Sarcoma Family Research Articles

Gastrointestinal Stromal Tumors "GIST": status and news through our experience on 54 cases and review of literature

Les Tumeurs Stromales Gastro-intestinales « GIST » sont une forme très rare de cancers du tube digestif appartenant à la famille des sarcomes. Le but de ce travail est d'établir le profil épidémiologique et évolutif ainsi que les difficultés diagnostique et thérapeutique de cette pathologie maligne prise en charge dans un pays en développement. Une Etude rétrospective étalée sur 8 ans de Janvier 2002 à Mars 2010, a été mené au Service de Radiothérapie et d'Oncologie du CHU de Casablanca (Maroc) ayant colligée 54 cas de tumeurs stromales gastro-intestinales. L'âge moyen de nos patients était de 55 ans. Le délai moyen d'évolution était de 11 mois (0-72 mois). La biopsie a permis de confirmer le diagnostic dans 14 cas et la chirurgie dans 40 cas. La principale forme histologique était fusiforme (92,6%). Les GIST dans notre série avaient une taille tumorale moyenne de 12,5 cm avec un C-Kit positif dans 52 cas. Le risque évolutif a pu être établi dans 47 cas dont 39 avaient un risque élevé. La chirurgie était le principal traitement des patients de notre sérieAprès un recul moyen de 31 mois, la moitié des patients évaluables de notre série (n=19) est en rémission complète maintenue, le tiers (n=13) est décédé alors que le quart (n=8) présente une récidive locale et /ou métastatique. Quoique les recommandations soient éditées pour la prise en charge de ces tumeurs, ces dernières soulèvent encore de nombreux problèmes aussi bien diagnostiques que thérapeutiques dans notre contexte.

VEGF-blockade of localized Ewing’s sarcoma based on angiogenesis markers in pretreatment tumor tissue

A third of patients with localized (non-metastatic) forms of tumors of the Ewing sarcoma family (ES) have resistance to modern systemic therapy regimens, which leads to a relapse of the disease. Forecasting such cases for the purpose of timely intensification of treatment is possible by studying the biology of the tumor process and in particular angiogenesis (AG) – the process of formation of the tumor by the own vascular network. Earlier, we found that the level of AG markers (TFPI2 mRNA expression (tissue factor inhibitor) and the ratio of VEGFA165/VEGFA189 vascular endothelial growth factor isoforms) in the tumor tissue prior to treatment can differentiate patients. Previously we have established the ability to predict poor outcome based on mRNA expression levels of both TFPI2 (tissue factor pathway inhibitor 2) and VEGFA165/VEGFA189 (vascular endothelial growth factor isoforms) ratio in pretreatment tumor tissue, it makes it possible to differentiate patients from localized ES into groups of favorable and unfavorable outcome of the disease. The aim of this study was to intensify treatment by blockade of AH for patients with an adverse outcome predicted by the level of AH markers. VEGF-blockade was used to enhance the therapeutic effects for patients with a predicted adverse outcome. 29 patients with localized forms ES included in the study. For patients with adverse prognosis (51.7 %) standard chemotherapy has been strengthened through bevacizumab (VEGF inhibitor). 5-years Event-free survival (EFS) for patients with adverse prognosis was 66.7 % for patients with good prognosis – 100 %, for all patients EFS rate was 82.4 %. EFS of the combined cohort of patients was 82.8 %. It was shown that anti-angiogenic therapy can be effective in patients with localized forms of ES with a predictable (based on the level of AH markers) adverse outcome of the disease.

