WHO Tumor Grade Research Articles

Quantitative methylation analysis of HOXA3, 7, 9, and 10 genes in glioma: association with tumor WHO grade and clinical outcome

The purpose of this study was to determine whether specific HOXA epigenetic signatures could differentiate glioma with distinct biological, pathological, and clinical characteristics. We evaluated HOXA3, 7, 9, and 10 methylation in 63 glioma samples by MassARRAY and pyrosequencing. We demonstrated the direct statistical correlation between the level of methylation of all HOXA genes examined and WHO grading. Moreover, in glioblastoma patients, higher level of HOXA9 and HOXA10 methylation significantly correlated with increased survival probability (HOXA9-HR: 0.36, P=0.007; HOXA10-HR: 0.46, P=0.045; combined HOXA9 and 10-HR 0.28, P=0.004). This study identifies HOXA3, 7, 9, and 10 as methylation targets mainly in high-grade glioma and hypermethylation of the HOXA9 and 10 as prognostic factor in glioblastoma patients. Our data indicate that these epigenetic changes may be biomarkers of clinically different subgroups of glioma patients that could eventually benefit from personalized therapeutic strategies.

Decreased RECK and Increased EMMPRIN Expression in Urothelial Carcinoma of the Bladder Are Associated with Tumor Aggressiveness

Objective: Urothelial bladder carcinomas show a divergent biological behavior, which significantly complicates risk stratification and clinical management. The MMP repressor RECK and the MMP activator EMMPRIN regulate the invasive potential by metalloproteinase-induced stromal degradation. Data on RECK in urothelial bladder cancer are lacking and information on EMMPRIN is sparse. This study aims to investigate the expression of RECK and EMMPRIN in urothelial carcinoma of the bladder and to correlate these findings with clinicopathological parameters. Methods: Our study included 127 specimens of urothelial carcinomas derived from 103 patients who underwent either TUR-B or cystectomy. Immunohistochemical expression analysis was performed for RECK, EMMPRIN, MMP-2, MMP-9 and MMP-14. Expression levels were graded for staining intensity and correlated with pT stage and WHO tumor grade. Results: Invasive (≧pT1) as well as WHO high-grade urothelial carcinomas showed a statistically significant and stepwise downregulation of RECK (p < 0.001) and concomitant upregulation of EMMPRIN (p < 0.001) compared to non-invasive and WHO low-grade tumors. No correlation was observed for the MMPs investigated. Conclusion: Decreased RECK and increased EMMPRIN expression are associated with increasing stage and grade. Both proteins may serve as molecular marker for the distinction between potentially invasive (≧pT1) and non-invasive tumors (≤pTa).

Childhood Tumors of the Brain: Demographic Pattern over a Ten-Year Period in the Kashmir Valley

Brain tumors in children represent the second most frequent tumors in this age group after hematologic malignancies. We highlight the demographic pattern after retrospective analysis of brain tumors in children from geographically and ethnically distinct Kashmir Valley managed in our center between 2000 and 2009. We had a total of 248 pediatric patients with brain tumors. The parameters analyzed were age, gender, location of tumors and histopathological subtypes as well as WHO grade of tumor. We also did a comparison between the frequencies of common varieties of tumor in the first and second 5-year periods. We found that 111 tumors (44.75%) were supratentorial, and 137 (55.25%) were infratentorial. The male-to-female ratio was 1.4:1. The proportions of low-grade and high-grade tumors were 60 and 40%, respectively. The most common tumor in our series was astrocytoma. The most common tumors in the supratentorial and infratentorial compartments were craniopharyngioma and medulloblastoma, respectively. Our experience reflects a different demographic profile of pediatric brain tumors as compared with other regions of the world.

Postoperative seizures following the resection of convexity meningiomas: are prophylactic anticonvulsants indicated?

