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BACKGROUND: Osteosarcomas (OS) in the craniomaxillofacial (CMF) region are typically diagnosed at later age than long-bone OS, but they are reported to have better 5-year survival. Curative treatment warrants wide surgical resection, which is often not possible in the CMF region. The purpose of this article is to present a nationwide series of CMF in Finland to discuss the role of surgery. PATIENTS AND METHODS: All 21 CMF OS patients managed in Finland from 1992 to 2009 were included. The mean age was 40 years (range 15-72). Data on patient and tumor characteristics, treatment modalities, and survival were recorded. All patients had a minimum follow-up of 5 years or until death. RESULTS: OS was evenly represented in the mandible and maxillary bones, which together constituted 76% of all sites. Surgery with curative intent was carried out in 20 patients. Clear margins were achieved in only five cases. Eight (40%) of these 20 patients died due to OS, and their average survival time was 1.3 years. Seven (35%) out of the 20 patients received radiotherapy due to close/intralesional surgical margins, and four of them did not develop recurrences during the follow-up. CONCLUSIONS: The results suggest that postoperative radiotherapy may alter the prognosis in CMF OS, particularly in cases with close or intralesional margins. This may increase the survival rates achieved by prompt action in performing radical surgery.
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Neoplasias Óseas , Osteosarcoma , Adolescente , Adulto , Anciano , Neoplasias Óseas/cirugía , Finlandia , Humanos , Márgenes de Escisión , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Osteosarcoma/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response. PATIENTS AND METHODS: Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken. RESULTS: Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3-4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen. CONCLUSIONS: New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Adolescente , Neoplasias Óseas/cirugía , Niño , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Terapia Neoadyuvante , Osteosarcoma/cirugía , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Calidad de Vida , Proyectos de Investigación , Adulto JovenRESUMEN
BACKGROUND: Prokineticin-1 (PROK1) and prokineticin-2 (PROK2) are chemokine-like proteins that may influence cancer growth by regulating host defence and angiogenesis. Their significance in viral infection-associated cancer is incompletely understood. We studied prokineticins in Merkel cell carcinoma (MCC), a skin cancer linked with Merkel cell polyomavirus (MCPyV) infection. METHODS: Carcinoma cell expression of PROK1 and PROK2 and their receptors (PROKR1 and PROKR2) was investigated with immunohistochemistry, and tumour PROK1 and PROK2 mRNA content with quantitative PCR from 98 MCCs. Subsets of tumour infiltrating leukocytes were identified using immunohistochemistry. RESULTS: Merkel cell polyomavirus-positive MCCs had higher than the median PROK2 mRNA content, whereas MCPyV-negative MCCs contained frequently PROK1 mRNA. Cancers with high tumour PROK2 mRNA content had high counts of tumour infiltrating macrophages (CD68+ and CD163+ cells). Patients with higher than the median PROK2 mRNA content had 44.9% 5-year survival compared with 23.5% among those with a smaller content (hazard ratio (HR): 0.53; 95% confidence interval (CI): 0.34-0.84; P=0.005), whereas the presence of PROK1 mRNA in tumour was associated with unfavourable survival (P=0.052). CONCLUSIONS: The results suggest that prokineticins are associated with MCPyV infection and participate in regulation of the immune response in MCC, and may influence outcome of MCC patients.