ENDOPROSTHESIS OF THE SHOULDER JOINT IN METASTATIC LESIONS OF THE PROXIMAL HUMERUS DURING IMMUNOSUPPRESSIVE THERAPY

The incidence of primary malignant tumors of the skeleton is an average of 1.5 for men, for women – 0.9 per 100 000 population. Morphologically most common are: osteosarcoma (55-63%), chondrosarcoma (17–25%) and Ewing’s sarcoma family of tumors (8–15%). Metastatic lesions of long bones occurs 2-4 times more common than primary tumors and often are diagnosed with breast cancer in 65–73%, of prostate cancer in 56–68% and lung cancer in 30–36% of patients. World Data standard treatment for patients is a combined approach, one of the stages is a surgical treatment. In modern oncoorthopedics the standard of surgical treatment of patients with tumor lesions of bone is the conduction of segmental bone resection and oncological arthroplasty. However, just as with other surgical interventions, in arthroplasty with large joints that is associated with the introduction of foreign material into the body, there are complications which usually are infectious by nature. Complications associated with the continuous use of immunosuppressive therapy include bacterial and viral infections. It must be emphasized that in the context of immunosuppression bacterial infection is much greater and is accompanied by greater mortality than in patients without immunosuppression. The frequency of complications in patients who undergo total joint replacement after organ transplantation can be significantly reduced by the correction of metabolic disorders, the purpose of broad-spectrum antibiotics in the perioperative period and careful rehabilitation. It is necessary to work closely with the transplantologists. Also the method of using a local antibiotic administered directly to the site of surgery can be used. This method has significant advantages because of the high local concentrations with minimal risk of systemic toxicity. In this paper we present a clinical case of performing resection of the proximal humerus to the shoulder joint arthroplasty in patient on immunosuppressive therapy.

Ewing Sarcoma of the Bone With EWS/FLI1 Translocation After Successful Treatment of Primary Osteosarcoma

Although prognosis in patients with localized osteosarcoma has been dramatically improved by the introduction of multiple chemotherapy agents known as combination chemotherapy, there is growing concern about the development of secondary malignant neoplasms. We report the case of a 13-year-old girl in whom the diagnosis of Ewing sarcoma of bone localized on the shaft of left femur was made 2 years after successful treatment without radiotherapy for osteosarcoma of right proximal femur. EWS-FLI1 fusion gene was detected by reverse transcriptase-polymerase chain reaction. To our knowledge, this is the first case with Ewing sarcoma of the bone as a secondary malignant neoplasm developed in osteosarcoma survivor. We collected 15 cases, included this case, with secondary Ewing sarcoma family of tumor by utilizing the PubMed search and might consider the causes of this secondary cancer.

506PD Ewing Sarcoma family tumors of vertebral column treated with uniform chemotherapy protocols: Experience from a tertiary cancer care center

506PD Ewing Sarcoma family tumors of vertebral column treated with uniform chemotherapy protocols: Experience from a tertiary cancer care center

507PD Clinical presentation, treatment, outcome, and prognostic factors of non-metastatic Ewing sarcoma family of tumors: A single centre experience of 35 patients

507PD Clinical presentation, treatment, outcome, and prognostic factors of non-metastatic Ewing sarcoma family of tumors: A single centre experience of 35 patients

506PD Ewing Sarcoma family tumors of vertebral column treated with uniform chemotherapy protocols: Experience from a tertiary cancer care center

506PD Ewing Sarcoma family tumors of vertebral column treated with uniform chemotherapy protocols: Experience from a tertiary cancer care center

507PD Clinical presentation, treatment, outcome, and prognostic factors of non-metastatic Ewing sarcoma family of tumors: A single centre experience of 35 patients

507PD Clinical presentation, treatment, outcome, and prognostic factors of non-metastatic Ewing sarcoma family of tumors: A single centre experience of 35 patients

EWSR1/ELF5 induces acute myeloid leukemia by inhibiting p53/p21 pathway.

