Petra Dildey

CD31 angiogenesis and combined expression of HIF-1α and HIF-2α are prognostic in primary clear-cell renal cell carcinoma (CC-RCC), but HIFα transcriptional products are not: implications for antiangiogenic trials and HIFα biomarker studies in primary CC-RCC.

Hypoxia-inducible factors, HIF-1α and HIF-2α, are expressed in the majority of clear-cell renal cell carcinoma (CC-RCC). In vitro, HIFα isoforms regulate a differential set of genes, and their effects in vivo within CC-RCC tumours may affect outcome. The role of angiogenesis and HIFα transcriptional products, including those involved in cell metabolism and morphological dedifferentiation have not been extensively investigated and might have relevance to the development of antiangiogenic or anti-HIFα trials in primary CC-RCC, either before or after radical nephrectomy. We analysed 168 consecutive clear-cell renal tumours from 1983 to 1999 within tissue microarrays and assessed expression of HIF-1α and HIF-2α together with the protein expression of seven of their target genes (BNIP3, CA9, Cyclin D1, GLUT-1, LDH5, Oct-4 and VEGF). The expression of these factors was compared with patient overall survival and CD31 angiogenesis. We found that HIFα antigenicity deteriorated with the age of the paraffin block (P < 0.0001) and in tumours from 1983 to 1992 was deemed not to be reliable. Similar findings were found in aged archival osteosarcoma samples. This might have important implications for retrospective biomarker studies that rely on archival tissue material. HIF-1α(HIGH)/HIF-2α(LOW) tumours had a worse overall survival compared with HIF-1α(LOW)/HIF-2α(LOW) tumours (P = 0.04). Surprisingly, on multivariate analysis, high levels of CD31(+) angiogenesis was shown to be an independent prognostic marker of increased overall survival (P = 0.003). We propose that better differentiation of vascular endothelium may be a reflection of a greater production of vessel stabilization factors versus pro-angiogenic factors, and therefore a less aggressive phenotype.

A rare cause of spinal cord compression: imaging appearances of gout of the cervical spine

Gout is a metabolic disorder typically affecting the peripheral joints, more commonly in males. Spinal involvement is uncommon and is usually associated with hyperuricemia. We present the imaging findings of a case of spinal gout in a female patient with no previous history of hyperuricaemia, involving multiple spinal segments.

Lipoma or liposarcoma? A cautionary case report

MERRF syndrome (myoclonic epilepsy with ragged-red fibres) is a mitochondrial encephalomyopathy characterised by a mixed seizure disorder and myoclonus. The condition is associated with multiple large cervical lipomas that often require surgical excision. Comprehensive clinical examination combined with pre-operative radiographic imaging is vital in such cases to help differentiate benign fatty masses from potential liposarcomas. We describe a case in which a lipoma-like liposarcoma was identified following excision of what was expected, on clinical and radiological grounds, to be a lipoma. This case highlights the potential for sarcomatous changes in suspicious lipomas, and the key role that imaging plays in differentiating benign from malignant.

Cryptic EWSR1-FLI1 fusions in Ewing sarcoma: potential pitfalls in the diagnostic use of fluorescence in situ hybridization probes.

Detection of EWSR1 translocations - particularly t(11;22)(q24;q12) - is of great value in the differential diagnosis of the Ewing family of tumors. We report two cases that highlight the problems and pitfalls of identifying Ewing tumors using conventional chromosome analysis and a commercial EWSR1 fluorescence in situ hybridization (FISH) probe. In both cases, the tumor karyotype was abnormal, but a visible t(11;22)(q24;q12) was not present. The commercial EWSR1 break-apart probe was not split in either case. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, however, identified EWSR1-FLI1 fusion transcripts in both tumors, and the gene fusions were corroborated by FISH analysis with in house probes and confirmed by sequencing RT-PCR products. The occurrence of cryptic EWSR1-FLI1 fusions mandates that RT-PCR should be performed, particularly in those cases in which the genetic findings are not in agreement with the histologic picture.

Congenital multifocal inflammatory pseudotumor: a case report

Inflammatory pseudotumor is an uncommon benign tumor found in various sites throughout the body. The etiology is unclear with evidence to support both neoplastic and infective processes. The authors present a case with several unique features. It represents the first reported case detected antenatally. The tumor was found separately within the abdomen and thorax. The thoracic component of the tumor was managed without resection or ablative treatment but showed spontaneous regression.

Surgical outcome and patterns of recurrence for retroperitoneal sarcoma at a single centre.

INTRODUCTIONnRetroperitoneal sarcoma is a surgically managed condition that can recur locally following macroscopically complete resection. Owing to the low incidence of the condition, advances in treatment are reported infrequently but complete compartmental resection and adjuvant or neoadjuvant radiotherapy are areas under investigation. Given the practical difficulty of randomised trials, observational data can highlight advantages from progressive treatment approaches.nnnMETHODSnA retrospective database of consecutive retroperitoneal sarcoma resections performed at a single referral centre between March 1997 and March 2013 was interrogated. Histological, radiological and clinical data were collected. Univariate and multivariate analyses for disease free and overall survival were performed to establish independent predictors of disease recurrence and patient survival.nnnRESULTSnA total of 79 patients underwent 90 resections (63 primary). The mean five-year overall and disease free survival rates were 55.3% and 24.8% respectively. Higher patient age, high tumour grade, presence of extraretroperitoneal disease and invasive tumour phenotype were found to significantly predict survival following multivariate analysis. Half (50%) of the tumours displayed invasive behaviour on histopathology and 42% of locoregional recurrence was intraperitoneal.nnnCONCLUSIONSnRetroperitoneal sarcoma is commonly an infiltrative tumour and often recurs outside of the retroperitoneum. These features limit the therapeutic impact of interventions that focus on gaining local control such as complete compartmental resection and radiotherapy. It seems likely that future advances in the management of this cancer will involve new systemic agents to treat this frequently systemic disease.