Seizures in the perioperative period are a well-recognized clinical entity in the setting of brain tumor surgery. At present, the suitability of antiepileptic prophylaxis in patients following brain tumor surgery is unclear, especially in those without prior seizures. Given the paucity of tumor-type and site-specific data, the authors evaluated the incidence of postoperative seizures in patients with convexity meningiomas and no prior seizures. The authors identified 180 patients with no preoperative history of seizures who underwent resection of a convexity meningioma. Some patients received antiepileptic prophylaxis for 7 days postoperatively while others did not, based on the practice patterns of different attendings. The rates of clinically evident seizures in the first 3-4 weeks after surgery were compared. Patients who received antiepilepsy drugs (129 patients) did not significantly differ from those who did not (51 patients) in terms of age, sex, WHO tumor grade, extent of resection, rate of previous cranial surgery or radiation therapies, or use of preoperative embolization. There was a single new postoperative seizure in the entire cohort, yielding a new seizure rate of 1.9% in patients not on antiepileptic prophylaxis compared with 0% in patients on antiepileptics (p = not significant). While it is thought that the routine use of prophylactic antiepileptics may prevent new seizures in patients undergoing surgery for a convexity meningioma, the rate of new seizures in untreated patients is probably very low. Data in this study call into question whether the cost and side effects of these medications are worth the small benefit their administration may confer.

Micro-RNA-128 (miRNA-128) down-regulation in glioblastoma targets ARP5 (ANGPTL6), Bmi-1 and E2F-3a, key regulators of brain cell proliferation

High density micro-RNA (miRNA) arrays, fluorescent-reporter miRNA assay and Northern miRNA dot-blot analysis show that a brain-enriched miRNA-128 is significantly down-regulated in glioblastoma multiforme (GBM) and in GBM cell lines when compared to age-matched controls. The down-regulation of miRNA-128 was found to inversely correlate with WHO tumor grade. Three bioinformatics-verified miRNA-128 targets, angiopoietin-related growth factor protein 5 (ARP5; ANGPTL6), a transcription suppressor that promotes stem cell renewal and inhibits the expression of known tumor suppressor genes involved in senescence and differentiation, Bmi-1, and a transcription factor critical for the control of cell-cycle progression, E2F-3a, were found to be up-regulated. Addition of exogenous miRNA-128 to CRL-1690 and CRL-2610 GBM cell lines (a) restored 'homeostatic' ARP5 (ANGPTL6), Bmi-1 and E2F-3a expression, and (b) significantly decreased the proliferation of CRL-1690 and CRL-2610 cell lines. Our data suggests that down-regulation of miRNA-128 may contribute to glioma and GBM, in part, by coordinately up-regulating ARP5 (ANGPTL6), Bmi-1 and E2F-3a, resulting in the proliferation of undifferentiated GBM cells.

Snail and Cox-2 expressions are associated with WHO tumor grade and survival rate of patients with gliomas

The transcriptional factor Snail and enzyme cyclo-oxygenase-2 (Cox-2) are suggested to be important effectors of invasiveness and tumorigenesis in various tumors. Tumors of higher grade have the propensity for tumor cell migration and invasiveness. This study was performed in order to evaluate the association between Snail and Cox-2 expressions and their values as prognostic factors in various grades of glioma, Specimens of 56 patients with glioma were used in the study. Univariate analysis showed that WHO tumor grade, and expressions of Snail and Cox-2 were significant prognostic factors affecting overall and disease progression-free survival rates. In the multivariate analysis by Cox regression model, only WHO tumor grade was shown to be a significant independent prognostic factor of overall and progression-free survival rates. In conclusion, Snail and Cox-2 expressions were associated with WHO grade in gliomas and may be used as prognostic indicators.

A closer look at the number of lymph nodes examined in colorectal cancer: A VAMC experience