The Ewing sarcoma breakpoint region 1 (EWSR1) gene is known to fuse with various partner genes to promote the development of the Ewing sarcoma family of tumors and other sarcomas. In contrast, the association of EWSR1 chimeric fusion genes with leukemia has rarely been reported. We identified a novel EWSR1‐associated chimeric fusion gene in a patient with acute myeloid leukemia harboring 46, XY, t (11; 22) (p13; q12) karyotype abnormality. The patient was refractory to intensified chemotherapy including hematopoietic stem cell transplantation. Total RNA paired‐end sequencing identified a novel chimeric fusion gene as EWSR1/ELF5, a member of the E26 transformation‐specific transcription factor family. Transduction of EWSR1/ELF5 to NIH3T3 cells induced transformation by attenuating with the p53/p21‐dependent pathway. The injection of EWSR1/ELF5‐transduced NIH3T3 cells into NSG‐SCID mice systematically induced the development of tumors in vivo. These results revealed the oncogenic potency of EWSR1/ELF5.

Kidney Cancers in Adolescents & Young Adults

Kidney Cancers in Adolescents & Young Adults

Factors affecting survival outcomes of patients with non-metastatic Ewing’s sarcoma family tumors in the spine: a retrospective analysis of 63 patients in a single center

Little information has been published in the literature regarding survival outcomes of patients with Ewing's sarcoma family tumors (ESFTs) of the spine. The purpose of this study is to explore factors that may affect the prognosis of patients with non-metastatic spinal ESFTs. A retrospective analysis of survival outcomes was performed in patients with non-metastatic spinal ESFTs. Univariate and multivariate analyses were employed to identify prognostic factors for recurrence and survival. Recurrence-free survival (RFS) and overall survival (OS) were defined as the date of surgery to the date of local relapse and death. Kaplan-Meier methods were applied to estimate RFS and OS. Log-rank test was used to analyze single factors for RFS and OS. Factors with p values ≤0.1 were subjected to multivariate analysis. A total of 63 patients with non-metastatic spinal ESFTs were included in this study. The mean follow-up period was 35.1 months (range 1-155). Postoperative recurrence was detected in 25 patients, and distant metastasis and death occurred in 22 and 36 patients respectively. The result of multivariate analysis suggested that age older than 25 years and neoadjuvant chemotherapy were favorable independent prognostic factors for RFS and OS. In addition, total en-bloc resection, postoperative chemotherapy, radiotherapy and non-distant metastasis were favorable independent prognostic factors for OS. Age older than 25 years and neoadjuvant chemotherapy are favorable prognostic factors for both RFS and OS. In addition, total en-bloc resection, postoperative chemotherapy, radiotherapy and non-distant metastasis are closely associated with favorable survival.

Ewing sarcoma family of tumors in children younger than 10 years of age.

Few data exist regarding the clinical characteristics and outcome of young children with Ewing sarcoma family of tumors (ESFT). We reviewed the records of ESFT patients at our institution younger than 10 years of age at diagnosis. Forty-two patients were identified. Median age was 6.4 years (range 0.6-9.5 years). Most patients had T2 (>5 cm) tumors (n = 31; 74%). Most common primary site was the extremity (n = 17; 41%). Seven patients (17%) had metastasis at diagnosis. For local tumor control, 20 patients had surgery only, 13 had radiation therapy only, and 6 had surgery plus radiation. Surgical margin status was negative in 19 patients (73%). Median follow-up was 4.7 years (range 0.7-29.7 years), and 5-year relapse-free survival (RFS) and overall survival (OS) estimates were 67% (95% CI: 53-84%) and 82% (95% CI: 71-95%), respectively. Metastasis at presentation was the only significant predictor for decreased RFS (P = 0.008) and OS (P = 0.01). A trend was seen for T2 tumors with worse OS (P = 0.09). Patients younger than 10 years of age with ESFT may have a better OS than older patients, but further study of a homogeneously treated larger cohort is needed.

Molecular cytogenetic characterization of two established ESFT cell lines.

