Mutation characteristics of osteosarcoma: a single center study of 64 cases using next-generation sequencing / 中华病理学杂志

Objective: To investigate the distribution and characteristics of gene mutations in osteosarcoma, and to analyze the frequency and types of detectable mutations, and to identify potential targets for individualized treatment of osteosarcoma. Methods: The fresh tissue or paraffin-embedded tissue samples of 64 cases of osteosarcoma that were surgically resected or biopsied and then subject to next generation sequencing, were collected from Beijing Jishuitan Hospital, China from November 2018 to December 2021. The tumor DNA was extracted to detect the somatic and germline mutations using targeted sequencing technology. Results: Among the 64 patients, 41 were males and 23 were females. The patient age ranged from 6 to 65 years with a median age of 17 years, including 36 children (under 18 years old) and 28 adults. There were 52 cases of conventional osteosarcoma, 3 cases of telangiectatic osteosarcoma, 7 cases of secondary osteosarcoma, and 2 cases of parosteosarcoma. The detection rate of gene mutations was overall 84.4% (54/64). There were 324 variations in 180 mutated genes, including 125 genes with copy number variations, 109 single nucleotide variants, 83 insertions or deletions, and 7 gene fusions. The most common mutated genes were TP53, VEGFA, CCND3, ATRX, MYC, RB1, PTEN, GLI1, CDK4 and PTPRD. Among them, TP53 had the highest mutation rate (21/64, 32.8%), single nucleotide variant was the main mutation type (14/23, 60.9%), and 2 cases carried the TP53 germline mutation. VEGFA and CCND3 showed copy number amplification simultaneously in 7 cases. Conclusions: The high-frequency mutation of TP53 suggests that it plays an important role in the pathogenesis and development of osteosarcoma. VEGFA, CCND3 and ATRX are mutated genes in osteosarcoma and worthy of further studies. Combination of pathologic diagnosis and next generation sequencing with clinical practice can guide individualized treatment for patients with refractory, recurrent and metastatic osteosarcoma.

Effects of miR-143 on the migration and invasion of osteosarcoma cells by regulating MMP-13 expression / 中国骨伤

OBJECTIVE@#To explore the effect of miR-143 regulating matrix metalloproteinase(MMP)-13 expression on migration and invasion of osteosarcoma cells.@*METHODS@#The mouse osteosarcoma cell line 143B cells were cultured in 96-well plates, and blank group, negative group, positive group, and intervention group were set up. Then, the blank group did no treatment 50 μg miR-143 mimic was added to positive group, negative group added equal mimic NC (control sequence of miR-143 mimic), the intervention group was added 50 μg miR-143 mimic and 10 μg MMP-13 protein, all groups continued to culture for 3 to 6 hours, and finally the serum was aspirated to treat for half an hour. The protein expressions of miR-143 and MMP-13 in each group were measured by fluorescence quantitative PCR experiment and Western blot experiment, respectively, and the invasion and migration abilities of cells were measured by Transwell and scratch experiments.@*RESULTS@#The expression of MMP-13 protein in the positive group and the intervention group was significantly lower than that in the blank group, and the positive group was lower than the intervention group (P<0.05);The mean numbers of invasive cells in blank group, negative group, positive group and intervention group were (1 000.01±44.77), (959.25±46.32), (245.04±4.33), (634.06±33.78) cells/field, respectively;the scratch healing rate of the positive group and the intervention group was significantly lower than that of the blank group, and the positive group was lower than the intervention group (P<0.05).@*CONCLUSION@#MMP-13 is a target of miR-143, which can reduce the migration and invasion ability of osteosarcoma cells by inhibiting the expression of MMP-13.

Long-term effectiveness of uncemented allograft-prosthesis composite for reconstruction of bone defects after proximal femur tumor resection / 中国修复重建外科杂志