e15117 Background: Retrieval of 12 lymph nodes (LN) is a current benchmark in colorectal cancer (CRC) resections according to the National Quality Forum (NQF). Series of multiple institutions contain variability in surgical and pathologic techniques for lymph node retrieval. To ensure consistency in retrieving lymph nodes for satisfactory staging, we present a 12 year experience by a single surgeon and single pathology lab at one VAMC on 157 patients (mean age 67) undergoing CRC resection. Furthermore, the use of chemotherapy for Stage II patients &lt;12 LN retrieved is controversial and yields only a small survival benefit. Methods: The records of 157 patients from one surgeon's case log from 1994–2007 were reviewed. Strict guidelines were applied to remove the same distribution of pericolonic fat. The lab followed a two step approach to LN dissection: Step 1 search for grossly identifiable LN; Step 2 overnight Carnoy's immersion to find smaller LN. Statview and SAS software analyzed 1)Overall survival (OS) and association with finding &gt;12LN; 2)Number of LN identified and impact on AJCC tumor stage (TS) and overall survival; 3)Number of LN and WHO tumor grade (TG) with OS; 4)The impact of number of positive LN on OS. Results: Our mean LN found (14.75) is higher than the 12 recommended by the NQF and is not significantly associated with OS regardless of AJCC TS(p=0.06). The mean LN per TS was I=13.4(N=41)/II=16.3(N=56)/ III=14.3(N=38)/IV 14.2(N=22). Number of LN identified was not statistically significant in predicting TS(p=0.42) or OS(p=0.24). WHO TG is significantly associated to decreased OS, but only in AJCC TS II/III/IV and not stage I (Ip&gt;0.05/IIp=0.008/ IIIp=0.01/IVp=0.025). Higher number of positive LN was associated with lower OS (per each +LN, survival decreases by 0.15 months p=0.001) Conclusions: Contrary to multicenter studies, total number of LN identified does not impact AJCC TS or OS. Higher WHO TG and higher number of positive LN is associated with worse OS. This suggests that the tumor biology is more indicative of OS rather than host response (reactive lymphoid tissue) to the tumor. Stage II patients &lt;12 LN may not be ‘high risk’ and adjuvant chemotherapy based on this factor alone should be reconsidered. Further studies would be warranted. No significant financial relationships to disclose.

Retrospective analysis: Patients with ovarian cancer at National Cancer Institute of Mexico

e16573 Background: Ephitelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies among women worldwide. Little is known about reproductive factors or lifestyle determinants and ovarian cancer prognosis. The purpose of this study was to analyze the pathologic, clinical and other characteristics. Methods: This study included all EOC seen at the Institute from 2000–2006. Epidemiological and clinical variables were collected from the patients’ medical records. Exposure data on prediagnostic factors were collected through questionnaires. The cases were followed-up until December 31, 2007. Cox proportional hazard regression model was used to estimate the prognostic effect of each factor in terms of hazard ratios (HR) and 95% confidence intervals (CI), following adjustment for age at diagnosis, FIGO tumor stage and WHO grade of tumor differentiation. Results: 571 cases of ovarian cancers. Median age was 51 years, (range 18–95). 20.30%, 4.4%, and 63.5% of patients had stage I, II and III, respectively. The histological types: 52.2% serous, 17.2% endometrioid, 12.8% of mucinous origin; 62.5% underwent radical surgery, 24% with optimal cytorreduction. The mean follow-up was 60 ± 22 months. The overall three-year survival was 97.4% and 98% for mucinous and serous tumors, respectively. The survival rate was 100%, 90%, and 71.8% in stages I, II and III, respectively. After adjustment for the tumor characteristics, no clear associations were detected between reproductive history, anthropometric characteristics, factors before diagnosis (alcohol consumption, smoking and physical activity over lifetime), nor family history of breast cancer or ovarian cancer and survival Conclusions: Our findings indicate that the tumor characteristics significantly influenced the risk of death from ovarian cancer and no clear associations were detected between others factors and the survival. In this cohort the median age for ovarian cancer were 51 years old, one decade before than other reports. No significant financial relationships to disclose.

Outcomes of Malignant CNS Ependymomas: An Examination of 2408 Cases Through the Surveillance, Epidemiology, and End Results (SEER) Database (1973–2005)

