Histopatología del osteosarcoma

El diagnóstico del osteosarcoma plantea una serie de problemas específicos. De hecho, se debe tener en cuenta la existencia de diversas variantes, con pronósticos diferentes y que requieren enfoques terapéuticos igualmente distintos. En este mismo sentido, la introducción de nuevos protocolos terapéuticos, incluyendo la quimioterapia preoperatoria, requiere una evaluación histopatológica cuidadosa del especimen a fin de cuantificar la necrosis inducida por la quimioterapia y los márgenes quirúrgicos. El presente estudio analiza las diferentes variantes histopatológicas y los problemas que se relacionan con la evaluación de los efectos de la quimioterapia preoperatoria sobre el especimen resecado.Diagnosis of osteosarcoma presents specific problems. In fact, several and different varieties, presenting different prognosis and requiring different treatments, have to be recognized. Moreover, the adoption of new therapeutic protocols including preoperative chemotherapy, requires a careful histopathological evaluation of the specimen to quantify the chemotherapy-induced necrosis and the surgical margins. This paper analyzes the different histopathological varieties and problems related to the evaluation of the effects on the resected specimen of preoperative chemotherapy

Imaging of hibernomas: A retrospective study on twelve cases

<p>Abstract</p> <p>Background</p> <p>To analyze the imaging features of hibernomas on computed tomography (CT) and magnetic resonance (MRI).</p> <p>Methods</p> <p>Twelve hibernomas were retrospectively assessed with CT and MR imaging and compared to the histology of the specimen</p> <p>Results</p> <p>Nine females and three males with a mean age of 30 years were included. Ten tumors occurred in the thigh and two affected the subcutis of the periscapular and buttock regions. On eight CT scans, seven (87,5%) lesions were homogeneous and mildly to moderately hyperdense compared to subcutaneous fat while one lesion was heterogeneous with mixed hypo and hyperattenuating areas. On six T1W images, five (83,3%) lesions appeared homogeneous and hypointense relative to subcutaneous fat and one was heterogeneous. Incomplete fat suppression was depicted in all cases. All lesions displayed marked enhancement. Large intratumoral vessels were depicted in three of the 12 (25%) cases. Septations were depicted on four of the eight unenhanced CT and on all six MRI examinations.</p> <p>Conclusions</p> <p>Hibernoma usually appears hypodense and hypointense relative to subcutaneous fat on pre-contrast CT and MR T1W with variable enhancement patterns and incomplete fat suppression on STIR or fat-saturated sequences. These characteristics relate directly to the presence of brown fat. However, atypical findings such as heterogeneous patterns of mixed fatty and non fatty components on unenhanced CT and MR T1W can be also encountered. Absence of large intratumoral vessels should not exclude hibernomas from the differential diagnosis of regional lipomatous tumors.</p

High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of Tumour Patients

Background. Unlike in most adult-onset cancers, an association between typical paediatric neoplasms and inflammatory triggers is rare. We studied whether immune system-related genes are activated and have prognostic significance in Ewing's sarcoma family of tumors (ESFTs). Method. Data analysis was performed on gene expression profiles of 44 ESFT patients, 11 ESFT cell lines, and 18 normal skeletal muscle samples. Differential expression of 238 inflammation and 299 macrophage-related genes was analysed by t-test, and survival analysis was performed according to gene expression. Results. Inflammatory genes are activated in ESFT patient samples, as 38 of 238 (16%) inflammatory genes were upregulated (P < 0.001) when compared to cell lines. This inflammatory gene activation was characterized by significant enrichment of macrophage-related gene expression with 58 of 299 (19%) of genes upregulated (P < 0.001). High expression of complement component 5 (C5) correlated with better event-free (P = 0.01) and overall survival (P = 0.004) in a dose-dependent manner. C5 and its receptor C5aR1 expression was verified at protein level by immunohistochemistry on an independent ESFT tumour tissue microarray. Conclusion. Immune system-related gene activation is observed in ESFT patient samples, and prognostically significant inflammatory genes (C5, JAK1, and IL8) for ESFT were identified

Metformin as an adjuvant drug against pediatric sarcomas: hypoxia limits therapeutic effects of the drug.