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Carcinoma de Células de Merkel/metabolismo , Carcinoma de Células de Merkel/virología , Hormonas Gastrointestinales/metabolismo , Neuropéptidos/metabolismo , Infecciones por Polyomavirus/metabolismo , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/virología , Factor de Crecimiento Endotelial Vascular Derivado de Glándula Endocrina/metabolismo , Adulto , Carcinoma de Células de Merkel/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Infecciones por Polyomavirus/patología , Infecciones por Polyomavirus/virología , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Péptidos/metabolismo , Neoplasias Cutáneas/patología , Análisis de Supervivencia , Análisis de Matrices TisularesRESUMEN
BACKGROUND: The asymmetric laterality of UV-linked skin cancer, including melanoma and non- melanoma skin cancers has been identified. However, there seems to be a paucity in the data correlating the laterality and presence of Merkel cell polyoma virus (MCPyV) DNA as an aetiological factor for this phenomenon. OBJECTIVE: To study the laterality in Finnish primary Merkel cell carcinoma (MCC) patients, and compare statistically clinicopathological variables with lateral distribution. METHODS: Data on 171 primary MCC patients and tumour characteristics; and the presence of MCPyV DNA or large T antigen in the tumour tissue, MCPyV copy number and MCC specific mortality were compared statistically against left, right or midline presentation. RESULTS: Fiftysix percentage of tumours presented on the left, 37% on the right and 7% in the midline. Excluding the latter category, the left-sided excess was 60%. The excess of left-sided tumours was noted in head and neck with left-right ratio 3.22, face 1.5, forearm and hand 4.0 and the leg and foot 2.4. On the trunk, tumours occurred equally on both sides. Statistically significant difference was noted for smaller midline tumours (P < 0.0065). Left-sided tumours associated with lower median Merkel cell polyoma virus copy number (P < 0.042) although the trend vanished when comparing the groups separately. CONCLUSION: We confirmed left-sided asymmetry in MCC distribution. In areas commonly hidden form solar exposure, the occurrence was symmetrical. Detailed aetiology of these findings remains unclear, plausible explanations include biology of viral associated tumours or alterations in Nodal transcription factor pathway.
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Carcinoma de Células de Merkel/patología , Neoplasias Cutáneas/patología , Anciano , Estudios de Cohortes , Femenino , Finlandia , Humanos , MasculinoRESUMEN
BACKGROUND: Mediator complex participates in transcriptional regulation by connecting regulatory DNA sequences to the RNA polymerase II initiation complex. Recently, we discovered through exome sequencing that as many as 70% of uterine leiomyomas harbour specific mutations in exon 2 of mediator complex subunit 12 (MED12). In this work, we examined the role of MED12 exon 2 mutations in other tumour types. METHODS: The frequency of MED12 exon 2 mutations was analysed in altogether 1158 tumours by direct sequencing. The tumour spectrum included mesenchymal tumours (extrauterine leiomyomas, endometrial polyps, lipomas, uterine leiomyosarcomas, other sarcomas, gastro-intestinal stromal tumours), hormone-dependent tumours (breast and ovarian cancers), haematological malignancies (acute myeloid leukaemias, acute lymphoid leukaemias, myeloproliferative neoplasms), and tumours associated with abnormal Wnt-signalling (colorectal cancers (CRC)). RESULTS: Five somatic alterations were observed: three in uterine leiomyosarcomas (3/41, 7%; Gly44Ser, Ala38_Leu39ins7, Glu35_Leu36delinsVal), and two in CRC (2/392, 0.5%; Gly44Cys, Ala67Val). CONCLUSION: Somatic MED12 exon 2 mutations were observed in uterine leiomyosarcomas, suggesting that a subgroup of these malignant tumours may develop from a leiomyoma precursor. Mutations in CRC samples indicate that MED12 may, albeit rarely, contribute to CRC tumorigenesis.
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Neoplasias Colorrectales/genética , Leiomiosarcoma/genética , Complejo Mediador/genética , Neoplasias Uterinas/genética , Neoplasias Colorrectales/patología , Exoma , Exones , Femenino , Humanos , Leiomioma/genética , Leiomioma/patología , Leiomiosarcoma/patología , Mutación , Análisis de Secuencia de ADN/métodos , Neoplasias Uterinas/patologíaRESUMEN
BACKGROUND: We developed a web-based, prognostic tool for extremity and trunk wall soft tissue sarcoma to predict 10-year sarcoma-specific survival. External validation was performed. METHODS: Patients referred during 1987-2002 to Helsinki University Central Hospital are included. External validation was obtained from the Lund University Hospital register. Cox proportional hazards models were fitted with the Helsinki data. The previously described model (SIN) includes size, necrosis, and vascular invasion. The extended model (SAM) includes the SIN factors and in addition depth, location, grade, and size on a continuous scale. Models were statistically compared according to accuracy (area under the ROC curve=AUC) of 10-year sarcoma-specific survival prediction. RESULTS: The AUC of the SAM model in 10-year survival prediction in the Helsinki patient series was 0.81 as compared with 0.74 for the SIN model (P=0.0007). The corresponding AUCs in the external validation series were 0.77 for the SAM model and 0.73 for the SIN model (P=0.03). A web-based calculator for the SAM model is available at http://www.prognomics.org/sam. CONCLUSION: Addition of grade, depth, and location as well as tumour size on a continuous scale significantly improved the accuracy of the prognostic model when compared with a model that includes only size, necrosis, and vascular invasion.
