Expression of heat shock proteins in brain tumors.

AIM: Heat shock proteins (HSP) are an evolutionary conserved family of proteins that serve as molecular chaperones, preventing the formation of nonspecific protein aggregates and assisting proteins in the acquisition of their native structures. Furthermore, HSPs have anti-apoptotic properties and have been found to be elevated in many human cancers; their overexpression has been associated with poor survival and response to therapy. In the present study we assessed the HSP expression in brain tumors. MATERIAL AND METHODS: Simultaneous detection of HSP27, HSP40, HSP60, HSP70, HSP90a, total Akt and phospho- Akt in 19 brain tumor specimens was performed using the multiplex bead array assay. RESULTS: There was expression of HSP27 (pSer82), HSP27 (pSer15), HSP40, HSP60, HSP70, HSP90a, total-Akt and phospho- Akt in both gliomas and meningiomas. Significantly higher levels of HSP70 and a trend towards higher levels of HSP40 were found in meningiomas compared to gliomas. There was a significant correlation between HSP27 (pSer82) and HSP27 (pSer15) expression and between HSP90a and both total-AKT and phospho- AKT. A significant correlation between HSP27 and total-AKT was observed. CONCLUSION: Since HSPss are an attractive target for anticancer therapy, further studies are needed in order to better assess their relationship with tumor aggressiveness and patient prognosis.

Immunohistochemical study of MRP5 expression in meningiomas.

PURPOSE: Meningiomas are the most common benign intracranial tumor, accounting for 30% of all primary intracranial tumors. Although benign meningiomas rarely recur after a complete resection, anaplastic tumors are associated with high recurrence rate and unfavorable outcome. In the current study, we investigated the expression of the multidrug resistance protein 5 (MRP5) in patients with meningiomas. METHODS: We retrospectively studied twenty patients with meningiomas that were treated surgically in our institute over a 3-year period. MRP5 protein expression was determined immunohistochemically. RESULTS: The immunohistochemical expression of MRP5 was observed only in anaplastic meningiomas. No MRP5 expression was detected in benign or atypical meningiomas. No significant correlation was found between MRP5 expression and Ki-67 index. After a mean follow-up period of 23 months, there were 4 cases of tumor recurrence. No correlation was found between extent of resection and tumor recurrence. CONCLUSION: Immunohistochemical MRP5 protein expression was observed only in anaplastic meningiomas. Further research is needed to clarify whether MRP5 is indicative of malignant pathological features in meningiomas and whether possible therapeutic implications exist.

Diffusion tensor and dynamic susceptibility contrast MRI in glioblastoma.

OBJECTIVE: We prospectively investigated the correlation between diffusion tensor (DTI), dynamic susceptibility contrast (DSC) perfusion MRI metrics and Ki-67 labelling index in glioblastomas. METHODS: We studied seventeen patients who were operated on for glioblastoma. DTI and DSC MRI were performed within a week prior to surgical excision. Lesion/normal ratios were calculated for the apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF) and relative mean transit time (rMTT) ratio. In the excised tumour specimens Ki-67 antigen expression was evaluated by the MIB-1 immunostaining method. RESULTS: A significant correlation was observed between Ki-67 index and ADC ratio (r = -0.528, p = 0.029) and FA ratio (r = 0.589, p = 0.012). rCBV and rMTT presented a trend towards significant correlation with Ki-67 index (r = 0.628, p = 0.07 and r = 0.644, p = 0.06 respectively). There was a trend towards better survival for patients with gross total tumour excision and FA values lower than 0.48 (p = 0.1 and p = 0.09 respectively). No significant correlation was found between ADC ratio, rCBV, rCBF, rMTT and overall survival. CONCLUSION: ADC ratio, FA ratio, rCBV and rMTT tumour/normal tissue ratios may represent indicators of glioma proliferation. FA values may hold promise for predicting survival in patients with glioblastoma.

Brain scintigraphy with 99mTc-tetrofosmin for the differential diagnosis of a posterior fossa tumor.

A 60-year-old woman harbouring a tumour in the cerebellum. Anatomic brain imaging by computed tomography and magnetic resonance imaging were not conclusive of the lesion's nature. Imaging by (99m)Tc-tetrofosmin single-photon emission tomography (SPET) showed increased radiotracer accumulation in the lesion, indicating a vascular supply, membrane permeability and cellular metabolic activity, which is suggested to facilitate tracer uptake by lesions located in the posterior fossa. The patient underwent surgery and haemangioblastoma was confirmed by histology. Differential diagnosis is discussed. (99m)Tc-tetrofosmin scintiscan contributed to diagnostic information.

(99m)Tc-Tetrofosmin brain SPECT in the assessment of meningiomas-correlation with histological grade and proliferation index.

Meningiomas account for about 30% of all intracranial tumors. Evaluation of their proliferation rate is useful for assessing their biological behavior. We evaluated prospectively whether (99m)Tc-Tetrofosmin ((99m)Tc-TF) uptake in meningiomas correlates with cellular proliferative activity and with tumor grade. We prospectively studied 18 meningioma cases. Brain single-photon emission computed tomography (SPECT) by (99m)Tc-TF was performed within a week prior to surgical excision. In the excised tumor specimens we assessed Ki-67 antigen expression. 14 of 18 patients had benign meningiomas, while the remaining four had anaplastic meningiomas. A significant correlation was found between both (99m)Tc-TF uptake and tumor grade (r = 0.722, P = 0.001) and between (99m)Tc-TF uptake and Ki-67 expression (r = 0.930, P < 0.001). There was a significant correlation between the intensity of tracer uptake and tumor recurrence at 1 year postoperative (r = 0.574, P = 0.02). This pilot study implies that (99m)Tc-TF brain SPECT could prove useful in differentiating benign from anaplastic meningiomas and is a potential indicator of their proliferative activity.