Determine the role of surgery and radiation therapy for patients with malignant CNS ependymomas. The Surveillance, Epidemiology, and End Results (SEER) database (1973-2005) was queried. Overall, a total of 2408 cases of malignant ependymomas were identified. Of these, 2132 cases (88.5%) were identified as WHO grade II ependymomas and 276 cases (11.5%) as WHO grade III (anaplastic) ependymomas. The annual incidence of ependymomas was approximately 1.97 cases per million in 2005. Overall median survival for all patients was 230 mo, with a significant difference between women and men (262 mo versus196 mo, respectively) (P=0.004). Median age at diagnosis was 37 y among females and 34 y in males. Patients who successfully underwent surgical resection had a considerably longer median survival (237 mo versus 215 mo, P<0.001) as well as a significantly improved five-year survival (72.4% versus 52.6%, P<0.001). Univariate analysis demonstrated that age, gender, ethnicity, primary tumor site, WHO grade and surgical resection were significant predictors of improved survival for ependymoma patients. Multivariate analysis identified that a WHO grade III tumor, male gender, patient age, intracranial tumor locations and failure to undergo surgical resection were independent predictors of poorer outcomes. Multivariate analysis of partially resection cases revealed that lack of radiation was a sign of poor prognosis (HR 1.748, P=0.024). Surgical extirpation of ependymomas is associated with significantly improved patient survival. For partially resected tumors, radiation therapy provides significant survival benefit.

Glioma vascularity correlates with reduced patient survival and increased malignancy

Background The objective of this study was 2-fold: (1) document the presence and degree of vascularity in gliomas of different pathologic grades and (2) determine whether the presence of abnormal vascularity, determined by catheter angiography, correlates with a shortened survival. Methods As part of a protocol for radiographic data acquisition that was used in a computer-assisted, stereotactic system, all patients who underwent biopsy or resection of a newly diagnosed glioma between 1994 and 2000 at our institution routinely underwent preoperative catheter angiography. The presence and degree of tumor vascularity were recorded and then correlated with survival and pathologic grade. The confounding effects of age, KPS, adjuvant treatment, and extent of resection on survival were considered. Results Two hundred thirty-one patients were included in this study. The mean follow-up of survivors was 7.8 years. Tumor vascularity correlated with a shortened survival (proportional hazards RR for survival, 0.69; 95% CI, 0.58-0.82). This correlation persisted after correction for age, KPS score, adjuvant therapy, and extent of resection (RR, 0.81; 95% CI, 0.68-0.97). Abnormal vascularity was present in 25 (30%) of 82 low-grade (WHO grade 2) gliomas. Overall, the extent of vascularity (none [120 patients, 52%], blush [63 patients, 27%], neovessels [25 patients, 11%], and arteriovenous shunting [23 patients, 10%]) correlated with worse WHO tumor grade (P < .0001). Conclusions The presence of abnormal vascularity correlates with both a shortened survival and higher grade of malignancy. These findings underscore the importance of antiangiogenesis factor investigation and drug development for the treatment of gliomas, regardless of their pathologic grade.

Expression of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins in human ependymoma relates to tumor location, WHO Grade, and patient age

Three human leucine-rich repeats and immunoglobulin-like domains (LRIG1-3) genes and proteins have recently been characterized. LRIG1 has been shown to be a suppressor of tumor growth by counteracting the signaling of epidermal growth factor receptor (EGFR) family members, including EGFR (ERBB1). Expression of LRIG proteins seems to be of importance in the pathogenesis of astrocytic tumors. In this study, the expression of LRIG1-3 was evaluated in 51 human ependymomas by immunohistochemistry. LRIG proteins were detected in all ependymomas analyzed, however, with a pronounced heterogeneity in expression and subcellular localization. Higher cytoplasmic immunoreactivity of LRIG1 correlated with older patient age and higher LRIG1 nuclear immunoreactivity with lower WHO Grade. LRIG1 displayed a stronger immunoreactivity in the cytoplasm and nuclei in spinal ependymomas than in the posterior fossa or supratentorial ependymomas, while perinuclear LRIG3 was more highly expressed in supratentorial than in infratentorial ependymomas. The indications that expression and subcellular localization of LRIG proteins could be pathogenetically associated with specific clinicopathological features of ependymoma tumors might be of importance in the carcinogeneses and tumor progression of human ependymomas.