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Sistemas en Línea , Sarcoma/diagnóstico , Neoplasias de los Tejidos Blandos/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Calibración , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Sarcoma/mortalidad , Sarcoma/patología , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/terapia , Carga Tumoral , Adulto JovenRESUMEN
The purpose of this study was to investigate the surgical management of radiation-associated cutaneous breast angiosarcoma with an emphasis on surgical margins and choice of reconstruction. Nine cases of angiosarcoma were identified in patients earlier treated with radiotherapy for breast cancer. Breast angiosarcoma was diagnosed a median of 5.25 years following radiotherapy. Median age at diagnosis was 60 years. Surgical treatment consisted of radical mastectomy (four cases), simple mastectomy (two cases) and wide local excision (three cases). Defect reconstruction involved three latissimus dorsi flap reconstructions and four skin grafts. Clear histological margins were achieved in all cases. Median follow-up was 81 months. Six patients were alive and disease-free at the end of the study period. Aggressive surgical resection with wide margins is essential to reduce local recurrence and improve survival.
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Neoplasias de la Mama/cirugía , Hemangiosarcoma/cirugía , Neoplasias Inducidas por Radiación/cirugía , Neoplasias Cutáneas/cirugía , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/etiología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/radioterapia , Femenino , Hemangiosarcoma/etiología , Hemangiosarcoma/mortalidad , Humanos , Mastectomía , Persona de Mediana Edad , Músculo Esquelético/trasplante , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Neoplasias Inducidas por Radiación/mortalidad , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/mortalidad , Trasplante de Piel , Colgajos QuirúrgicosRESUMEN
AIMS: Limb-sparing surgery combined with radiotherapy (RT) is the basis of extremity soft tissue sarcoma (STS) treatment. The aim of this study was to evaluate the results of microvascular reconstruction after extensive tumour resections in the upper extremity. METHODS: Twenty patients with STS of the upper extremity were treated with excision and microvascular reconstruction. RT was administered if surgical margins were less than 25 mm. Results were evaluated retrospectively. RESULTS: Twenty free flaps were performed and no flaps were lost. There was no operative mortality, and wound complication rate was 15%. Median follow-up length was 74 months. Five-year local recurrence-free survival was 57%, metastasis-free survival 67%, disease-free survival 45% and disease-specific overall survival 80%. Ten patients had no or only mild impairment of upper extremity function, seven had impaired function affecting daily life, and three patients underwent amputation. For patients treated with curative intent, limb salvage rate was 94%. CONCLUSIONS: Free flaps are useful and reliable in the treatment of patients with STS of the upper extremity. Without microvascular reconstruction limb salvage would have been impossible in these patients. Oncological outcome is comparable to other extremity STS patients and upper extremity function is acceptable.