Olfactory colloid cyst.

Colloid cysts are rare intracerebral lesions that are predominantly located in the third ventricle. Extraventricular colloid cysts have only rarely been reported but so far there are no reports of a colloid cyst residing in the olfactory groove. A 74-year-old patient underwent a brain computed tomography scan for a mild head trauma that incidentally revealed a space-occupying lesion near the olfactory groove. Brain magnetic resonance imaging that ensued demonstrated a hyperintense lesion in T1, T2, and FLAIR sequences, without evidence of surrounding brain edema. To evaluate the metabolic status of the lesion, brain single-photon emission computed tomography with 99mTc-Tetrofosmin was then performed, revealing no tracer uptake, a finding consistent with benignity. Due to the diagnostic uncertainty the excision of the lesion was proposed. The patient underwent surgery and intraoperative a cyst was revealed. Furthermore the cyst seemed to erode the dura and due to its location there was an imminent danger for cerebrospinal fluid leak. Therefore a repair of the dura was performed and the cyst was excised totally. Histology verified the presence of a colloid cyst. Colloid cysts should be included in the differential diagnosis of lesions in the anterior fossa and although benign they may have an aggressive presentation by eroding the dura and producing CSF leak.

Estrogen receptor beta (ERbeta) protein expression correlates with BAG-1 and prognosis in brain glial tumours.

Estrogen receptor beta (ERbeta) is an important mediator of estrogen function in a variety of tissues. Its expression declines in breast, ovarian, prostatic and colon carcinomas as well as in astrocytic tumours. BAG-1 is a multifunctional protein with an important role in neoplasia and is possibly regulated by estrogen receptors. One of the direct targets of BAG-1 is HSP70. The purpose of this study was to analyse the expression pattern of these proteins in two distinct types of glial neoplasms, to investigate their possible correlation and probe their impact on prognosis. ERbeta, BAG-1 and HSP70 protein expression was monitored immunohistochemically in 66 cases of astrocytomas and 20 oligodendrogliomas. In astrocytic tumours low ERbeta expression correlated significantly with high grade (P < 0.001), higher expression of cytoplasmic BAG-1 (P < 0.001) and worse survival (log rank P = 0.02). Multivariate analysis revealed that ERbeta expression had a prognostic value for overall survival in these patients (Cox P = 0.03), which was not dependent on grade. There was also statistically significant association of BAG-1 nuclear expression with HSP70 cytoplasmic expression. Our results strengthen the hypothesis that ERbeta, BAG-1 and HSP70 play an important role in the pathogenesis and progression of glial neoplasms. Moreover, ERbeta expression in astrocytic tumors might be an important prognostic factor for survival.

Expression of vascular endothelial growth factor and its receptor, KDR/Flk-1, in soft tissue sarcomas.

The aim of the present study was to evaluate the association of vascular endothelial growth factor (VEGF) and its receptor, KDR/Flk-1, with tumor grade, microvessel density (MVD) and clinical outcome in patients with soft tissue sarcomas (STSs). Tissue specimens of 28 patients with STSs were analyzed immunohistochemically using specific monoclonal antibodies. Tissue samples were obtained prior to any treatment. Half of the STSs exhibited strong expression of VEGF that was associated statistically significantly with high tumor grade. Strong expression of KDR/Flk-1 was detected in only 2 sarcomas. No association was demonstrated between VEGF and KDR/Flk-1 expression. MVD was significantly associated with tumor grade and was higher in sarcomas with strong VEGF expression. Limited data on clinical outcome precluded solid analyses for an association with disease progression. This study provides further evidence on the role of VEGF and MVD in tumor aggressiveness in STSs.

Desmoid tumours of the extremities and trunk: a review of the literature.

Desmoid tumours are rare neoplasms that display local aggressiveness but no propensity to metastasise. They are mainly localized in the abdominal wall, the bowel, and the mesentery or in extra-abdominal sites such as the trunk and the extremities. Surgical resection is the main treatment modality in extremities and trunk, with the optional combination of radiotherapy and/or chemotherapy. However, these tumours have a high propensity for recurrent growth.

Expression of vascular endothelial growth factor and the adhesion molecule E-cadherin in non-small cell lung cancer.

Tumor angiogenesis plays an important role in tumor growth, maintenance and metastatic potential. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and a potent inducer of vessel permeability and angiogenesis in vivo. The aims of this study were to determine the value of VEGF expression in non-small cell lung cancer (NSCLC) and its association with vascularity, E-cadherin expression and clinicopathological variables. The expression of VEGF and E-cadherin was studied immunohistochemically in 88 NSCLC (48 squamous cell carcinomas, 30 adenocarcinomas, 10 large cell carcinomas). Vascularity was measured by the average number of CD31-positive cells (MVC: microvessel count). A high expression of VEGF (> or = 25% of cells) was observed in 75% and 73.34% of squamous cell carcinomas and adenocarcinomas, respectively, and in all cases of large cell carcinomas. High vascularity was associated with high VEGF expression. VEGF and MVC were correlated with low tumor differentiation (p < 0.001). Reduced E-cadherin expression (< 50% of cells) was noted in 61.36% of tumors and was associated with poor differentiation (p < 0.0001). The simultaneous high expression of VEGF and reduced expression of E-cadherin was correlated with tumor dedifferentiation (p < 0.001). In conclusion, the intratumoral VEGF expression correlates with tumor angiogenesis and histological differentiation. Reduced expression of E-cadherin is associated with poor tumor differentiation. Combined evaluation of VEGF and E-cadherin may become a useful indicator of NSCLC biological behavior and provide clinically important evidence on which to base treatment.