OBJECTIVE@#To investigate the long-term effectiveness of uncemented allograft-prosthesis composite (APC) for reconstruction of bone defects after proximal femur tumor resection.@*METHODS@#Between June 2007 and March 2014, 21 patients who underwent uncemented APC reconstruction of proximal femur after tumor resection were retrospectively evaluated. There were 9 males and 12 females with an average age of 33.2 years (range, 19-54 years). There were 9 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 4 cases of osteoblastic osteosarcoma, 2 cases of chondrosarcoma, and 1 case of undifferentiated pleomorphic sarcoma. Thirteen cases of benign bone tumors were all classified as stage 3 by Enneking staging; and 8 cases of malignant bone tumors were classified as grade ⅡB in 7 cases and grade ⅡA in 1 case according to the American Joint Committee on Cancer (AJCC) staging system. Among them, 7 patients underwent reoperation after recurrence, and the rest were primary operations; 8 patients presented with pathological fractures. The preoperative Harris hip score (HHS) and American Musculoskeletal Tumor Society (MSTS) score was 40 (30, 49) and 9.1±3.5, respectively. The length of osteotomy was 80-154 mm, with an average of 110 mm. At 1 year after operation and last follow-up, HHS and MSTS scores were utilized to evaluate the function of hip joint; the gluteus medius strength score was used to evaluation of the hip abduction function. Image examinations were taken at 1, 3, 6, 9, and 12 months after operation and every year thereafter to assess the union of allograft-host bone interfaces. Intra- and post-operative complications were also recorded.@*RESULTS@#All patients were followed up 84-163 months (mean, 123.5 months). At 1 year after operation and last follow-up, the HHS and MSTS scores significantly improved when compared with the preoperative scores ( P<0.05). However, there was no significant difference in the HHS score, MSTS score, and gluteus medius strength score between the two time points after operation ( P>0.05). Image examination showed that all allograft-host bone interfaces achieved union after 5-10 months (mean, 7.6 months). At last follow-up, all patients had bone resorption, including 11 severe cases, 4 moderate cases, and 6 mild cases; the bone resorption sites included Gruen 1, 2, and 7 regions. Complications included 10 fractures and 1 prosthetic fracture. Local recurrence occurred in 3 patients and pulmonary metastasis in 3 patients.@*CONCLUSION@#Uncemented APC is a reliable method for the reconstruction of bone defects after proximal femur tumor resection. It has the good long-term effectiveness and possesses obvious advantages in the union at the bone-bone surface.

Bioinformatics analysis of differently expressed genes in osteoblastic sarcoma and screening of key genes / 中华肿瘤杂志

Objective: To screen the different expressed genes between osteosarcoma and normal osteoblasts, and find the key genes for the occurrence and development of osteosarcoma. Methods: The gene expression dataset GSE33382 of normal osteoblasts and osteosarcoma was obtained from Gene Expression Omnibus (GEO) database. The different expressed genes between normal osteoblasts and osteosarcoma were screened by limma package of R language, and the different expressed genes were analyzed by Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The protein interaction network was constructed by the String database, and the network modules in the interaction network were screened by the molecular complex detection (MCODE) plug-in of Cytoscape software. The different expressed genes contained in the first three main modules screened by MCODE were analyzed by gene ontology (GO) using the BiNGO module of Cytoscape software. The MCC algorithm was used to screen the top 10 key genes in the protein interaction network. The gene expression and survival dataset GSE39055 of osteosarcoma was obtained from GEO database, and the survival analysis was performed by Kaplan-Meier method. The data of 48 patients with osteosarcoma treated in the First Affiliated Hospital of Fujian Medical University from January 2005 to December 2015 were selected for verification. The expression of STC2 protein in osteosarcoma was detected by immunohistochemical method, and the survival analysis was carried out combined with the clinical data of the patients. Results: A total of 874 different expressed genes were identified from GSE33382 dataset, including 402 down-regulated genes and 472 up-regulated genes. KEGG enrichment analysis showed that different expressed genes were mainly related to p53 signal pathway, glutathione metabolism, extracellular matrix receptor interaction, cell adhesion molecules, folate tolerance, and cell senescence. The top 10 key genes in the interaction network were GAS6, IL6, RCN1, MXRA8, STC2, EVA1A, PNPLA2, CYR61, SPARCL1 and FSTL3. STC2 was related to the survival rate of patients with osteosarcoma (P<0.05). The results showed that the expression of STC2 protein was related to tumor size and Enneking stage in 48 cases of osteosarcoma. The median survival time of 25 cases with STC2 high expression was 21.4 months, and that of 23 cases with STC2 low expression was 65.4 months. The survival rate of patients with high expression of STC2 was lower than that of patients with low expression of STC2 (P<0.05). Conclusions: Bioinformatics analysis can effectively screen the different expressed genes between osteosarcoma and normal osteoblasts. STC2 is one of the important predictors for the prognosis of osteosarcoma.