Ewing's sarcoma/primitive neuroectodermal tumor/Askin's tumor (Ewing`s sarcoma family of tumors: ESFT) is the most common type of malignant tumor of bone and soft tissue in children and young adults, and morphologically is a member of a group of small round cell tumors. We report, here, on the establishment of two human ESFT cell lines, FU-PNET-3 and FU-PNET-4, from the iliac and the chest wall, respectively, the cells of both cell lines were tumorigenic in immunodeficient mice. Histologically, both original and xenograft tumors and cultured cells were composed of small round cells with positive immunoreactivity for CD99 and Nkx2.2. Molecular biological examination demonstrated chimeric transcripts of EWSR1 exon 7 to FLI1 exon 6 in FU-PNET-3 cells, and EWSR1 exon 10 to FLI1 exon 6 in FU-PNET-4 cells. Cytogenetic analysis revealed chromosome translocation t(11;22)(q24;q12) and some secondary changes in both cultured cells. These histological, molecular biological, and cytogenetical findings indicate ESFT in both cell lines. ESFT is well studied, but its recurrent fusion genes are heterogeneous and its biological behaviors are unclear. The FU-PNET-3 and FU-PNET-4 cell lines have been well examined and may become useful tools for studying the genetic and biological behavioral properties of ESFT.

Evaluation of minimal disseminated disease in cryopreserved ovarian tissue from bone and soft tissue sarcoma patients.

What is the risk of finding malignant cells in cryopreserved ovarian tissue from sarcoma patients? Minimal disseminated disease (MDD) was not detected in frozen-thawed ovarian tissue from 26 patients by any of the sensitive methods applied. In case of leukemia, the risk of malignant cell transmission through the graft is well known and widely documented. However, for bone cancer, like Ewing sarcoma or osteosarcoma, only a small number of case reports, have been published. These cancers often affect prepubertal girls, in whom ovarian tissue cryopreservation and transplantation is the only option to preserve fertility. The presence of malignant cells in cryopreserved ovarian tissue from patients with bone/soft tissue sarcoma was investigated with disease-specific markers for each patient, using immunohistochemistry (IHC), FISH and real-time quantitative RT-PCR (qPCR), with the original tumor serving as a positive control. Forty-eight sarcoma patients were enrolled in the study, 12 of whom subsequently died. In each case, tissue from the primary tumor was investigated in order to identify markers (immunohistochemical and/or molecular) to analyze the ovarian tissue case by case. Ovarian tissue from osteosarcoma (n=15), liposarcoma (n=1) and undifferentiated sarcoma (n=5) patients could not be evaluated, as no specific markers were detected by FISH or sensitive IHC in any of their primary tumoral tissue. One patient with Li-Fraumeni syndrome was also excluded from the study. IHC analyses were therefore performed on ovarian tissue from 26 patients and qPCR on 19. The primary tumors involved were Ewing sarcoma family of tumors (n=14), rhabdomyosarcoma (n=7), synovial sarcoma (n=2), clear cell sarcoma (n=2) and a malignant peripheral nerve sheath tumor (n=1). MDD was not detected in any of the 26 analyzed samples using sensitive techniques in this largest reported series, even from patients who subsequently died and/or those who presented with metastasis (11/26), hence the most aggressive forms of bone cancer. Indeed, anti-CD99 IHC and PCR performed on patients presenting with Ewing sarcoma family of tumors (n=14) was negative in all cases. In patients with soft tissue sarcoma (n=12) primitive tumor markers were detected by IHC and were negative in ovarian tissue. PCR could only be performed in 6/12 of these patients, again proving negative. Cryopreserved ovarian fragments to be transplanted cannot be tested, so this analysis of malignant cells cannot guarantee that all cryopreserved fragments will not contain any disseminated disease. Moreover, molecular markers are not readily available for all types of tumors. These results are reassuring regarding the risk of malignant cells in the ovary for transplantation, as the study involves a large series including different types of sarcomas. We believe this will help clinicians in their patient counseling for fertility preservation and restoration. This work was supported by the Fonds National de la Recherche Scientifique de Belgique-FNRS under Grants Nos 7.4578.14 (Télévie to MS) and 5/4/150/5 to MMD. The authors declare no competing financial interests.

Loss of Ewing sarcoma EWS allele promotes tumorigenesis by inducing chromosomal instability in zebrafish.

