Ann Goussia

Evaluation of glioma proliferation by 99mTc-Tetrofosmin

The proliferation potential of gliomas is an indicator of their aggressiveness with significant implications in patient management and prognosis, but its assessment requires tissue sampling.1 We evaluated the relationship between glioma proliferation (as expressed by the Ki-67 index) and the uptake of the tumor-seeking radiotracer technetium-99m Tetrofosmin (99mTc-TF). Fourteen patients with a space-occupying lesion suspicious for glioma on structural brain imaging were prospectively enrolled. Scintitomographic (SPECT) imaging was performed and within a week the lesion was removed surgically; Ki-67 was assessed in the excised specimens by MIB-1 immunostaining. Three patients were excluded from the study because their lesions were proven metastatic. In the 11 patients eligible for analysis (7 males, 4 females; mean age 49.5 ± 7.5 years), the diagnosis was glioblastoma multiforme (6 cases), anaplastic astrocytoma (1), anaplastic oligodendroglioma (2), low-grade oligodendroglioma (1), and low-grade astrocytoma (1). We found a significant positive linear correlation between 99mTc-TF uptake and Ki-67 expression (r = 0.95, p = 0.001 [Spearman rank analysis]; Fig. 1 – 3). No significant correlation was observed between tracer uptake and tumor grade (r = 0.27, p = 0.420). The preliminary results of this pilot study, although deriving from a limited patient sample, propose that this tracer may hold a potential role as a noninvasive marker of glioma proliferative activity. Figure 1 T1-weighted, gadolinium-enchanced MRI (A) in a low-grade oligodendroglioma of the left frontal lobe. Faint 99mTc-Tetrofosmin uptake (B, arrow) correlated with Ki-67 approx. 2% (C; MIB-1 ×100). Figure 3 Correlation between 99mTc-Tetrofosmin uptake (expressed as lesion-to-normal [L/N] uptake ratio) and cellular proliferation rate (MIB-1) in the studied gliomas.

Prognostic evaluation of metallothionein expression in human colorectal neoplasms.

AIM: To investigate the role of metallothionein in colorectal tumours and the possible relation with other factors associated with tumour progression: expression of cathepsin D (CD), CD44, p53, Rb, bcl-2, c-erbB-2, epidermal growth factor receptor (EGFR), proliferation indices (Ki-67, proliferating cell nuclear antigen (PCNA)), and conventional clinicopathological variables. METHODS: The immunohistochemical expression of metallothionein was investigated in 23 cases of colorectal adenoma and 94 adenocarcinomas. Metallothionein expression was examined by the avidinbiotin peroxidase immunoperoxidase (ABC) using the monoclonal mouse antibody E9, on formalin fixed, paraffin embedded tissue. RESULTS: Positive metallothionein expression (> 5% of neoplastic cells) was observed in 30.4% of adenomas and 25.5% of adenocarcinomas, while 8.7% of adenomas and 14.9% carcinomas showed focal metallothionein positivity. In contrast, 60.9% of adenomas and 59.6% of carcinomas almost completely lacked metallothionein expression. In the series of adenocarcinomas, metallothionein expression was inversely correlated with CD44 in neoplastic cells (p = 0.01). There was no statistically significant difference of metallothionein expression, or the other variables examined, between adenocarcinomas and adenomas. CONCLUSIONS: Metallothionein expression does not seem to indicate aggressive biological behaviour in colorectal adenocarcinomas, in comparison with the other types of carcinoma. The inverse correlation with CD44 could suggest that the decreased metallothionein expression may contribute to the metastatic spread of the lymph node involvement in colorectal cancer. Metallothionein expression does not seem to represent an independent prognostic marker in colorectal cancer.

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.RésuméLes tumeurs desmoides sont des néoplasmes rares qui ont un caractère agressif local, mais aucune propension à métastaser. Elles sont principalement localisés dans la paroi abdominale, l’intestin et le mésentère et dans des sites extra-abdominaux tels que le tronc et les extrémités. La résection chirurgicale est la principale modalité du traitement pour les extrémités et le tronc avec la combinaison facultative de radiothérapie et/ou chimiothérapie. Cependant, ils ont une haute tendance à la récidive.

Descriptive Epidemiology of Cerebral Gliomas in Northwest Greece and Study of Potential Predisposing Factors, 2005–2007

Background: To investigate the epidemiologic and clinical characteristics (age, sex, tumor location, socioeconomic status) and potential predisposing factors (alcohol, tobacco, mobile phone use, severe head trauma) of cerebral gliomas in a defined area of Northwest Greece. Methods: The prospective study was conducted in patients with gliomas referred to all 7 hospitals of a study area with a population of 488,435 inhabitants, from June 1, 2005, to May 31, 2007. Incidence rates (IR) were calculated as new cases diagnosed among residents of the study area during the study period per 100,000 inhabitants. A case-control study was carried out in order to study the possible association of the risk of glioma with smoking, alcohol, use of mobile phone, and severe cranial trauma. Results: A total of 56 glioma incident cases were identified with IRs of glioma and glioblastoma (GBM) at 5.73/105/year and 3.69/105/year, respectively. A male to female ratio of 1.25 was obtained in the GBM group. IRs of glioma and GBM for both males and females were higher in the age group 60–79. The most frequent anatomic location was the frontal lobe. 46.5% of the patients originated from the low, 25% from the middle and 28.5% from the high socioeconomic class. There was no significant association between glioma and alcohol consumption, smoking and mobile phone use. A trend for a positive association between the risk of glioma and a history of severe cranial trauma was observed, but this association was not statistically significant. Conclusion: The estimated IR of glioma and GBM in this study was higher compared with data from other studies carried out on European, Asian and US populations. Further studies may be needed to assess the possible association of genetic, environmental and lifestyle factors with the high occurrence of gliomas observed in this study.

