Marina Nikitovic

Values of MMP-2 and MMP-9 in Tumor Tissue of Basal-Like Breast Cancer Patients

Gelatinase A (MMP-2) and gelatinase B (MMP-9) are proteolytic enzymes involved in process of tumor invasion, and they are considered as possible tumor markers in breast cancer patients. In this study, we measured activity of latent and active form of MMP-2 and MMP-9 in tumor and adjacent tissue of 60 breast cancer patients by SDS-PAGE zymography. The activity of both form of gelatinases significantly increased with each advancing clinical stage of disease. ProMMP-9 and aMMP-9 activity in tumor tissue shows a positive association with tumor size. Patients with lymph node involvement have higher proMMP-2, aMMP-2 and aMMP-9 activity than node negative patients. Steroid receptor-negative tumors had enhanced aMMP-2 and aMMP-9 activity. Patients with basal-like cancers had higher proMMP-2 tumor activity and aMMP-2 adjacent tissue activity compared to patients with luminal A tumors. Patients with negative hormone receptors are associated with increased activity of both form of gelatinases in adjacent tissue. Reported increased activity of MMP-2 in tumor and adjacent tissue of basal-like tumors implicates that MMP-2 might have a role in aggressive biology of basal-like cancers. Additional investigations regarding molecular pathways in adjacent tissue could give better insight into aggressive nature of basal-like carcinomas.

The Influence of Adjuvant Radiotherapy in Atypical and Anaplastic Meningiomas: A Series of 88 Patients in a Single Institution

OBJECTIVE Atypical and anaplastic meningiomas (World Health Organization classification grade II and III) represent a small and heterogeneous subgroup of meningiomas that has a more aggressive biological nature and higher frequency of recurrence. The atypical form accounts for 4.7%-7.2%, whereas the anaplastic type accounts for 1%-2.8% of all meningiomas. The aim of this study is to evaluate the role of postoperative radiotherapy on overall survival and progression-free survival in patients operated for atypical and anaplastic meningiomas. METHODS A retrospective analysis of the patients operated at the Clinic of Neurosurgery, Clinical Center of Serbia, Belgrade, between January 1, 1995 and December 31, 2006 was performed. In that period 88 lesions met the histologic criteria for atypical (75) and anaplastic (13) meningiomas. Postoperative radiotherapy was conducted in 63.6% of patients. RESULTS At a median follow-up of 67.4 months the overall survival was 68 months and the 5-year survival was about 54.5%. The median survival was 76 months with surgery and adjuvant radiotherapy and 40 months with surgery alone (log rank = 7.4; P = 0.006). Recurrent disease occurred in 58 patients (65.9%). Median time between first surgery and tumor recurrence in patients undergoing radiotherapy was 51 months, whereas in the nonirradiated group it was 24 months (log rank = 17.7; P < 0.001). Multivariate analysis identified as recurrence-predicting factors anaplastic histotype (hazard ratio = 2.9; P = 0.003) and postoperative radiotherapy (hazard ratio = 4.5; P < 0.001). CONCLUSIONS The addition of adjuvant radiotherapy to surgery for atypical and anaplastic meningiomas resulted in a clinically meaningful and statistically significant survival benefit.

INCIDENCE OF PRIMARY CENTRAL NERVOUS SYSTEM TUMORS AMONG CHILDREN IN BELGRADE (SERBIA), 1991–2004

The aim of this survey was to estimate the incidence of primary CNS tumors among children aged 0–14 in Belgrade during the period 1991–2004. Incidence rates were age-adjusted according to the world standard population. The average age-adjusted incidence rates were 3.4/100,000 for boys, 2.4/100,000 for girls, and 2.9/100,000 for both genders. There was a nonsignificant tendency toward increased CNS tumor incidence (y = 2.547 + 0.052x, p =. 549). The age-specific incidence rates were 3.0/100,000 (0–4 years), 2.2/100,000 (5–9 years), and 3.8/100,000 (10–14 years). Among the population aged between 0 and 14, the cumulative probability of acquiring primary CNS tumors was 1 per 1961 for boys and 1 per 2778 for girls. Astrocytoma was the most common pathohistological type of primary CNS tumors accounting for 41.5% of cases.

Positive enhancement integral values in dynamic contrast enhanced magnetic resonance imaging of breast carcinoma: Ductal carcinoma in situ vs. invasive ductal carcinoma

