoviral IAP repeat-containing protein 5/survivin protein, is a strong candidate target gene for amplification, as it has been previously shown to be overexpressed in neurofibromatosis type 1-associated MPNST. Three other genes that co-amplified with BIRC5 represent other potential candidate genes: PTDSR involved in apoptosis; SEPT9 overexpressed in human malignant brain tumours; and SOCS3 involved in cell survival and differentiation of neurons.
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Cromosomas Humanos Par 17 , Genes Relacionados con las Neoplasias , Proteínas Asociadas a Microtúbulos/genética , Proteínas de Neoplasias/genética , Neoplasias de la Vaina del Nervio/genética , Sarcoma/genética , Adolescente , Adulto , Anciano , Niño , Bandeo Cromosómico , ADN-Topoisomerasas de Tipo II/genética , Femenino , Estudios de Seguimiento , Amplificación de Genes , Dosificación de Gen , Genes erbB-2 , Humanos , Hibridación Fluorescente in Situ , Proteínas Inhibidoras de la Apoptosis , Interfase , Masculino , Metafase , Persona de Mediana Edad , Neoplasias de la Vaina del Nervio/patología , Neoplasias de la Vaina del Nervio/secundario , Neurofibromatosis 1/genética , Neurofibromatosis 1/patología , Sarcoma/patología , Sarcoma/secundario , SurvivinAsunto(s)
Neoplasias Óseas/diagnóstico , Neoplasias Óseas/cirugía , Osteosarcoma/diagnóstico , Osteosarcoma/cirugía , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/cirugía , Biopsia con Aguja Fina , Humanos , Recuperación del Miembro , Neoplasias Pulmonares/cirugía , Imagen por Resonancia Magnética , Prótesis e Implantes , Estudios RetrospectivosAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Sarcoma de Ewing/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Neoplasias Óseas/radioterapia , Neoplasias Óseas/cirugía , Protocolos Clínicos , Humanos , Estudios Multicéntricos como Asunto , Análisis Multivariante , Pronóstico , Radioterapia Adyuvante , Ensayos Clínicos Controlados Aleatorios como Asunto , Sistema de Registros , Inducción de Remisión , Sarcoma de Ewing/mortalidad , Sarcoma de Ewing/radioterapia , Sarcoma de Ewing/cirugía , Análisis de Supervivencia , Resultado del TratamientoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Protocolos Clínicos , Supervivencia sin Enfermedad , Humanos , Interferón-alfa/uso terapéutico , Estudios Multicéntricos como Asunto , Osteosarcoma/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Países Escandinavos y NórdicosRESUMEN
In this study, a panel of 39 primary malignant fibrous histiocytomas (MFH) of high malignancy grade were characterised for chromosomal alterations. The results were then evaluated in relation to the survival and the occurrence of recurrent disease during follow-up for an average period of 63 months. Chromosomal alterations detected by comparative genomic hybridisation (CGH) were recorded in 37 of the 39 cases analysed. The most frequent CGH abnormalities were gains of 17p, 20q, 16p, 17q, 1p31, 7q21, and 9cen-q22, and losses of 9p21-pter and 13q21-22. However, the patterns of CGH imbalances did not allow the identification of a single common event, suggesting that the key initiating event(s) is not a numerical imbalance. Patients with tumours harbouring a gain of 17q showed significantly longer overall and disease-free survival (P=0.001 and 0.008) as well as lower frequency of metastasis (P=0.018) during follow-up. Taken together, the findings suggest that the clinical outcome of MFH is associated with the genetic profiles of the primary tumours. Importantly, a subgroup of MFHs characterised by a low risk of developing metastasis and local recurrence is recognised based on their frequent gains of 17q by CGH.