Down-regulation of HCP5 inhibits cell proliferation, migration, and invasion through regulating EPHA7 by competitively binding miR-101 in osteosarcoma

Patients with osteosarcoma (OS) usually have poor overall survival because of frequent metastasis. Long non-coding RNAs (lncRNAs) have been reported to be associated with tumorigenesis and metastasis. In this study, we investigated the expression and roles of lncRNA human histocompatibility leukocyte antigen (HLA) complex P5 (HCP5) in OS, aiming to provide a novel molecular mechanism for OS. HCP5 was up-regulated both in OS tissues and cell lines and high expression of HCP5 was associated to low survival in OS patients. Down-regulation of HCP5 inhibited cell proliferation, migration, and invasion, suggesting its carcinogenic role in OS. miR-101 was targeted by HCP5 and its expression was decreased in OS. The inhibitor of miR-101 reversed the impact of HCP5 down-regulation on cell proliferation, apoptosis, and metastasis in OS. Ephrin receptor 7 (EPHA7) was proved to be a target of miR-101 and had ability to recover the effects of miR-101 inhibitor in OS. In conclusion, lncRNA HCP5 knockdown suppressed cell proliferation, migration, and invasion, and induced apoptosis through depleting the expression of EPHA7 by binding to miR-101, providing a potential therapeutic strategy of HCP5 in OS.

O Cripto-1 é um potencial biomarcador para o diagnóstico diferencial dos tumores ósseos benignos e malignos dos maxilares / Cripto-1 is a potential biomarker for the differential diagnosis of benign and malignant jaw bone tumors

O termo lesão fibro-óssea dos maxilares (LFOM) é uma designação inespecífica para um grupo de distúrbios caracterizados, morfologicamente, pela substituição do tecido ósseo por uma matriz de tecido conjuntivo fibrosa, a qual exibe neoformação de tecido ósseo com diferentes graus de mineralização. O diagnóstico preciso das LFOM não é fácil e só pode ser realizado após uma análise minuciosa dos aspectos clínicos, radiológicos e histológicos. No entanto, deve-se admitir que alguns casos desafiam a exatidão na emissão do diagnóstico. Considerando a diversidade do comportamento biológico das lesões e as pesquisas sobre a identificação de potenciais marcadores moleculares, o objetivo deste trabalho foi realizar uma análise imunohistoquímica do cripto-1 (CR-1) e da ß-catenina em uma série de casos diagnosticados microscopicamente como displasia fibrosa (DF) (n=30), fibroma ossificante central (FOC) (n=28) e osteossarcoma (OS) (n=5) armazenados nos arquivos do Serviço de Anatomia Patológica Oral de uma população brasileira. As expressões imuno-histoquímicas foram analisadas através de escore imunorreativo. Os dados obtidos foram inseridos em um arquivo do software Microsoft Excel® e, posteriormente, analisados no software Statistical Package for Social Science. Para todos os testes estatísticos utilizados, o nível de significância foi estabelecido em 5% (p<0,05). O CR-1 exibiu predominância de um padrão fortemente positivo para os casos de FOC e OS, e do padrão moderado para os casos de DF (p<0,001). A ß-catenina exibiu predominância do padrão negativo para os casos de FOC e DF, e do padrão fortemente positivo para os casos de OS (p=0,001). O teste de correlação de Spearman revelou correlação positiva entre os escores imunorreativos de CR-1 e ß-catenina. Os resultados desta pesquisa sugerem a participação do CR-1 na patogênese do FOC e OS, assim como o uso dessa proteína como potencial biomarcador molecular para o diagnóstico diferencial de LFOM (AU).

Fibro-osseous lesions of maxilar (FOLM) is a non-specific designation for a group of disorders characterized, morphologically, by replacement of bone tissue by a matrix of fibrous connective tissue, showing neoformation of bone tissue with varying degrees of mineralization. Precise diagnosis of FOLM is not easy, and requires careful analyisis of clinical, radiological and histological aspects. Even so, some cases still challenge accuracy in diagnosis. Considering the diversity of biological behaviour of the lesions and the research regarding identification of potential molecular markers, this study aims to perform immunohistochemical analysis of crypto-1 and ß-catenin in a series of cases diagnosed microscopically as fibrous dysplasia (FD) (n=30), central ossifying fibroma (COF) (n=28) and osteossarcoma (OS) (n=5), stored in archives of Oral Pathological Anatomy Service of a Brazilian population. Immunohistochemical expressions were analysed by imunorreactive score. All data obtained was inserted into a file of Microsoft Excel® software (Microsoft Corporation, USA) and then transferred to a database of SPSS® for Windows software (Statistical Package for Social Sciences; IBM, USA), version 20.0. For all statistical tests used, the significance level established was p ≤ 0.05. CR-1 showed a predominant pattern of strong positive in COF and OS cases, and a moderate positive in FD cases (p<0,001). ß-catenin showed a predominant negative pattern for COF and FD cases, and a predominant strong positive pattern for OS cases (p=0,001). Spearman correlation tests showed positive correlation of the imunoreative scores of CR-1 and ß-catenin. Those results suggests CR-1 could be involved in the pathogenesis of COF and OS, and this protein could be used as a potential molecular biomarker for diferential diagnosis of FOLM (AU).