Predictors of ovarian cancer survival: A population‐based prospective study in Sweden

Ovarian cancer is the leading cause of death from gynecologic malignancies among women worldwide. Little is known about reproductive factors or lifestyle determinants and ovarian cancer prognosis. The objective of this study was to examine whether ovarian cancer survival is influenced by reproductive history, anthropometric characteristics, prediagnostic life-style factors and family history of breast or ovarian cancer. The study population consisted of 635 epithelial ovarian cancer (EOC) cases derived from a nationwide population-based case-control study conducted in Sweden between 1993 and 1995. Exposure data on prediagnostic factors of interest were collected through questionnaires at the beginning of the parent study. Clinical data were abstracted from medical records. Cases were followed-up by means of record linkage to nationwide registers until December 31, 2002. Cox proportional hazard regression model was used to estimate the prognostic effect of each factor in terms of hazard ratios (HR) and 95% confidence intervals (CI), following adjustment for age at diagnosis, FIGO tumor stage and WHO grade of tumor differentiation. Tumor characteristics significantly influenced the risk of death from EOC. After adjustment for these, no clear associations were detected between reproductive history (parity, age at first or last birth, oral contraceptive use, age at menarche or menopause), anthropometric characteristics (body size and shape in different periods of life), lifestyle factors before diagnosis (alcohol consumption, smoking and physical activity over lifetime), nor family history of breast cancer or ovarian cancer and EOC survival. Our findings indicate that these prediagnostic factors do not influence the EOC survival. Nevertheless, among women with early stage disease (FIGO stage I and II), there was some indication that overweight in young adulthood or recent years increased the risk of death, while physical activity in young adult life appeared to reduce the risk of death due to EOC.

Evaluation and characterization of generalized anxiety and depression in patients with primary brain tumors

To determine clinical and sociodemographic factors that are associated with major neuropsychiatric illnesses among brain tumor patients, we administered a modified version of the Brief Patient Health Questionnaire and a demographic data form to 363 adult neuro-oncology patients. Responses were analyzed to assess for associations between demographic variables, clinical variables, and symptoms consistent with diagnoses of generalized anxiety disorder and/or depression. Multivariate logistic regression analyses showed that female gender was associated with the presence of symptoms of anxiety, depression, and combined anxiety and depression. Lower WHO tumor grade classifications, lower education level, and a history of psychiatric illness also emerged as important predictors of symptoms consistent with anxiety and/or depression. Marital status and presence of past/current medical illness trended toward being significantly associated with depression alone. Patient use of psychiatric medication was not associated with any study variables. Results of the present study suggest several hypotheses to test with neuro-oncology patients in further longitudinal analyses, which would benefit from the inclusion of a wider range of neuropsychiatric symptoms in conjunction with neurocognitive and functional impairment variables.

Changes of Biochemical Markers of Bone Turnover and YKL-40 Following Hormonal Treatment for Metastatic Prostate Cancer Are Related to Survival

Elevated serum levels of biochemical markers of bone turnover and YKL-40 in patients with metastatic prostate cancer (PC) at the time of diagnosis are associated to poor prognosis. In this study, we evaluated the value of these biomarkers in monitoring the patients during hormonal treatment. Serum procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (BAP), CTX-I, and YKL-40 were determined by ELISA in a longitudinal study of 106 patients with metastatic PC during treatment with total androgen ablation or parenteral estrogen. Serum samples were collected with 3 months interval. Median observation time was 4.9 years (range, 3.6-6.2). A total of 78 patients died (64 within 7 months following the last blood sampling). After 6 months treatment, serum PINP, BAP, and YKL-40 decreased (P < 0.0001), but not serum CTX-I compared with baseline values. Univariate Cox analysis showed that serum PINP at 6 months [log transformed and treated as a continuous variable; hazard ratio (HR), 2.2; P < 0.0001], serum BAP (HR, 1.8; P < 0.0001), and serum CTX-I (HR, 2.4; P < 0.0001), but not serum YKL-40 (HR, 1.4; P = 0.16) were associated with survival. Multivariate Cox analysis including the biomarkers 6 months after the start of treatment showed that Soloway score (HR, 3.9; P = 0.013), WHO tumor grade (HR, 3.9; P = 0.004), and serum PINP (HR, 2.2; P < 0.0001) were independent prognostic variables of survival. Scoring the biomarkers during treatment as time-dependent covariates in univariate Cox regression analysis showed that increases in serum PINP (HR, 2.0; P < 0.0001), BAP (HR, 2.1; P < 0.0001), and YKL-40 (HR, 2.1; P < 0.0001) were predictors of early death. Serial monitoring of serum PINP, BAP, CTX-I, and YKL-40 in metastatic PC patients during hormonal treatment provided information of prognosis.