OBJECTIVES The aim of this study was to contribute to the standardization of the numeric positive enhancement integral (PEI) values in breast parenchyma, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and to evaluate the significance of the difference in PEI values between IDC and parenchyma, DCIS and parenchyma and IDC and DCIS. MATERIALS AND METHODS In the prospective trial, we analyzed the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of 60 consecutive patients with histologically confirmed unilateral DCIS (n=30) and IDC (n=30) and defined the PEI values (range; mean ± SD) for the lesions and the breast parenchyma. Tumor-to-non-tumor (T/NT) ratios were calculated for DCIS and IDC and compared. PEI color maps (PEICM) were created. The differences in PEI values between IDC and parenchyma and between DCIS and parenchyma were tested according to t-test. Analysis of variance (ANOVA) was used to test the differences between the mean PEI values of parenchyma, DCIS and IDC. RESULTS IDC showed highly statistically different PEI numeric values compared to breast parenchyma (748.7 ± 32.2 vs. 74.6 ± 17.0; p<0.0001). The same applied to the differences in the group of patients with DCIS (428.0 ± 25.0 vs. 66.0 ± 10.6; p<0.0001). The difference between IDC, DCIS and parenchyma were also considered highly statistically significant (p<0.0001) and so were the T/NT ratios for IDC and DCIS (10.1 ± 2.4 vs. 6.6 ± 1.4; p<0.0001). CONCLUSIONS PEI numeric values may contribute to differentiation between invasive and in situ breast carcinoma.

Bone Metastases in Medulloblastoma –Single Institution Experience

Background: Medulloblastoma has one of the highest rates of metastasis outside the central nervous system (CNS). Bone metastases are the most common lesions, although lymph node and visceral spread have also been reported. Objective: To present patients with bone metastasis in medulloblastoma and discuss their radiologic appearances and treatment approach. Patients and methods: From 1993 to 2008, 82 patients diagnosed with medulloblastoma were treated at the Institute for Oncology and Radiology of Serbia. Three (3.6%) developed extraneural metastasis (ENM). In primary treatment, patients were treated with surgery, craniospinal radiotherapy with local boost to tumor bed, and adjuvant chemotherapy [lomustine (CCNU) and vincristine]. Of the three patients with ENM, all developed bone metastases at the time of relapse. Relapse occurred within 17 to 42 months of initial diagnosis. Patients received secondary chemotherapy and palliative radiotherapy to the affected bone in two cases. Results: Among these three patients, case 1 had initially a solitary lytic lesion. Case 2 had diffuse blastic lesions and also bone marrow involvement. Case 3 had multiple mixed lytic-sclerotic lesions but later developed lymph node metastasis and metastases to both breasts, as well. All patients were without concurrent CNS involvement at the time of ENM. Unfortunately, after initial partial response, the three patients died at 24, 13, and 18 months after detection of metastases, respectively. Conclusion: With prolonged survival times in children with medulloblastoma, more emphasis should be placed on the possibility of systemic involvement. A greater understanding of the pathogenesis of the systemic metastases may be valuable in designing future, more aggressive multimodal therapy.

Fractal and Gray Level Cooccurrence Matrix Computational Analysis of Primary Osteosarcoma Magnetic Resonance Images Predicts the Chemotherapy Response

The prediction of induction chemotherapy response at the time of diagnosis may improve outcomes in osteosarcoma by allowing for personalized tailoring of therapy. The aim of this study was thus to investigate the predictive potential of the so far unexploited computational analysis of osteosarcoma magnetic resonance (MR) images. Fractal and gray level cooccurrence matrix (GLCM) algorithms were employed in retrospective analysis of MR images of primary osteosarcoma localized in distal femur prior to the OsteoSa induction chemotherapy. The predicted and actual chemotherapy response outcomes were then compared by means of receiver operating characteristic (ROC) analysis and accuracy calculation. Dbin, Λ, and SCN were the standard fractal and GLCM features which significantly associated with the chemotherapy outcome, but only in one of the analyzed planes. Our newly developed normalized fractal dimension, called the space-filling ratio (SFR) exerted an independent and much better predictive value with the prediction significance accomplished in two of the three imaging planes, with accuracy of 82% and area under the ROC curve of 0.20 (95% confidence interval 0–0.41). In conclusion, SFR as the newly designed fractal coefficient provided superior predictive performance in comparison to standard image analysis features, presumably by compensating for the tumor size variation in MR images.

Intramedullary Spinal Cord Germinoma: A Case Report and Review of Literature

Primary spinal cord germinomas are an extremely rare group of tumors, most commonly reported as single cases in young Japanese adults. They usually present as intramedullary lesions located in the thoracic and thoracolumbar spine. The importance of preoperative diagnosis lies in the fact that by using radiotherapy and chemotherapy, even without surgery, a good cure rate can be achieved in patients with spinal cord germinoma. These tumors, however, demonstrate unspecific imaging characteristics, and only some secrete tumor markers. Therefore, a diagnosis of these lesions before biopsy or resection with pathohistologic examination can be difficult. We present a case of a 28-year-old white man with intramedullary spinal cord germinoma. The tumor was resected completely with electrophysiological monitoring, without a biopsy and frozen section analysis. Postoperative radiotherapy also was part of the treatment. The patient has had no relapse 4.5 years after diagnosis; however, significant neurologic deficits remain. Although not as frequent in white patients, germinoma should be considered as differential diagnosis in cases of young adult patients with intramedullary tumor in the thoracic or thoracolumbar spine. Therefore, spinal mass surgery should commence with a biopsy and intraoperative frozen section analysis. In this way, attempting a gross total resection becomes unnecessary. With an approach of intraoperative biopsy and frozen section analysis, a considerable amount of postoperative neurologic deficits can be reduced.