The Ewing sarcoma family of tumors expresses aberrant EWSR1- (EWS) fusion genes that are derived from chromosomal translocation. Although these fusion genes are well characterized as transcription factors, their formation leaves a single EWS allele in the sarcoma cells, and the contribution that the loss of EWS makes towards disease pathogenesis is unknown. To address this question, we utilized zebrafish mutants for ewsa and tp53. The zebrafish tp53(M214K)w/m line and the ewsaw/m, zygotic ewsam/m, and Maternal-Zygotic (MZ) ewsam/m lines all displayed zero to low incidence of tumorigenesis. However, when the ewsa and tp53 mutant lines were crossed with each other, the incidence of tumorigenesis drastically increased. Furthermore, 27 hour post fertilization (hpf) MZ ewsam/m mutant embryos displayed a higher incidence of aberrant chromosome numbers and mitotic dysfunction compared to wildtype zebrafish embryos. Consistent with this finding, tumor samples obtained from ewsam/m;tp53w/m zebrafish displayed loss of heterozygosity (LOH) for the wildtype tp53 locus. These results suggest that wildtype Ewsa inhibits LOH induction, possibly by maintaining chromosomal stability. We propose that the loss of ewsa promotes tumorigenesis, and EWS deficiency may contribute to the pathogenesis of EWS-fusion-expressing sarcomas.

Metastatic extraskeletal Ewing's sarcoma treated with trabectedin: A case report.

The Ewing's sarcoma family of tumors (ESFT) comprises a number of rare malignant tumors. Standard first-line treatment for patients with these tumors includes chemotherapy with a five-drug regimen of vincristine, doxorubicin (Adriamycin®) and cyclophosphamide, alternating with ifosfamide and etoposide (VAC/IE). In cases of inadequate response, there are a number of second-line regimens available. However, further treatment options are required for those patients with disease unresponsive to standard treatment. Trabectedin is a novel treatment option for patients with ESFT. The present study reports the case of a Caucasian 69-year-old female patient who presented with a soft tissue mass on the chest wall that had developed 7 months earlier. A computed tomography scan revealed a 9×8×7-cm mass on the anterior chest wall above the pectoral muscle. Histopathological evaluations and molecular analysis indicated that it was consistent with a metastatic extraskeletal Ewing's sarcoma. The patient was treated with an alternating VAC/IE regimen; however, an inadequate response was observed. The patient received second-line treatment with a gemcitabine and dacarbazine combination regimen, but the disease progressed. Subsequently, treatment with trabectedin (1.5 mg/m2 as a 24-h continuous infusion every 3 weeks) was initiated. Trabectedin treatment resulted in long-lasting (18 months) progression-free survival. It is vital that novel drugs continue to being developed for patients with ESFT following progression subsequent to standard chemotherapy. The current report presents a case of a patient with metastatic, pre-treated Ewing's sarcoma achieving disease stabilization with trabectedin. Based on these results and the observed tolerability profile, trabectedin represents an alternative treatment for patients with ESFT. Further studies are required in order to determine the efficacy of trabectedin as monotherapy or in combination with other drugs. It is also important to identify which tumor subtypes, specific translocations and patient profiles will benefit the most from treatment with trabectedin.

The Ewing's Sarcoma Family of Tumors of Urinary Bladder: A Case Report and Review of the Literature.

Only 15 cases of Ewing's Sarcoma (EWS) family of tumors of urinary bladder have been documented in the literature to date. We presented here a 38 year-old female with primary urinary bladder EWS with no distant metastases. She had presented with macroscopic hematuria and had undergone transurethral resection of the tumor within the following week. Microscopic examination revealed a tumor diffusely infiltrating the lamina propria and muscularis propria under an intact urothelium, which was composed of small round blue cells with scant cytoplasm, monotonous round or oval nuclei, stippled chromatin and small nucleoli. Immunohistochemistry showed strong vimentin, synaptophysin and membranous CD99 expression by the tumor. Fluorescent in situ hybridization analysis displayed the EWSR1 rearrangement. Radical cystectomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy, extended lymph node dissection, and ileal conduit were performed. As adjuvant chemotherapy, she received vincristine, doxorubicin, cyclophosphamide and mesna, alternating with courses of etoposide, iphosphamide and mesna. She is alive and well with no evidence of disease 14 months after the surgery. Surgery supported with chemotherapy should be considered as an option, especially in advanced Ewing's sarcoma family of tumors of urinary bladder.