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Aberraciones Cromosómicas , Cromosomas Humanos Par 17/genética , Histiocitoma Fibroso Benigno/genética , Neoplasias de los Tejidos Blandos/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , ADN de Neoplasias/análisis , Supervivencia sin Enfermedad , Femenino , Histiocitoma Fibroso Benigno/patología , Humanos , Masculino , Metafase , Persona de Mediana Edad , Hibridación de Ácido Nucleico/genética , Pronóstico , Estudios Retrospectivos , Neoplasias de los Tejidos Blandos/patologíaRESUMEN
From 1990 to 1997, 113 eligible patients with classical osteosarcoma received neo-adjuvant chemotherapy consisting of high-dose methotrexate, cisplatin and doxorubicin. Good histological responders continued to receive the same therapy postoperatively, while poor responders received salvage therapy with an etoposide/ifosfamide combination. With a median follow-up of 83 months, the projected metastasis-free and overall survival rates at 5 years are 63 and 74%, respectively. Independent favourable prognostic factors for outcome were tumour volume < 190 ml, 24-h serum methotrexate > 4.5 microM and female gender. The etoposide/ifosfamide replacement combination did not improve outcome in the poor histological responders. In conclusion, this intensive multi-agent chemotherapy results in > 70% of patients with classical osteosarcoma surviving for 5 years. The data obtained from this non-randomised study do not support discontinuation and exchange of all drugs used preoperatively in histological poor responders. As observed in previous Scandinavian osteosarcoma studies, female gender appears to be a strong predictor of a favourable outcome.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Terapia Recuperativa , Adolescente , Adulto , Anciano , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Quimioterapia Adyuvante , Niño , Preescolar , Cisplatino/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Osteosarcoma/patología , Osteosarcoma/cirugía , Cooperación del Paciente , Pronóstico , Análisis de SupervivenciaRESUMEN
PURPOSE: The utility of fine needle aspiration cytology (FNAC) in conjunction with immunocytochemistry in the diagnosis of Ewing sarcoma and peripheral primitive neuroectodermal tumor, the Ewing family of tumors (EFT), is retrospectively described. PATIENTS AND METHODS: During a 10-year period 24 children and adolescents were diagnosed at Karolinska Hospital to have EFT of bone or soft tissue using FNAC. Criteria for diagnosis was based on cytomorphology combined with immunocytochemistry. The median age was 14.1 years (range 0.7-20.2). FNAC was performed within a median time of 1 day after referral. RESULTS: Forty aspiration procedures were performed, 24 at primary work up in 23 patients and 16 at suspected relapses in 10 patients. A primary cytologic diagnosis of EFT was obtained in 22 of 23 cases. In nine cases with primary disease there was no histologic confirmation. Two tumors were on FNAC diagnosed as neuroblastoma versus EFT, and EFT, respectively. Histopathology on resected tumor tissue from these patients showed EFT and small cell osteosarcoma, respectively. Suspected relapse was found to be positive at five and negative at 11 occasions. Immunocytochemistry was positive for CD45 (LCA) in 0/12, for desmin in 2/21, for MIC2 in 15/15, for NB84 in 1/3, for NFP in 7/7, for NSE in 12/18, for S-100 in 4/11 and for vimentin in 18/19. CONCLUSIONS: The results show that FNAC together with immunocytochemistry is a rapid, physically atraumatic and accurate method in diagnosing both primary EFT of bone and soft tissue as well as relapses.
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Neoplasias Óseas/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Tumores Neuroectodérmicos/diagnóstico , Sarcoma de Ewing/diagnóstico , Adolescente , Adulto , Biopsia con Aguja/normas , Neoplasias Óseas/patología , Niño , Preescolar , Femenino , Humanos , Inmunohistoquímica/normas , Lactante , Masculino , Recurrencia Local de Neoplasia/patología , Tumores Neuroectodérmicos/patología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sarcoma de Ewing/patologíaAsunto(s)
Síndrome del Compartimento Anterior/diagnóstico , Pierna/fisiopatología , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma no Hodgkin/diagnóstico , Dolor/diagnóstico , Adulto , Síndrome del Compartimento Anterior/etiología , Diagnóstico Diferencial , Femenino , Humanos , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma no Hodgkin/complicacionesRESUMEN
Giant-cell tumor of bone (GCT) is a locally aggressive neoplasm of unknown etiology and pathogenesis. Cytogenetically, no consistent chromosomal alterations, apart from telomeric associations involving various chromosome ends, have been described. Recently, however, it was reported that by using highly sensitive nested RT-PCR, a high proportion of GCT displays chimeric EWS/FLI1 fusion transcripts, i.e., the molecular genetic feature previously known to be strongly associated with the Ewing family of tumors. Thus, we decided to perform single-step and nested RT-PCR analyses on fresh frozen samples from 10 cases of GCT, all of which had also been subjected to cytogenetic analysis. After short-term culturing, none of the samples displayed any t(11;22)(q24;q12), the translocation characteristically giving rise to the EWS/FLI1 fusion, nor any other type of rearrangement of 11q24 or 22q12. Furthermore, in none of the cases did the RT-PCR analysis, whether single step or nested, result in products corresponding to a hybrid EWS/FLI1 transcript. On the basis of these results, we conclude that translocations leading to fusion of the EWS and FLI1 genes are not part of the pathogenesis of GCT.