Lung metastases at the initial diagnosis of high-grade osteosarcoma: prevalence, risk factors and prognostic factors. A large population-based cohort study

ABSTRACT BACKGROUND: Osteosarcoma is the most prevalent malignant bone tumor in children and adolescents. Lung metastases are associated with poor prognosis. OBJECTIVE: The aim here was to explore the prevalence of and risk and prognostic factors for lung metastases in high-grade osteosarcoma patients. DESIGN AND SETTING: Retrospective cohort study based on the Surveillance, Epidemiology and End Results (SEER) database in the United States. METHODS: Data on 1,408 high-grade osteosarcoma patients registered in the SEER database between 2010 and 2015 were extracted. From these, all patients with high-grade osteosarcoma and initial lung metastasis were selected for analysis on risk and prognostic factors for lung metastases. Overall survival was estimated. RESULTS: There were 238 patients (16.90%) with lung metastases at diagnosis. Axial location, tumor size > 10 cm (odds ratio, OR 3.19; 95% confidence interval, CI: 1.58-6.45), higher N stage (OR 4.84; 95% CI: 1.94-12.13) and presence of bone metastases (OR 8.73; 95% CI: 4.37-17.48) or brain metastases (OR 25.63; 95% CI: 1.55-422.86) were significantly associated with lung metastases. Younger age and surgical treatment (hazard ratio, HR 0.46; 95% CI: 0.30-0.71) favored survival. Median survival was prolonged through primary tumor surgery. CONCLUSIONS: The factors revealed here may guide lung metastasis screening and prophylactic treatment for osteosarcoma patients. A primary tumor in an axial location, greater primary tumor size, higher lymph node stage and presence of bone or brain metastases were significantly correlated with lung metastases. The elderly group (≥ 60 years) showed significant correlation with poor overall survival. For improved survival among high-grade osteosarcoma patients with lung metastases, aggressive surgery on the primary tumor site should be encouraged.

Expressão de neurotrofinas e de seus receptores no osteossarcoma primário / Expression of neurotrophins and their receptors in primary osteosarcoma

RESUMO Objetivo: determinar a expressão de neurotrofinas e seus receptores tirosina quinases em pacientes com osteossarcoma (OS) e sua correlação com desfechos clínicos. Métodos: biópsias de tumores primários de pacientes com OS tratados em uma única instituição, consecutivamente, entre 2002 e 2015, foram analisados através de imuno-histoquímica para expressão de receptores de tirosina quinase A e B (TrKA e TrKB), fator de crescimento neural (NGF) e fator neurotrófico derivado do cérebro (BDNF). De forma independente, dois patologistas classificaram os marcadores de imuno-histoquímica como negativos (negativos e focais fracos) ou positivos (moderado focal/difuso ou forte focal/difuso). Resultados: foram analisados dados de 19 pacientes (10 do sexo feminino e 9 do masculino) com mediana de idade de 12 anos (5 a 17,3 anos). Dos tumores, 83,3% estavam localizados em membros inferiores e 63,2% dos pacientes eram metastáticos ao diagnóstico. A sobrevida global em cinco anos foi de 55,3%. BDNF foi positivo em 16 pacientes (84%) e NGF em 14 pacientes (73%). TrKA e TrKB apresentaram coloração positiva em quatro (21,1%) e oito (42,1%) pacientes, respectivamente. A análise de sobrevida não demonstrou diferença significativa entre receptores TrK e neurotrofinas. Conclusão: amostras de OS primário expressam neurotrofinas e receptores TrK através de imuno-histoquímica. Estudos futuros podem auxiliar na identificação do papel das mesmas na patogênese do OS e determinar se há possível correlação prognóstica.

ABSTRACT Objective: to determine the expression of neurotrophins and their tyrosine-kinase receptors in patients with osteosarcoma (OS) and their correlation with clinical outcomes. Methods: we applied immunohistochemistry to biopsy specimens of patients consecutively treated for primary OS at a single institution between 2002 and 2015, analyzing them for expression receptors of tyrosine kinase A and B (TrKA and TrKB), neural growth factor (NGF) and brain derived neurotrophic factor (BDNF). Independently, two pathologists classified the immunohistochemical markers as negative (negative or weak focal) or positive (moderate focal/diffuse or strong focal/diffuse). Results: we analyzed data from 19 patients (10 females and 9 males), with median age of 12 years (5 to 17.3). Tumors' location were 83.3% in the lower limbs, and 63.2% of patients had metastases at diagnosis. Five-year overall survival was 55.3%. BDNF was positive in 16 patients (84%) and NGF in 14 (73%). TrKA and TrKB presented positive staining in four (21,1%) and eight (42,1%) patients, respectively. Survival analysis showed no significant difference between TrK receptors and neurotrophins. Conclusion: primary OS samples express neurotrophins and TrK receptors by immunohistochemistry. Future studies should explore their role in OS pathogenesis and determine their prognostic significance in larger cohorts.