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.

Multi-focal gliosarcoma: a case report and review of the literature.

SummaryGliosarcoma (GS) is an uncommon malignant brain tumor with biphasic tissue pattern consisted of both glial and sarcomatous components. It usually occurs in adult population of middle age. We report a rare case of multi-focal GS that was initially interpreted as metastases of extra-cranial tumor. The histological examination revealed the biphasic pattern of a GS. The patient was treated with postoperative external radiation therapy and had poor prognosis. To our knowledge this is the second published case of GS with multi-focal presentation. In this study we also review the literature on clinicopathological aspects of GS.

Genetic abnormalities in oligodendroglial and ependymal tumours

Abstract Oligodendroglial and ependymal tumours are not the most common glial neoplasms; however, they are important subtypes of gliomas with different tumour biologies. Cytogenetic information has suggested that losses of chromosomes 1 p and 19 q are the most frequent genetic alterations in oligodendroglial tumours. Combined loss of these chromosomes has been associated with better chemotherapeutic response and prolonged overall survival. Loss of chromosome 22 is a well defined abnormality in ependymomas. In addition, deletion of chromosome 6 q may be another frequent chromosomic aberration in paediatric ependymomas.

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.

Expression of the extracellular matrix protein tenascin in laryngeal epithelial lesions: correlation with fibronectin, CD44, cathepsin D and proliferation indices

Abstract Tenascin (TN) is an extracellular matrix glycoprotein expressed in areas of epithelial–mesenchymal interactions during embryogenesis and in neoplasia. We studied the expression of TN in a series of 35 squamous cell invasive carcinomas of the larynx, 13 in situ car- cinomas, 41 cases of dysplasia, 10 papillomas and 18 cases of keratosis using the monoclonal antibody TN2 on paraffin-embedded tissue. TN expression was correlated with the expression of fibronectin, CD44 and cathepsin D (CD) proteins, with the proliferation indices Ki-67 and proliferating cell nuclear antigen (PCNA) as well as with conventional clinicopathological variables. Malignant tumours showed a significantly greater stromal TN staining than benign lesions. In invasive carcinomas, the immunoreactivity was statistically higher than that in situ (P=0.01), dysplastic lesions (P<0.0001), papillomas (P=0.004) and keratosis (P<0.0001). A statistically significant difference of TN expression between in situ and dysplastic lesions was observed (P=0.001). In invasive lesions, TN expression was statistically correlated with CD44 expression (P=0.02) and a trend for correlation with CD of tumour cells and fibronectin expression was found (P=0.06 and P=0.09, respectively). The relationship of TN expression with the histological grade and the proliferative activity was insignificant. In conclusion, stromal TN expression may be involved in the complex mechanism of development of laryngeal lesions and may help to predict the risk of progression of pre-cancerous lesions to cancer.

Non‐invasive assessment of meningioma Ki‐67 proliferative index by 99mTc‐Tetrofosmin brain scintigraphy

With great interest we read a recent article on atypical and anaplastic meningiomas by Bruna et al. investigating the clinical and prognostic significance of their proliferative profile, as expressed by the Ki-67 index. The authors studied 28 cases of meningioma and found by both univariate and multivariate analysis that the Ki-67 proliferative index was the strongest predictor of tumor recurrence and overall patient survival. A cut-off threshold value of Ki-67 = 9.9% best separated lesions with favorable from those with non-favorable outcome. More importantly, the authors reported that the proliferative index maintained its discriminating value in both atypical and anaplastic lesions, thus contributing to refining the current World Health Organization classification and better predicting clinical outcome and prognosis. These results substantially support our ongoing in vivo imaging studies on meningiomas and other intracranial tumors by single-photon emission computed tomography (SPECT), a nuclear medicine functional imaging technique. We are currently investigating the brain tumor imaging properties of technetium-99m-Tetrofosmin (TcTF), a lipophilic diphosphine routinely used for myocardial perfusion imaging that also displays tumor-seeking properties. We showed that Tc-TF SPECT can reliably distinguish glioma recurrence from radiation necrosis and neoplastic from non-neoplastic intracranial hemorrhage. Furthermore, we evaluated the relationship between glioma proliferation (as expressed by Ki-67) and the uptake of Tc-TF and verified a strong positive linear correlation between tracer uptake and Ki-67 expression. To substantiate a possible analogous correlation between Tc-TF uptake and cellular proliferation in meningiomas,we prospectively evaluated 15 cases,12 typical and three anaplastic. Brain SPECT by Tc-TF was performed within a week prior to surgical excision and the tumoral radiotracer uptake was assessed visually and semiquantitatively (calculation of the lesion-to-normal uptake ratio, as described elsewhere). In the excised tumor specimens we then assessed Ki-67 antigen expression by the MIB-1 Fig. 1 (A) T1-weighed, gadolinium-enchanced MRI demonstrating a meningioma. (B) Tc-Tetrofosmin brain single-photon emission computed tomography showing profound radiotracer accumulation in the same region as shown on MRI. Histopathology verified the presence of an anaplastic meningioma. The Ki-67 index was ~20%. Neuropathology 2008; 28, 106–107 doi:10.1111/j.1440-1789.2007.00848.x