Abstract 1183: PPARgamma agonist promotes adipocytic differentiation and potentiates the activity of trabectedin in myxoid liposarcoma

Abstract Trabectedin (ET-743, Yondelis) is a marine alkaloid isolated from the tunicate Ecteinascidia turbinata, approved in Europe and US for the 2nd line therapy of soft tissue sarcomas. It is particularly effective against myxoid liposarcoma, a specific histological subtype within the family of adults soft tissue sarcomas. More than 90% of usual myxoid/round cell liposarcomas (MRCLS) are characterized by the chromosomal translocation t(12;16) (q13; p11), which produces the FUS-CHOP oncogene. Different chimera subtypes seem to respond differently to trabectedin in clinical setting. Trabectedin was able to remove FUS-CHOP type I, II and III from its own target genes but it causes adipocytic maturation and tumor regression only in type I and II, not in type III MRCLS (Di Giandomenico et al, Oncogene, 2014 Oct 30; 33(44): 5201-10). Pioglitazone is a PPARgamma agonist with pro-differentiation effects in different cancer types included liposarcomas (Tontonoz P. et al, Proc Natl Acad Sci U S A. 1997 Jan 7;94(1): 237-41). The aim of the study is to evaluate the efficacy of the combination of trabectedin with pioglitazone in type III myxoid liposarcoma xenografts. ML006 and ML004 type III MRCLS xenografts mice were treated with trabectedin 0.15 mg/kg iv every seven days for three times or pioglitazone 150 mg/kg po daily for 28 days or with their combination. For antitumor activity evaluation, tumor growth was measured with a caliper and the tumor weights (1 mm3 = 1 mg) were calculated with the formula: length × (width)2/2. Fifteen days after the last dose of trabectedin and 4 h after the last dose of pioglitazone tumors were collected from a separate group of mice to perform histological and molecular analyses. Trabectedin and pioglitazone as single agents have a comparable antitumor activity on these models with T/C around 40-50% with no tumor regression observed. In the combination groups an impressive and long lasting tumor regression was observed in ML 006 xenograft, with an observed optimal T/C of 17%. In ML004 MRCLS model the combination of trabectedin and pioglitazone induced a minimal regression followed by a long lasting tumor stabilization, resulting in a T/C of 23%. The histological analyses showed adipocytic maturation in tumors treated with pioglitazone alone or in combination but not in samples from mice treated with trabectedin alone. In conclusion, the combination of trabectedin with pioglitazone was able to induce tumor regression and adipocytic maturation in type III myxoid liposarcoma xenografts that were only marginally sensitive to trabectedin alone. Chromatin Immunoprecipitation, gene expression profile and Western Blot analysis are on-going to unravel the molecular mechanism behind the potentiation of the antitumor efficacy observed with this combination. Citation Format: Ezia Bello, Roberta Frapolli, Simonetta Andrea Licandro, Silvia Brich, Laura Carrassa, Roberta Sanfilippo, Alessandro Gronchi, Paolo Casali, Silvana Pilotti, Maurizio D’Incalci. PPARgamma agonist promotes adipocytic differentiation and potentiates the activity of trabectedin in myxoid liposarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1183.