Osteosarcoma of the jaw - experience at the Medical University Vienna and comparative study with international tumor registries

OBJECTIVES: Osteosarcoma of the jaw (OSAJ) is fundamentally different in clinical practice from its peripheral counterparts. Studies are difficult to conduct due to low incidence rates. The primary aim of this study was to provide for the first time a comprehensive retrospective analysis of the treatment concepts and outcome data of OSAJ patients treated at the University Hospital Vienna and to compare these with two recently published studies on OSAJ. The clinical study was accompanied by a biomarker study investigating the prognostic relevance of melanoma-associated antigen-A (MAGE-A) in OSAJ specimens. METHOD: Eighteen patients were included, and their outcomes were compared to published data. Immunohistochemistry was performed with mouse monoclonal antibodies against MAGE-A. Survival rates were estimated by the Kaplan-Meyer method. The log-rank test was used to analyze potential prognostic parameters. Fisher's exact test was performed to define the significant differences between the survival rates of the current study and the DOESAK registry. RESULTS: Disease-specific survival was 93.8% after five and 56.3% after ten years. The development of metastases (p=0.033) or relapse (p=0.037) was associated with worsened outcomes in our group as well as in the comparative group. Despite the different treatment concepts of the study groups, survival rates were comparable. MAGE-A failed to show prognostic relevance for OSAJ patients. CONCLUSIONS: Uncertainties about the optimal treatment strategies of OSAJ patients will currently remain. Thus, prospective studies of OSAJ are needed but are only feasible in a multicenter study setting, conducted over a prolonged time period.

Metástases pulmonares em crianças: estamos operando desnecessariamente? / Pulmonary metastases in children: are we operating unnecessarily?

RESUMO Objetivo: determinar, em pacientes pediátricos portadores de neoplasias malignas, as características de nódulos pulmonares identificados à tomografia computadorizada, capazes de diferenciar nódulos benignos de metástases. Métodos: estudo retrospectivo de pacientes submetidos a ressecções pulmonares de nódulos diagnosticados como metástases em um período de sete anos. Achados de tomografia e da cirurgia, assim como resultados dos exames anatomopatológicos foram comparados. Resultados: nove pacientes, submetidos a 11 intervenções cirúrgicas, foram estudados. Entre as variáveis estudadas, apenas o tamanho do nódulo, maior do que 12,5mm provou ser estatisticamente significante para predizer malignidade. Conclusão: esse estudo sugere que, entre as características tomográficas de nódulos pulmonares de crianças portadoras de neoplasias malignas, apenas o tamanho da lesão foi preditor de malignidade.

ABSTRACT Objective: to determine, in pediatric patients with malignant neoplasms, the characteristics of pulmonary nodules identified on computed tomography, as well as the possibility of differentiating benign lesions from metastases. Methods: we conducted a retrospective study of patients submitted to pulmonary resections of nodules diagnosed as metastases in a period of seven years. We compared computed tomography and surgery findings, as well as results of anatomopathological examinations. Results: we studied nine patients submitted to 11 surgical interventions. Among the studied variables, only nodule size greater than 12.5mm proved to be statistically significant to predict malignancy. Conclusion: among the tomographic characteristics of pulmonary nodules in children with malignant neoplasms, only the size of the lesion was a predictor of malignancy.

Chondroblastic osteosarcoma mimicking periapical abscess

Abstract Lesions of non-endodontic origin may mimic periapical abscess. Osteosarcoma is a rare malignant lesion. Case report The present report describes a case of chondroblastic osteosarcoma in the periapical region of teeth #29, #30, and #31 of an 18-year-old male. Clinical history showed self-reported discomfort in the right posterior gingiva for over a month. Physical examination showed a small expansion and redness of the right mandibular buccal and lingual cortical plates, but no signs of pain or inflammation were observed. All the teeth responded positively to pulp sensibility. Periapical and panoramic radiographs showed slight periapical radiolucency in the roots of teeth #29 and #30, clear periodontal ligament space widening, and evident loss of lamina dura. Incisional biopsy was performed, and based on microscopic findings the diagnosis of chondroblastic osteosarcoma was confirmed. Conclusions Non-endodontic diseases associated with tooth root apex, such as chondroblastic osteosarcoma, should be included in differential diagnosis of jaw lesions that resemble periapical abscess.