Metformin, a well-known insulin-sensitizer commonly used for type 2 diabetes therapy, has recently emerged as potentially very attractive drug also in oncology. It is cheap, it is relatively safe and many reports have indicated effects in cancer prevention and therapy. These desirable features are particularly interesting for pediatric sarcomas, a group of rare tumors that have been shown to be dependent on IGF and insulin system for pathogenesis and progression. Metformin exerts anti-mitogenic activity in several cancer histotypes through several molecular mechanisms. In this paper, we analyzed its effects against osteosarcoma, Ewing sarcoma and rhabdomyosarcoma, the three most common pediatric sarcomas. Despite in vitro metformin gave remarkable antiproliferative and chemosensitizing effects both in sensitive and chemoresistant cells, its efficacy was not confirmed against Ewing sarcoma xenografts neither as single agent nor in combination with vincristine. This discrepancy between in vitro and in vivo effects may be due to hypoxia, a common feature of solid tumors. We provide evidences that in hypoxia conditions metformin was not able to activate AMPK and inhibit mTOR signaling, which likely prevents the inhibitory effects of metformin on tumor growth. Thus, although metformin may be considered a useful complement of conventional chemotherapy in normoxia, its therapeutic value in highly hypoxic tumors may be more limited. The impact of hypoxia should be considered when novel therapies are planned for pediatric sarcomas

Prognostic and predictive role of CXCR4, IGF-1R and Ezrin expression in localized synovial sarcoma: is chemotaxis important to tumor response?

BACKGROUND: Synovial sarcoma (SS) is a rare tumor, with dismal survival when metastatic. The role of adjuvant chemotherapy is debated. New prognostic and predictive factors are needed. METHODS: We reviewed patients with localized SS; SS18-SSX fusion transcript presence was confirmed by FISH and RT-PCR. Expression of CXCR4, IGF-1R and Ezrin were evaluated by immunohistochemistry. RESULTS: Tumor samples from 88 SS patients (45 female; 43 male) with median age 37 years (range 11-63) were selected. The size of the lesion was\u2009&gt;\u20095 cm in 68% of patients and 34% of cases presented biphasic histotype. All patients underwent surgery, 56% adjuvant radiotherapy (RT), 65% adjuvant chemotherapy. A positive stain for IGF-1R was detected in 55 patients, with nucleus expression in 21 patients. CXCR4 was expressed in 74 patients, nuclear pattern in 31 patients. 80 SS were positive to Ezrin, 48 had cytoplasmatic location, 32 membrane location. With a median follow-up of 6 years (1-30 years), the 5-year overall survival (OS) was 70% (95% CI 60-81). 5-year OS was 63% (95% CI 41-85%) for patients with positive IGF-1R/nuclear expression, and 73% (95% CI 61-85%; P\u2009=\u20090.05) in negative patients. 5-year OS was 47% (95% CI 27-66%) in patients with positive CXCR4/nuclear staining, and 86% (95% CI 76-96%, P = 0.0003) in negative cases. No survival difference was found according to Ezrin expression. By multivariate analysis, nuclear expression of CXCR4 and IGF-1R was confirmed independent adverse prognostic factor for SS patient survival linked to the use of chemotherapy. CONCLUSIONS: Our findings have important potential implications demonstrating that together with clinical prognostic factors such as radiotherapy and age, CXCR4 and IGF-1R negatively influences survival in patients with localized SS. We believe that further studies addressed to the effects of CXCR4 and IGF-1R inhibitors on cell viability and function are needed to plan new and more appropriate SS treatments

Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression

<p>Abstract</p> <p>Background</p> <p>Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone.</p> <p>Results</p> <p>Using parallel oligonucleotide array platforms, shared orthologues between species were identified and normalized. The osteosarcoma expression signatures could not distinguish the canine and human diseases by hierarchical clustering. Cross-species target mining identified two genes, interleukin-8 (<it>IL-8</it>) and solute carrier family 1 (glial high affinity glutamate transporter), member 3 (<it>SLC1A3</it>), which were uniformly expressed in dog but not in all pediatric osteosarcoma patient samples. Expression of these genes in an independent population of pediatric osteosarcoma patients was associated with poor outcome (p = 0.020 and p = 0.026, respectively). Validation of <it>IL-8 </it>and <it>SLC1A3 </it>protein expression in pediatric osteosarcoma tissues further supported the potential value of these novel targets. Ongoing evaluation will validate the biological significance of these targets and their associated pathways.</p> <p>Conclusions</p> <p>Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapies.</p