Abstract 2696: Four new brain tumor entities emerge from molecular classification of CNS-PNETs

Abstract CNS-primitive neuroectodermal tumors (CNS PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Histological diagnosis is complicated by morphological heterogeneity and divergent differentiation. Recent studies suggest the existence of molecular subgroups of CNS-PNETs sharing biological characteristics with other CNS tumors. To investigate this we have analyzed 323 fresh-frozen or paraffin-embedded institutionally diagnosed CNS-PNETs using DNA methylation and expression arrays. Data were compared to 211 reference cases of other pediatric and adult brain tumors representing more than 20 well-known entities. DNA methylation and gene expression patterns showed that a significant proportion of CNS PNETs display molecular profiles indistinguishable from those of various other well defined CNS tumor entities. Hallmark genetic alterations for each of these well-defined entities, such as amplification of 19q13.42, mutations in IDH1 or H3F3A, mutations/deletions of the SMARCB1 locus, or RELA fusions, were frequently detected among the reclassified cases. From the remaining fraction of CNS PNETs we have identified four new CNS tumor entities, each associated with a unique recurrent genetic alteration and distinct histopathological and clinical features. Based on these findings we designated these four new entities as “CNS neuroblastoma with FOXR2 activation (CNS NB FOXR2)”, “CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT CIC)”, “CNS high grade neuroepithelial tumor with MN1 alteration (CNS HGNET MN1)”, and “CNS high grade neuroepithelial tumor with BCOR alteration (CNS HGNET BCOR)”. Our findings reinforce the importance of incorporating molecular information into the next revision of the WHO classification of CNS tumors, and warrant a replacement of the term “CNS PNET” with biologically specific designations. Our study provides an innovative framework for improving diagnostic accuracy and prognostication in malignant CNS tumors. The approach is amenable to retrospective analyses of patients treated with current regimens and will facilitate the design of more meaningful clinical trials for patients with malignant brain tumors. Citation Format: Dominik Sturm, Brent Orr, Umut H. Toprak, Volker Hovestadt, David T.W. Jones, David Capper, Peter Lichter, Andrey Korshunov, Stefan M. Pfister, David W. Ellison, Marcel Kool. Four new brain tumor entities emerge from molecular classification of CNS-PNETs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2696.

The utility of SATB2 immunohistochemical expression in distinguishing between osteosarcomas and their malignant bone tumor mimickers, such as Ewing sarcomas and chondrosarcomas

SATB2 is commonly expressed in osteosarcomas. Although apparently being a valuable diagnostic marker for differentiating between small cell osteosarcoma (SCO) and other small round cell tumors of bone, for instance Ewing sarcoma family of tumors (ESFT), it has not been tested in a large series of ESFT and chondrosarcomas so far. We studied the immunohistochemical expression of SATB2 in 42 osteosarcomas, 31 chondrosarcomas, and 371 genetically confirmed ESFT. SATB2 positivity was detected in 90.4% of osteosarcomas, 87.5% of SCO, 91.3% of osteoblastic osteosarcomas, and in all chondroblastic and parosteal osteosarcomas. The osteoblastic and SCO subtypes expressed SATB2 more intensely than other histological types. SATB2 was expressed in 46.6% of chondrosarcomas, and in 1.3% of ESFT. Sensitivity and specificity of SATB2 immunoexpression were 90.4% and 95.3%, respectively. The positive and negative predictive values in osteosarcoma diagnosis were 66.6% and 98.9%, respectively.In chondrosarcoma, SATB2 immunoexpression was more frequent and intense in high-grade chondrosarcoma (Grade III) and uncommon in chondrosarcoma grade I. SATB2 positivity was detected in 55.6% of chondrosarcomas grade II. SATB2 apparently cannot distinguish between chondroblastic osteosarcoma and high-grade chondrosarcoma. Nevertheless, SATB2 is frequently expressed in osteogenic tumors, but is rarely positive in ESFT, and with the support of CD99 expression and specific molecular studies, it is very useful for distinguishing between these two lesions. Although SATB2 immunoexpression helps to distinguish osteosarcoma from their mimickers, the identification of malignant osteoid matrix formation and the integration of clinical and radiological data remain the corner stone of osteosarcoma diagnosis and as yet no antibody has equalled the diagnostic value of this important morphologic hallmark.