Tumor Phyllodes con transformación a osteosarcoma / Breast osteosarcoma originating in a phyllodes tumor: report of one case

Phyllodes tumors account for less than 1% of tumors of the mammary gland, have both epithelial and stromal components and are classified as benign, borderline and malignant. The malignant tumors are highly heterogeneous: they can differentiate to liposarcomas, fibrosarcomas, rhabdomyosarcomas, chondrosarcomas or osteosarcomas. The differentiation to osteosarcoma is extremely rare, constitutes 1.3% of cases and is very aggressive. The standard treatment of these tumors is surgical. The role of radiotherapy and chemotherapy is not clear. However, in patients in whom wide surgical margins are not achieved, adjuvant radiotherapy can be of help. We report a 63 years old female with a right breast osteosarcoma with an osteoclastic component, originating in a phyllodes tumor. The tumor was excised surgically and afterwards she was treated with 10 sessions of 50 Gy of radiotherapy in 25 fractions. She has remained free of disease for the last 10 months.

Osteosarcoma telangiectásico en un lactante / Telangiectatic osteosarcoma in an infant

Resumen: Introducción: El osteosarcoma es uno de los tipos de cáncer más común en la etapa escolar y en la adolescencia, y es el más común de los tumores óseos malignos en este grupo de edad. Frecuentemente, el osteosarcoma es hallado en los huesos largos de las extremidades. Existen muy pocos casos descritos en menores de 5 años. Hasta donde se sabe, no hay ningún caso reportado en lactantes. La variedad telangiectásica es poco común y no existen casos reportados antes de la edad preescolar. Caso clínico: Se presenta el caso clínico de una paciente lactante de 10 meses de edad que presentó un tumor lítico en la novena costilla derecha, que posterior a la resección fue clasificado como osteosarcoma telangiectásico. Conclusiones: El osteosarcoma telangiectásico en la edad pediátrica es poco común. A la fecha, la paciente ha presentado buena respuesta al tratamiento, aunque se desconoce el pronóstico y la supervivencia de este padecimiento.

Abstract: Background: Osteosarcoma is one of the most common types of cancer in childhood and adolescence and it is the most common malignant bone tumor in this group of age. Osteosarcoma is frequently found in long bones of the extremities. There are very few cases described in children under 5 years of age, and according to this review, none in infants. The telangiectatic variant is uncommon, and there are no reported cases before preschool age. Case report: A 10-month-old female infant with a lithic tumor of the ninth right rib, which was classified after resection as a telangiectatic osteosarcoma, is presented. Conclusions: Telangiectatic osteosarcoma in the pediatric age is very uncommon. To date, the patient has presented good response to treatment, although the prognosis and survival of this condition is unknown.

Knockdown of ubiquitin-specific peptidase 39 inhibited the growth of osteosarcoma cells and induced apoptosis in vitro

BACKGROUND: Ubiquitin specific peptidase 39 (USP39), an essential factor in the assembly of the mature spliceosome complex, has an aberrant expression in several cancer. However, its function and the corresponding mechanism on human osteosarcoma has not been fully explored yet. METHODS: The mRNA and DNA copies of USP39 were increased in osteosarcoma cancer tissues compared with the one in human normal tissues according to datasets from the publicly available Oncomine database. A further western blot analysis also demonstrated an aberrant endogenous expression of USP39 in three different osteosarcoma cells. Then lentivirus-mediated short hairpin RNA (shRNA) was designed to silence USP39 in human osteosarcoma cell line U2OS, which is used to test the impact of USP39-silencing on cellular proliferation, colony formation, cell cycle distribution and apoptosis. RESULTS: Knockdown of USP39 expression in U2OS cell significantly decreased cell proliferation, impaired colony formation ability. A further analysis indicated suppression of USP39 arrested cell cycle progression at G2/M phase via p21 dependent way. In addition, the results of Annexin V/7-AAD staining suggested the knockdown of USP39 could promote U2OS cell apoptosis through PARP cleavage. CONCLUSIONS: These results uncover the critical role of USP39 in regulating cancer cell mitosis and indicate USP39 is critical for osteosarcoma tumorigenesis.