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Recuperación del Miembro , Microcirugia , Microvasos/cirugía , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/cirugía , Colgajos Quirúrgicos/irrigación sanguínea , Extremidad Superior , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Procedimientos de Cirugía Plástica , Sarcoma/radioterapia , Sarcoma/secundario , Neoplasias de los Tejidos Blandos/radioterapiaRESUMEN
BACKGROUND: Immunosuppression and Merkel-cell polyomavirus (MCPyV) infection may have a role in the pathogenesis of Merkel-cell carcinoma (MCC), a rare neuroendocrine carcinoma of the skin. METHODS: We studied incidence of chronic lymphocytic leukaemia (CLL) and MCC from the files of the Finnish Cancer Registry and the largest hospital of Finland, Helsinki University Central Hospital, from 1979 to 2006. Presence of MCPyV DNA in MCCs was investigated by quantitative PCR. RESULTS: We identified 4164 patients diagnosed with CLL and 172 diagnosed with MCC. Six patients diagnosed with both diseases were found; CLL was the first diagnosis in four cases and MCC in two. The standardised incidence ratio (SIR) for CLL after the diagnosis of MCC was highly elevated, 17.9 (95% confidence interval (CI), 2.2-64.6; P<0.001), and the SIR for MCC after the diagnosis of CLL was also elevated, 15.7 (3.2-46.0, P<0.01). Merkel-cell polyomavirus DNA was present in all five MCCs with tumour tissue available for analysis. CONCLUSIONS: We conclude that patients diagnosed with CLL have a substantially increased risk for MCC, and vice versa. Merkel-cell polyomavirus DNA is frequently present in MCCs that occur in CLL patients. Immunosuppression related with CLL and viral infection might explain the association between CLL and MCC.
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Carcinoma de Células de Merkel/etiología , Leucemia Linfocítica Crónica de Células B/complicaciones , Células de Merkel/virología , Poliomavirus/aislamiento & purificación , Anciano , Anciano de 80 o más Años , Carcinoma de Células de Merkel/virología , ADN Viral/análisis , Femenino , Humanos , Terapia de Inmunosupresión , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: Limb-sparing surgery and satisfactory functional outcome is the goal of extremity soft tissue sarcoma (STS) surgery. Tissue defects after tumour excision are often extensive, and microvascular reconstruction is frequently required. METHODS: Seventy-three patients with STS of the leg requiring microvascular reconstruction were treated between 1985 and 2006. Radiotherapy was delivered if the microscopic surgical margin was less than 2.5 cm. RESULTS: Mean follow-up was 65.9 months. Seventy-five free flaps were performed, with a success rate of 95 per cent. One patient died within a month of surgery. Five-year local recurrence-free survival was 82 per cent, metastasis-free survival 59 per cent, disease-free survival 56 per cent and disease-specific overall survival 70 per cent. Fifty-five (75 per cent) of the 73 patients were able to walk normally or had only minor walking impairment. CONCLUSION: Without microvascular reconstruction, amputation would have been necessary in most patients. Microvascular reconstruction is safe and reliable in lower extremity STS reconstruction.
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Complicaciones Posoperatorias/etiología , Sarcoma/cirugía , Neoplasias Cutáneas/cirugía , Colgajos Quirúrgicos/irrigación sanguínea , Procedimientos Quirúrgicos Vasculares/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica/mortalidad , Amputación Quirúrgica/estadística & datos numéricos , Supervivencia sin Enfermedad , Femenino , Humanos , Pierna , Tiempo de Internación , Masculino , Microcirculación , Persona de Mediana Edad , Metástasis de la Neoplasia , Complicaciones Posoperatorias/mortalidad , Factores de Riesgo , Sarcoma/mortalidad , Neoplasias Cutáneas/mortalidad , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/mortalidad , Adulto JovenRESUMEN
BACKGROUND: The aim was to review a single-institution experience of a prospective treatment protocol for soft tissue sarcoma of the extremity and trunk wall, with particular focus on the smallest surgical margin leading to local control. METHODS: The study included 270 patients who had surgery for soft tissue sarcoma at Helsinki University Central Hospital between 1987 and 1997. Resection margins were measured prospectively from tumour specimens. Radiotherapy was administered if the smallest margin measured less than 2.5 cm, irrespective of tumour grade. RESULTS: With a median follow-up of 6.6 years, the 5-year local control rate was 76.4 per cent. On multivariable analysis, the smallest surgical margin around the sarcoma (after radiotherapy) was prognostic for local control. A margin of at least 2.5 cm was associated with a local recurrence-free rate of 89.2 per cent at 5 years. Tumour size, depth or grade and patient's age had no independent prognostic effect on local control. CONCLUSION: Surgical margin had independent prognostic value for local control. A surgical margin of 2-3 cm provided reasonable local control of soft tissue sarcoma, even without radiotherapy. Radiotherapy is recommended for smaller margins, irrespective of tumour grade.