Expression of interleukin-13 receptor and its relationship to proliferation activity of human gliomas

目的 探讨人脑胶质瘤白介素13受体(IL-13R)基因表达与肿瘤增殖活性的关系.方法 对6例正常脑组织,50例人脑胶质瘤和2个脑瘤体外细胞系采用RT-PCR法和免疫组织化学法检测IL-13R.结果 人脑胶质瘤组织IL-13RαmRNA总阳性表达率70%,正常脑组织中仅1例有极弱的表达;2例恶性胶质瘤体外细胞系均高表达.IL-13RαmRNA表达率和表达丰度与胶质瘤分级(前者rs=0.87,P＜0.01;后者rs=0.69,P＜0.01)、肿瘤增殖活性Ki-67LI(r=0.64,P＜0.01)呈正相关,即胶质瘤恶性程度越高,IL-13RαmRNA表达率和表达水平越高.结论 IL-13Rα基因在人脑胶质瘤中表达上升,与肿瘤的分级和肿瘤增殖活性呈正相关,可作为预测某些肿瘤治疗效果及监测复发的指标之一。

Precystectomy Nomogram for Prediction of Advanced Bladder Cancer Stage

ObjectiveTo evaluate precystectomy prediction of pT and pN stages at cystectomy. MethodsMultivariate logistic regression analyses modelled variables of 726 evaluable patients treated with radical cystectomy and bilateral pelvic lymphadenectomy. The first set of models predicted pT3–4 stage at cystectomy, and the second set predicted pN1–3 stages at cystectomy. Transurethral resection (TUR) predictors consisted of 2002 T stage, 1973 WHO tumour grade, presence of carcinoma in situ, age, gender, and delivery of neo-adjuvant chemotherapy. The area under the ROC curve quantified nomogram accuracy. Two hundred bootstrap resamples were used to reduce overfit bias. ResultsAt TUR, 11% of patients were staged as pT3–4 versus 42% at cystectomy. Lymph node metastases were found in 24% of patients at cystectomy (pN1–3). The multivariate pT3–4 nomogram was 75.7% accurate versus 71.4% for TUR T stage. The multivariate pN1–3 nomogram was 63.1% accurate versus 61.0% for TUR T stage. ConclusionMultivariate nomograms are not perfect, but they do predict more accurately than TUR T stage alone.

Metalloproteinase Disintegrins ADAM8 and ADAM19 Are Highly Regulated in Human Primary Brain Tumors and their Expression Levels and Activities Are Associated with Invasiveness

Patients with primary brain tumors have bleak prognoses and there is an urgent desire to identify new markers for sensitive diagnosis and new therapeutic targets for effective treatment. A family of proteins, the disintegrin and metalloproteinases (ADAMs or adamalysins), are cell surface and extracellular multidomain proteins implicated in cell-cell signaling, cell adhesion, and cell migration. Their putative biological and pathological roles make them candidates for promoting tumor growth and malignancy. We investigated the expression levels of 12 cerebrally expressed ADAM genes in human primary brain tumors (astrocytoma WHO grade I-III, glioblastoma WHO grade IV, oligoastrocytoma WHO grade II and III, oligodendroglioma WHO grade II and III, ependymoma WHO grade II and III, and primitive neuroectodermal tumor WHO grade IV) using real-time PCR. The mRNAs of the five ADAMs 8, 12, 15, 17, and 19 were significantly upregulated. The ADAM8 and ADAM19 proteins were mainly located in tumor cells and in some tumors in endothelia of blood vessels. In brain tumor tissue, ADAM8 and ADAM19 undergo activation by prodomain removal resulting in active proteases. By using specific peptide substrates for ADAM8 and ADAM19, respectively, we demonstrated that the proteases exert enhanced proteolytic activity in those tumor specimens with the highest expression levels. In addition, expression levels and the protease activities of ADAM8 and ADAM19 correlated with invasive activity of glioma cells, indicating that ADAM8 and ADAM19 may play a significant role in tumor invasion that may be detrimental to patients survival.