Osteosarcoma parostal de bajo grado: Evolución oncológica y clínica / Low grade parosteal osteosaroma. Clinical and oncological outcomes]

El objetivo de este estudio fue analizar una serie de pacientes con osteosarcoma parostal de bajo grado y los resultados de su tratamiento quirúrgico y reconstrucción con un trasplante óseo. Se realizó una búsqueda retrospectiva en nuestra base de datos oncológica entre 1980 y 2010 de todos los pacientes con diagnóstico de osteosarcoma parostal. Se incluyeron para el análisis únicamente los osteosarcomas parostales de bajo grado, tratados quirúrgicamente con cirugía de conservación de miembro y reconstruidos con trasplante óseo cadavérico fresco congelado. Se incluyeron 22 pacientes en el estudio. La edad media de la serie fue de 32 ± 11 años (10-59) y el seguimiento medio de 93 ± 69 meses (8-237). La supervivencia global de los pacientes analizados fue de 91% (IC95%: 79-100) a 10 años. Cuatro pacientes (18%) presentaron una recidiva local de la enfermedad, dos de éstas fueron clasificadas histológicamente como osteosarcoma parostal desdiferenciado. Dos pacientes desarrollaron enfermedad a distancia, siendo el pulmón el único sitio de localización. La tasa de supervivencia de las reconstrucciones de la cirugía de conservación de miembro a 10 años fue de 65% (IC95%: 44-86). La supervivencia a largo plazo de los pacientes con osteosarcoma parostal de bajo grado es superior al 90%. La resección quirúrgica con márgenes amplios debe ser el tratamiento de elección y la reconstrucción biológica es una alternativa válida.

The objective of the study was to analyze a group of patients with low grade parosteal osteosarcoma treated with limb salvage surgery and reconstructed with bone allograft. A retrospective review from our oncologic data base between 1980 and 2010 was done and all patients with diagnosis of low grade parosteal osteosarcoma, treated with limb salvage surgery and reconstructed with allograft were included. Twenty-two patients were included for the analysis. The mean age was 32 ± 11 years (10-59) y the mean follow-up 93 ± 69 months (8-237). Ten year overall survival of the series was 91% (95%CI: 79-100). Four patients developed local recurrence, 2 of them histological classified after the resection dedifferentiated parosteal osteosarcoma. Two patients developed distant recurrence, being the lung the only site of metastasis. Ten year limb salvage reconstruction survival was 65% (95%CI: 44-86). Long term survival rate in low grade parosteal osteosarcoma is over 90%. Surgical resection wide margin should be the elective treatment and biological limb salvage reconstruction is a good alternative.

Unusual Malignant Solid Neoplasms of the Kidney: Cross-Sectional Imaging Findings

Malignant kidney neoplasms are the most frequently encountered solid kidney masses. Although renal cell carcinoma is the major renal malignancy, other solid malignant renal masses should be considered in the differential diagnosis of solid renal masses that do not contain a macroscopic fatty component. In this pictorial essay, we present the imaging findings of a primitive neuroectodermal tumor, primary liposarcoma of the kidney, primary neuroendocrine tumor, leiomyosarcoma, synovial sarcoma, malignant fibrous histiocytoma, sclerosing fibrosarcoma and renal metastasis of osteosarcoma.

Triptolide induces apoptosis through extrinsic and intrinsic pathways in human osteosarcoma U2OS cells.

Triptolide, a diterpene derived from Tripterygium wilfordii Hook f., a Chinese medicinal herb, has been reported to inhibit cell proliferation and induce apoptosis in various human cancer cells, but its anticancer effects on human osteosarcoma cells have not yet been elucidated. In this study, we investigated whether triptolide induces apoptosis in human osteosarcoma cells and the underlying molecular mechanisms. We firstly demonstrated that triptolide inhibited cell growth and induced apoptosis in U2OS cells. Western blot analysis showed that the levels of procaspase-8, -9, Bcl-2, Bid and mitochondrial cytochrome c were downregulated in triptolide-treated U2OS cells, whereas the levels of Fas, FasL, Bax, cytosolic cytochrome c, cleaved caspase-3 and cleaved PARP were upregulated. These results suggest that triptolide induces apoptosis in U2OS cells by activating both death receptor and mitochondrial apoptotic pathways.

Effects of fibronectin and type IV collagen on osteosarcoma cell apoptosis.

The aims of this study are the investigation of the effects of fibronectin and type IV collagen extracellular matrix proteins and the role of caspase-3 and -9 on cis-platin induced U2-OS apoptosis were studied. First the cytotoxic effects of cis-platin on cell system were investigated by colorimetric method and than morphological and ELISA analysis were used for determination of cell apoptosis when induced with cis-platin. In addition, after adhering the cells to fibronection or type IV collagen proteins, the apoptotic rate and the effects of caspase-3 and -9 were also investigated by ELISA in presence of specific inhibitors. U2-OS cells showed 20% cytotoxicity after treatment with 2.4 µM of cis-platin for 48 h. Morphological and the numerical data showed that cis-platin was able to induced apoptosis on cells as a dose-dependent manner. Caspase-3 and -9 inhibitors inhibited cis-platin-induced apoptosis in U2-OS cells, respectively. The binding of cells to 10 µg/mL of fibronectin but not type IV collagen enhanced the apoptosis about 2.5 fold that effects inhibited with caspase-3 inhibitor. The caspase-3 and -9 are involved in the apoptotic signals induced by cis-platin in U2-OS. The binding to fibronectin, but not type IV collagen enhanced the apoptotic response of U2-OS and fibronectin-dependent apoptosis was activated by caspase-3. These finding might be useful for patients to fight against osteosarcoma.