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Neoplasias de Tejido Conjuntivo/cirugía , Sarcoma/cirugía , Pared Abdominal , Adulto , Anciano , Amputación Quirúrgica/estadística & datos numéricos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos Clínicos , Extremidades , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Neoplasias de Tejido Conjuntivo/tratamiento farmacológico , Neoplasias de Tejido Conjuntivo/radioterapia , Estudios Prospectivos , Radioterapia Adyuvante , Sarcoma/tratamiento farmacológico , Sarcoma/radioterapia , Resultado del TratamientoRESUMEN
The amplification or gain of the p-arm of chromosome 17 is common in sarcomas, suggesting its role in carcinogenesis. Here, we report the architectural structure and targets of 17p aberrations commonly shared by osteosarcoma (OS), leiomyosarcoma (LMS) and malignant fibrous histiocytoma (MFH) of soft tissue. Two low-grade and two high-grade soft tissue LMS, three OS, and two MFH samples were studied using fine-resolution oligonucleotide-based microarray comparative genomic hybridization. Eight of the nine samples showed a loss of 17pter-->p13, the locus of tumor suppressor TP53 preceding the amplified area 17p12-->p11.2. The size and detailed architecture of the amplified region of 17p differed between the studied sarcoma entities. OS and high-grade LMS showed similar complex patterns of discontinuous amplifications with regions of gain in between. MFH and low-grade LMS showed continuous regions of gains and amplifications. Precise boundaries of the lost or gained regions were determined, and in addition to the previously suggested targets of the region, ELAC and FLCN were amplified in all the sarcoma entities.
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Cromosomas Humanos Par 17/genética , ADN de Neoplasias/genética , Genoma Humano/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Sarcoma/genética , Proteína p53 Supresora de Tumor/deficiencia , Proteína p53 Supresora de Tumor/genética , Adolescente , Adulto , Anciano de 80 o más Años , Femenino , Amplificación de Genes/genética , Dosificación de Gen , Genes Relacionados con las Neoplasias/genética , Humanos , Masculino , Persona de Mediana Edad , Hibridación de Ácido Nucleico , Programas InformáticosAsunto(s)
Mixoma/patología , Complicaciones Neoplásicas del Embarazo/patología , Neoplasias Retroperitoneales/patología , Adulto , Nalgas , Femenino , Humanos , Recién Nacido , Laparotomía , Nacimiento Vivo , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mixoma/cirugía , Invasividad Neoplásica , Embarazo , Complicaciones Neoplásicas del Embarazo/cirugía , Neoplasias Retroperitoneales/cirugía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , UltrasonografíaRESUMEN
Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing, low-grade dermal tumor. Cytogenetic and FISH studies have revealed that the chromosomal rearrangements characteristic of DFSP tumors involve both translocations and the formation of a supernumerary ring derived from chromosomes 17 and 22. The t(17;22) (q22;q13.1) translocation generates a gene fusion between COL1A1 and PDGFB, which serves as a diagnostic marker of DFSP. In the present study we performed array-CGH (aCGH) analysis on ten DFSP tumors. The COL1A1 region at 17q was gained in 71% (5/7) of the samples and the PDGFB region at 22q was gained in 43% (3/7) of the individual samples. In addition to the 17q and 22q gains, altogether 17 minimal common regions of gain and one region of loss were detected.