Prognostic value of PINP, bone alkaline phosphatase, CTX‐I, and YKL‐40 in patients with metastatic prostate carcinoma

To examine the prognostic value of markers of bone metabolism (serum PINP, BAP, and CTX-I) and serum YKL-40 in metastatic prostate carcinoma (PC). The biomarkers were determined by ELISAs in 153 metastatic PC patients before treatment with parenteral estrogen or total androgen ablation. The median follow-up was 4.9 years. One hundred fifteen patients died. The biomarkers were increased in the patients compared to controls (P < 0.001), and related to performance status and Soloway score (except YKL-40), but not to T-category and WHO tumor grade. PINP was elevated in 87%, BAP (55%), CTX-I (33%), and YKL-40 (43%). Univariate analysis showed an association to survival: PINP (HR = 1.6, P < 0.0001), BAP (HR = 1.4, P < 0.0001), CTX-I (HR = 1.7, P < 0.0001), and YKL-40 (HR = 1.4, P = 0.004). In multivariate Cox analysis performance status, WHO grade, Soloway score, PINP, and YKL-40 were independently predictive factors. High serum PINP, BAP, CTX-I, and YKL-40 are associated with poor outcome of metastatic PC patients.

Detection and differentiation of lactate and lipids by single-voxel proton MR spectroscopy

The signals of lactate and lipids partially overlap in single-voxel proton MR spectroscopy (1HMRS), sometimes making them difficult to differentiate in clinical settings. Our aim in this study was to identify lactate and lipids by varying the echo time (TE). We expect that the accurate detection of lactate and lipids will have high diagnostic value in the diagnosis of brain tumors. Following our protocol, we obtained meaningful 1HMRS spectra from 213 patients, including 163 patients with brain tumors, between August 1999 and February 2004. 1HMRS was performed with a TE of 144 ms followed by a TE of 30 ms and/or a TE of 288 ms, if necessary. For the 213 patients, lactate level was "negative" in 47 patients, "positive" in 131 patients, and "strongly positive" in 35 patients. The lipid level was "negative" in 90 patients, "positive" in 56 patients, and "strongly positive" in 67 patients. Based on logistic discriminant analyses of neuro-epithelial tumor WHO grade and lactate and lipid levels, lactate and lipid levels were significant between WHO grades 2 and 3 (P=0.0239) and between grades 3 and 4 (P=0.0347). Lipids are a more significant factor for the discrimination between WHO grades 2 and 3 (P=0.0073) and between grades 3 and 4 (P=0.0048). With our method of varying the TE, it is possible accurately and efficiently to detect lactate and lipids in the brain. We found a significant correlation between lactate and lipid expression and WHO grade of neuro-epithelial tumors.

Ezrin expression in tissue microarray of primary and recurrent gliomas.

Malignant progression, infiltrative growth pattern and recurrencies after surgery are characteristic features of diffuse gliomas. Ezrin is a membrane-cytoskeleton linker protein expressed in several types of neoplasms. In experimental models, increased ezrin expression correlates with invasion of malignant glioma cells. We studied ezrin expression and its correlation with patient survival in 229 primary and recurrent astrocytomas (WHO grades II-IV), oligodendrogliomas (II-III) and oligoastrocytomas (II-III) of 113 patients. Ezrin expression as evaluated by immunohistochemistry and immunoblotting was detected in all studied glioma types. Staining intensity and number of immunoreactive cells correlated with increasing malignancy of astrocytomas and oligoastrocytomas (P = 0.001). Ezrin expression was strongest in astrocytomas (P = 0.006). Also oligodendrogliomas were positive for ezrin. High ezrin expression in primary gliomas correlated with shorter time to recurrence (P < 0.05) and poor overall survival (P < 0.05) of the patients. Ezrin expression increased during progression of the tumours (P < 0.05). However, ezrin was not an independent prognostic factor. The results of this study show that ezrin expression is associated with progression of gliomas and correlates with histological cell type and WHO tumour grade.