Imaging review of 250 cases of primary osteogenic sarcoma and other subtypes: our experience at king hussein medical center and hussein cancer center

Radiology plays a crucial role in diagnosis, work-up and staging of osteosarcoma. The main aim of the study is to review, analyze and characterize the imaging findings of a large series of histologically proven osteosarcomas focusing on the nonconventional subtypes. We retrospectively reviewed the imaging findings of 250 cases with histologically proven primary osteosarcoma. The study was conducted at King Hussein Medical Center and King Hussein Cancer Center, Amman-Jordan during the period 2003-2012. Approval by the ethical committee and institutional review board was taken from both institutions before starting the study. Patient demographic data was recorded. Images from plain radiographs [n=238], angiograms [n=28], bone isotope scans [n=56], computed tomography scans [n=99], computed tomography angiograms [n=27] and magnetic resonance imaging [n=189] were evaluated for the origin site, location, tumor size, matrix pattern, extrinsic and intrinsic characteristics and the soft tissue component of the tumor. The sample included 162 males [65%] and 88 females [35%], with an age range of 12-48 years [mean age of 23.5 years]. Simple descriptive statistical methods [frequency, mean and percentage] were used to describe the study variables. The most common histological diagnoses were conventional [n=193], telangiectatic [n=14], small cell [n=3], low grade central [n=3], high grade surface [n=2], parosteal [n=4], and periosteal [n=5] and non specific [n= 26]. The most frequent origin site in the long bones is the metaphysis [80%] followed by diaphysis [9%], and less frequently the epiphysis [2%], 10% were found in the spine and flat bones. The commonest lesion location was distal femur [25%], proximal femur [18%], proximal humerus [17%], proximal tibia [15%], spine and flat bones [16%], other places [9%]. The tumor size ranged from 2-21cm. The majority of cases [78%] demonstrated osteoid matrix abnormal mineralization, 32 of them showed obvious and marked mineralization, three cases with marked mineralization were noted in the spine, one of them gave an ivory vertebra appearance. A purely lytic pattern was seen in 48%. Soft-tissue components were seen in 58% of cases. This study provides a good relation between the radiological imaging and histological subtypes of osteosarcoma in a relatively large series of osteosarcoma and highlights our experience at King Hussein Medical and Cancer Centers.

Osteosarcoma condroblástico gigante del fémur: reporte de un caso / Giant chondroblastic osteosarcoma of the femur: a case report

El osteosarcoma es un tumor maligno compuesto de células fusiformes, que se caracteriza por la producción de tejido osteoide y hueso, su crecimiento es rápido con extensión locoregional y difusión metastásica a pulmón. Generalmente 20% de los pacientes presentan metástasis en el momento del diagnóstico. Se observa con frecuencia en los huesos largos de los adolescentes y adultos jóvenes con mayor afectación del sexo masculino. El tratamiento de los pacientes con osteosarcomas se basa en la resección amplia y completa o en una amputación del tumor primario, y en la administración de quimioterapia coadyuvante. Presentamos el caso de paciente masculino de 21 años, quien consultó por una tumoración en la rodilla izquierda de rápido crecimiento hasta alcanzar 80 cms de perímetro. La biopsia incisional reportó un condrosarcoma condroblástico. En vista de no tener respuesta al tratamiento coadyuvante, se decidió realizar una desarticulación coxofemoral. Cuando el osteosarcoma es resistente a la quimioterapia y su crecimiento continúa, se deben realizar procedimientos radicales para garantizar la sobrevida del paciente(AU)

Osteosarcoma is a malignant tumor composed of spindle cells, characterized by the production of osteoid tissue and bone is growing rapidly, with locoregional extension and metastatic spread to the lung. Generally 20% of patients have metastases at diagnosis. It most often occurs in the long bones of adolescents and young adults with greater male involvement. Treating osteosarcoma patients is based on wide and complete resection or amputation of the primary tumor and the administration of adjuvant chemotherapy. We present the case of male patient 21, who presented a tumor in his left knee rapidly growing up to 80 cm in circumference. Incisional biopsy chondroblastic reported chondrosarcoma. In view of having no adjuvant treatment response was decided to hip disarticulation. When osteosarcoma is resistant to chemotherapy and growth continues, radical procedures must be performed to ensure the survival of the patient(AU)