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Biología Computacional/métodos , Dermatofibrosarcoma/genética , Hibridación de Ácido Nucleico/métodos , Neoplasias Cutáneas/genética , Adulto , Cromosomas/ultraestructura , Colágeno Tipo I/genética , Cadena alfa 1 del Colágeno Tipo I , Análisis Citogenético/métodos , Femenino , Dosificación de Gen , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/metabolismo , Translocación GenéticaAsunto(s)
Carcinoma de Células de Merkel/secundario , Antígeno Ki-67/análisis , Neoplasias Cutáneas/patología , Carcinoma de Células de Merkel/química , Proliferación Celular , Progresión de la Enfermedad , Humanos , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Pronóstico , Neoplasias Cutáneas/químicaRESUMEN
DNA copy number amplifications activate oncogenes and are hallmarks of nearly all advanced tumors. Amplified genes represent attractive targets for therapy, diagnostics and prognostics. To investigate DNA amplifications in different neoplasms, we performed a bibliomics survey using 838 published chromosomal comparative genomic hybridization studies and collected amplification data at chromosome band resolution from more than 4500 cases. Amplification profiles were determined for 73 distinct neoplasms. Neoplasms were clustered according to the amplification profiles, and frequently amplified chromosomal loci (amplification hot spots) were identified using computational modeling. To investigate the site specificity and mechanisms of gene amplifications, colocalization of amplification hot spots, cancer genes, fragile sites, virus integration sites and gene size cohorts were tested in a statistical framework. Amplification-based clustering demonstrated that cancers with similar etiology, cell-of-origin or topographical location have a tendency to obtain convergent amplification profiles. The identified amplification hot spots were colocalized with the known fragile sites, cancer genes and virus integration sites, but global statistical significance could not be ascertained. Large genes were significantly overrepresented on the fragile sites and the reported amplification hot spots. These findings indicate that amplifications are selected in the cancer tissue environment according to the qualitative traits and localization of cancer genes.
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ADN de Neoplasias/genética , Amplificación de Genes , Neoplasias/genética , Daño del ADN , Humanos , Hibridación de Ácido NucleicoRESUMEN
A novel bioabsorbable composite membrane of polyethylene oxide terephthalate and polybutylene terephthalate copolymer (Polyactive 70/30) combined with bioactive glass No. 13--93 was tested in the repair of experimental maxillary alveolar cleft defects. In this pilot study, the possible ability of the membrane to promote bone formation by guided tissue regeneration was investigated. Standard alveolar defects were made bilaterally in the maxilla of 12 growing rabbits and were filled with autogenous bone grafts. The test defect was covered with the composite membrane and the other defect was left uncovered to serve as a control. The follow-up time was 10 weeks. Radiological, histological, and histomorphometric evaluations were performed. Radiologically, no statistically significant differences between test and control defects at 10 weeks were found. Histologically, the membrane enhanced osteogenic activity locally at the membrane-bone interface. Swelling of the membrane was observed. Histomorphometrically, no significant promotion of bone formation by the membrane was observed. The composite membrane was found to be biocompatible and surgically easy to use, but its osteopromotive effect was limited in this experimental cleft model. Further studies are necessary to assess its suitability for reconstructive surgical applications.
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Proceso Alveolar/cirugía , Materiales Biocompatibles/química , Fisura del Paladar/patología , Fisura del Paladar/cirugía , Resinas Compuestas/química , Vidrio/química , Proceso Alveolar/patología , Animales , Femenino , Masculino , Microscopía Electrónica de Rastreo , Proyectos Piloto , ConejosRESUMEN
BACKGROUND/AIMS: Merkel cell carcinoma (MCC) is a rare malignant cutaneous neuroendocrine tumour that mostly affects the elderly. It shows rapid progression of the primary tumour, together with a vertical growth pattern into the underlying subcutaneous tissue. Metastatic dissemination to regional lymph nodes is early and frequent. Tenascin-C (Tn-C) is a large extracellular matrix glycoprotein that is expressed in various benign and malignant processes. Expression of Tn-C is also associated with invasion and cellular proliferation, and is often downregulated in fully evolved advanced carcinomas. In previous studies, Tn-C expression correlated with prognosis in tumours of different origin. METHODS: Immunohistochemistry was used to investigate the expression of Tn-C in 25 MCC specimens and to evaluate the prognostic importance of this glycoprotein. RESULTS: Seventeen samples expressed Tn-C. Staining was mainly seen in the invasion borders and within the connective tissue septae inside the tumours. The expression of Tn-C correlated significantly with large tumour size. There was also frequent expression of Tn-C in primary tumours with metastatic dissemination. Most of the Tn-C negative samples were of small size. CONCLUSIONS: Tn-C expression seems to increase with tumour size and malignant behaviour. Expression was slightly enhanced in tumours with high proliferative indices. Expression is seen mainly in areas of invasive growth and, in this respect, resembles that of other invasive tumours.