Pain and fracture after anterior cruciate ligament reconstruction caused by giant cell tumour of the distal femur

The causes of pain after an anterior cruciate ligament (ACL) reconstruction are numerous and may have complex origins. We present an unusual case in which pain after an ACL reconstruction developed secondary to a giant cell tumour of the bone occurring around a fixation screw in the distal femur, with an associated fracture through the femoral tunnel of a previously well-functioning reconstruction. We discuss the aetiology and the treatment of a complex clinical scenario.

Myxofibrosarcoma of the extremity and trunk: a multidisciplinary approach leads to good local rates of LOCAL control

AIMSnMyxofibrosarcomas (MFSs) are malignant soft-tissue sarcomas characteristically presenting as painless slowly growing masses in the extremities. Locally infiltrative growth means that the risk of local recurrence is high. We reviewed our experience to make recommendations about resection strategies and the role of the multidisciplinary team in the management of these tumours.nnnPATIENTS AND METHODSnPatients with a primary or recurrent MFS who were treated surgically in our unit between 1997 and 2012 were included in the study. Clinical records and imaging were reviewed. A total of 50 patients with a median age of 68.4 years (interquartile range 61.6 to 81.8) were included. There were 35 men; 49 underwent surgery in our unit.nnnRESULTSnThe lower limb was the most common site (32/50, 64%). The mean size of the tumours was 8.95 cm (1.5 to 27.0); 26 (52%) were French Fédération Nationale des Centres de Lutte Contre le Cancer grade III. A total of 21 (43%) had positive margins after the initial excision; 11 underwent further excision. Histology showed microscopic spread of up to 29 mm beyond macroscopic tumour. Local recurrence occurred in seven patients (14%) at a mean of 21 months (3 to 33) and 15 (30%) developed metastases at a mean of 17 months (3 to 30) post-operatively.nnnCONCLUSIONnHigh rates of positive margins and the need for further excision makes this tumour particularly suited to management by multidisciplinary surgical teams. Microscopic tumour can be present up to 29 mm from the macroscopic tumour in fascially-based tumours. Cite this article: Bone Joint J 2016;98-B:1682-8.

Mycobacterium avium-intracellulare: a rare cause of subacromial bursitis

Septic subacromial bursitis is an uncommon disorder with only a few reported cases in the literature. The most common causative organism is Staphylococcus aureus. We report the case of a 61-year-old female with a septic subacromial bursitis where the causative organism was found to be Mycobacterium avium-intracellulare (MAI). The diagnosis was only made following a biopsy, and we use this case to highlight the importance of recognising the need to consider a biopsy and aspiration in atypical situations.

Abstract 5580: Membrane-Type 1 Matrix Metalloproteinase (MT1-MMP): A predictive biomarker of chemotherapy response in osteosarcoma

INTRODUCTION: Osteosarcoma (OS) is the most common primary bone sarcoma and affects mainly teenagers & young adults. Although OS survival ∼70% when patients are treated with both chemotherapy and surgery, the improvement in cure rates over the last 25 years has been slow. Given that OS frequently present with lung micrometastasis, proteins which regulate OS cell invasion would be important to identify as putative prognostic/predictive biomarkers, as well as possible drug targets. Membrane-Type 1 Matrix Metalloproteinase (MT1-MMP) is one such protein. MT1-MMP is a membrane tethered MMP that is involved in the regulation of cell invasion since it is a collagenase and regulates MAPK/ERK dependent cell motility. Given that MT1-MMP expression can be upregulated by hypoxia, we investigated the expression of MT1-MMP, as well as hypoxia-inducible factor (HIF) isoforms in 76 primary tumor biopsies from patients who received standard MAP chemotherapy. In vitro, we investigated the effects of hypoxia on MT1-MMP. MATERIALS & METHODS: OS tumors were immunostained for MT1-MMP, HIF-1 and HIF-2. U2OS & SJSA-1 cell lines were used for in vitro studies. Immunoblotting & immunofluoroscence confocal microscopy were performed for MT1-MMP and HIFs at 1% O2 for 8, 12, 24 and 48 hours, compared with normoxia. RESULTS: 71/76 tumors were evaluable for MT1-MMP expression. MT1-MMP was identified in the cytoplasm and nuclei of OS tumors. Only 10/85 tumors demonstrated membrane expression. High expression of cytoplasmic (HR:0.32(95%CI:0.07-0.49);p=0.005) and nuclear (HR:0.21(95%CI:0.09-0.42);p 24 hours. In U2OS cells, confocal microscopy & subcellular fractionation immunoblots demonstrated that MT1-MMP and HIF-2 protein translocated to the nucleus from the cytoplasm at 1%O2. HIF-2 co-localized with MT1-MMP in nuclei, but HIF-1 did not. CONCLUSION: Nuclear MT1-MMP is a prognostic and predictive biomarker in OS patients treated with MAP chemotherapy. Since MT1-MMP does not contain a nuclear localization signal (NLS), the in vitro data points to the possibility that HIF-2 might have a novel function as a MT1-MMP nuclear transporter and that MT1-MMP nuclear migration, but not expression, is hypoxia dependent in vitro and might have pro-survival effects on OS cells in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5580. doi:1538-7445.AM2012-5580