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Neoplasias Óseas/genética , Tumores de Células Gigantes/genética , ARN Mensajero/metabolismo , Adulto , Bandeo Cromosómico , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 22 , ADN Complementario/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Proteína Proto-Oncogénica c-fli-1 , Proteína EWS de Unión a ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción/genética , Translocación GenéticaRESUMEN
Synovial sarcoma is an aggressive soft-tissue tumor that accounts for up to 10% of soft-tissue sarcomas. Cytogenetically, synovial sarcoma is characterized by the t(X;18)(p11;q11), found in more than 95% of the tumors. This translocation results in rearrangements of the SYT gene in 18q11 and one of the SSX1, SSX2, or SSX4 genes in Xp11, creating a SYT/SSX1, SYT/SSX2, or SYT/SSX4 chimeric gene. It has been shown that patients with SYT/SSX1 fusion genes have a shorter metastasis-free survival than do patients with SYT/SSX2. Previous studies have also suggested that clonal evolution may be associated with disease progression. In the present study, RT-PCR analysis showed that all 64 examined synovial sarcomas from 54 patients had SYT-SSX chimeric genes. SYT/SSX1 was found in 40 tumors from 33 patients, SYT/SSX2 in 23 tumors from 20 patients, and SYT/SSX4 in one case. Two patients had variant SYT/SSX2 transcripts, with 57 bp and 141 bp inserts, respectively, between the known SYT and SSX2 sequences. Patients with tumors with SYT/SSX1 fusions had a higher risk of developing metastases compared to those with SYT/SSX2 fusions (P = 0.01). The reciprocal transcripts SSX1/SYT and SSX2/SYT were detected using nested PCR in 11 of the 40 samples with SYT/SSX1 and 5 of the 23 samples with SYT/SSX2, respectively. Among 20 blood samples, SYT/SSX1 and SYT/SSX2 were detected in one sample each. The t(X;18), or variants thereof, was found cytogenetically in all patients but three. Among 32 primary tumors, the t(X;18) or a variant translocation was the sole anomaly in 10. In contrast, of the seven metastatic lesions that were investigated prior to radiotherapy, only one had a t(X;18) as the sole anomaly; all other tumors displayed complex karyotypes. Cytogenetic complexity in primary tumors was, however, not associated with the development of metastases. Tumors with SYT/SSX2 less often (4/12 vs. 7/15) showed complex karyotypes than did tumors with SYT/SSX1, but the difference was not significant. Combining cytogenetic complexity and transcript data, we found that the subgroup of patients with tumors showing simple karyotypes and SYT/SSX2 fusion had the best clinical outcome (2/8 patients developed metastases), and those with tumors showing complex karyotypes together with SYT/SSX1 fusion the worst (6/7 patients developed metastases). This corresponded to 5-year metastasis-free survival rates of 0.58 and 0.0, respectively (P = 0.02).
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Sarcoma Sinovial/genética , Neoplasias de los Tejidos Blandos/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Femenino , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteínas de Neoplasias/genética , Proteínas de Fusión Oncogénica/genética , Proteínas/genética , Proteínas Proto-Oncogénicas , Proteínas Represoras/genética , Sarcoma Sinovial/diagnóstico , Análisis de Secuencia de ADN , Neoplasias de los Tejidos Blandos/diagnósticoRESUMEN
Soft tissue sarcomas constitute a heterogeneous group of malignant tumors of mesenchymal origin, the classification of which may present a diagnostic challenge. We present here the cytological, histopathological, immunohistochemical, and cytogenetic findings of an unusual case of a highly aggressive sarcoma. Based on the morphology and the immunohistochemical profile, this primitive tumor and its metastases could not be conclusively classified as any of the defined subtypes of sarcomas, although the findings were suggestive of a variant of rhabdomyosarcoma. Cytogenetic characterization using G-banding, SKY, FISH, and CGH revealed almost identical chromosomal compositions of the primary tumor and the metastasis. The hypertetraploid karyotype was characterized by numerical imbalances as well as by an unbalanced translocation t(1;19)(q12;q13.2), which has not been previously reported.
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Cromosomas Humanos Par 19 , Cromosomas Humanos Par 1 , Mesenquimoma/genética , Translocación Genética , Amputación Quirúrgica , Biopsia con Aguja , Mapeo Cromosómico , Diagnóstico Diferencial , Finlandia , Pie , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Mesenquimoma/patología , Mesenquimoma/cirugía , Persona de Mediana Edad , Metástasis de la Neoplasia , Rabdomiosarcoma/genética , Rabdomiosarcoma/patología , Sarcoma/genética , Sarcoma/patología , Suecia , Población BlancaRESUMEN
PURPOSE: Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to stimulate fibroblasts to production of matrix metalloproteinases (MMPs). MMPs comprise a family of proteolytic enzymes implicated in the degradation of extracellular matrix which has been proposed to be one of the essential steps in tumor invasion and metastases. In the present study we investigated the expression and location of mRNAs for EMMPRIN, matrix metalloproteinase-2 (MMP-2), and membrane-type 1 matrix metalloproteinase (MT1-MMP) in mesenchymal tumors with different tendencies to recur or metastasize. SUBJECTS: Eight malignant fibrous histiocytomas (MFH), seven aggressive fibromatosis (AF), and six benign fibrous tumors (BF). METHOD: The mRNA-expression of EMMPRIN, MMP-2 and MT1-MMP were studied using mRNA in situ hybridization technique. RESULTS: The mRNA-expression of EMMPRIN, MMP-2 and MT1-MMP respectively were found at varying frequency and level in all tumor types. The mRNAs corresponding to EMMPRIN and MMP-2 were seen in neoplastic cells as well as in endothelial cells both inside and outside the tumor pseudo-capsule, whereas MT1-MMP was seen only within the tumors. The estimated mRNA levels of EMMPRIN and MMP-2 covariated significantly. Overall, the highest expression was found in the MFH tumors and the lowest levels in the BF tumors. DISCUSSION: These findings suggest that the MMP-inducer EMMPRIN and the extracellular matrix degrading system involving the metalloproteinases MMP-2 and MT1-MMP is frequently activated in mesenchymal tumors. The covariation between EMMPRIN and MMP-2 support previous findings that EMMPRIN may be an inducer of MMP-2. The high levels of MMP-2 mRNA in MFH indicate a relationship between the proteolytic activity of MMP-2 and the tumor aggressiveness.
RESUMEN
Combinations of radiotherapy and surgery are often used in local cancer treatments. Preoperative radiotherapy may delay wound healing after surgery. Chronic wounds are debilitating conditions that require frequent medical attention. Two patients suffering from chronic and slowly healing wounds post-surgery and preoperative radiotherapy are described. A significant acceleration of the healing by local injections with GM-CSF was demonstrated.
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Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Complicaciones Posoperatorias , Traumatismos por Radiación/tratamiento farmacológico , Dehiscencia de la Herida Operatoria/tratamiento farmacológico , Cicatrización de Heridas , Anciano , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Traumatismos por Radiación/inmunología , Sarcoma/radioterapia , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/radioterapia , Neoplasias de los Tejidos Blandos/cirugía , Dehiscencia de la Herida Operatoria/inmunologíaRESUMEN
Ionizing radiation is a well-known risk factor for sarcoma development. To investigate whether radiation-associated sarcomas are characterized by chromosome aberrations that distinguish them from de novo sarcomas, we identified those patients in our series of more than 500 cytogenetically abnormal sarcomas that fulfilled the following criteria: (1) each patient should have been irradiated for another malignancy at least 3 years prior to the sarcoma diagnosis, and (2) the sarcoma should have developed within the field of radiation. Ten patients fulfilling these criteria could be retrieved (median age at sarcoma diagnosis was 55 years, range 17-79; median latency period between primary tumor and radiation-associated sarcoma was 9 years, range 4-30). The diagnoses were typical for radiation-associated sarcomas: 2 each of malignant fibrous histiocytoma, leiomyosarcoma, and pleomorphic sarcoma, and 1 each of osteosarcoma, fibrosarcoma, myxofibrosarcoma, and spindle cell sarcoma. All 10 cases had relatively complex karyotypes with multiple, mostly unbalanced, structural rearrangements, similar to what has been reported in de novo sarcomas of the corresponding histologic subtypes. The only cytogenetic features that were unusually frequent among the radiation-associated sarcomas were the finding of unrelated clones in 3 cases, and loss of material from chromosome arm 3p, in particular 3p21-3pter, in 8 cases. Loss of the same chromosome segment has been described in 4 of the 8 previously published cases of radiation-associated sarcomas that have been analyzed after short-term culturing, which makes this imbalance significantly (P < 0.001) more frequent among radiation-associated sarcomas (12 of 18 cases) than among unselected cases of the corresponding histologic subtypes (74 of 282 cases). In contrast to the cytogenetic results, no 3p deletions were detected among the 6 cases of the present series that could be analyzed by comparative genomic hybridization (CGH). The most frequent imbalance detected by CGH was gain of 15cen-q15 (3 cases), followed by loss of chromosome 13 and gain of 5p, and 7cen-q22, each detected in 2 cases.