Papillary Tumor of the Pineal Region: A Distinct Molecular Entity.

Papillary tumor of the pineal region (PTPR) is a neuroepithelial brain tumor, which might pose diagnostic difficulties and recurs often. Little is known about underlying molecular alterations. We therefore investigated chromosomal copy number alterations, DNA methylation patterns and mRNA expression profiles in a series of 24 PTPRs. Losses of chromosome 10 were identified in all 13 PTPRs examined. Losses of chromosomes 3 and 22q (54%) as well as gains of chromosomes 8p (62%) and 12 (46%) were also common. DNA methylation profiling using Illumina 450k arrays reliably distinguished PTPR from ependymomas and pineal parenchymal tumors of intermediate differentiation. PTPR could be divided into two subgroups based on methylation pattern, PTPR group 2 showing higher global methylation and a tendency toward shorter progression-free survival (P = 0.06). Genes overexpressed in PTPR as compared with ependymal tumors included SPDEF, known to be expressed in the rodent subcommissural organ. Notable SPDEF protein expression was encountered in 15/19 PTPRs as compared with only 2/36 ependymal tumors, 2/19 choroid plexus tumors and 0/23 samples of other central nervous system (CNS) tumor entities. In conclusion, PTPRs show typical chromosomal alterations as well as distinct DNA methylation and expression profiles, which might serve as useful diagnostic tools.

Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma.

Astrocytoma and oligodendroglioma are histologically and genetically well-defined entities. The majority of astrocytomas harbor concurrent TP53 and ATRX mutations, while most oligodendrogliomas carry the 1p/19q co-deletion. Both entities share high frequencies of IDH mutations. In contrast, oligoastrocytomas (OA) appear less clearly defined and, therefore, there is an ongoing debate whether these tumors indeed constitute an entity or whether they represent a mixed bag containing both astrocytomas and oligodendrogliomas. We investigated 43 OA diagnosed in different institutions employing histology, immunohistochemistry and in situ hybridization addressing surrogates for the molecular genetic markers IDH1R132H, TP53, ATRX and 1p/19q loss. In all but one OA the combination of nuclear p53 accumulation and ATRX loss was mutually exclusive with 1p/19q co-deletion. In 31/43 OA, only alterations typical for oligodendroglioma were observed, while in 11/43 OA, only indicators for mutations typical for astrocytomas were detected. A single case exhibited a distinct pattern, nuclear expression of p53, ATRX loss, IDH1 mutation and partial 1p/19q loss. However, this was the only patient undergoing radiotherapy prior to surgery, possibly contributing to the acquisition of this uncommon combination. In OA with oligodendroglioma typical alterations, the portions corresponding to astrocytic part were determined as reactive, while in OA with astrocytoma typical alterations the portions corresponding to oligodendroglial differentiation were neoplastic. These data provide strong evidence against the existence of an independent OA entity.

Increased mitotic and proliferative activity are associated with worse prognosis in papillary tumors of the pineal region.

Papillary tumors of the pineal region are rare glial tumors located in the vicinity of the third ventricle, the clinical behavior of which is often aggressive. Little is known about the prognostic markers that might aid to identify patients at increased risk for recurrence. Therefore, the prognostic value of histopathologic and clinical features was examined in a series of 21 patients. Median age of the 12 male and 9 female patients was 35 years (range, 10 to 56 y). On histopathologic examination, all tumors were characterized by loose papillary structures and tumor cells forming broad perivascular pseudorosettes showing cytokeratin expression. In addition, tumors showed increased cellularity (n=4; 19%), nuclear pleomorphism (n=4; 19%), solid growth (n=11; 52%), necrosis (n=8; 38%), increased mitotic activity (≥3 mitoses per 10 high-power fields [n=10; 48%]), and increased proliferation (Ki67/MIB1 index ≥10% [n=8/20; 40%]). Gross total resection could be achieved in 13/21 patients (62%). Postoperatively, 13 patients received radiotherapy and 4 patients chemotherapy. Median recurrence-free survival was 66 months in 19 patients, for whom detailed follow-up information was available. Twelve patients (63%) experienced tumor progression. Three patients (16%) died of disease. Among the clinical and histopathologic features examined, only increased mitotic activity (52 [8 to 96] vs. 68 [66 to 70] mo [median [95% confidence interval]]) and proliferative activity (29 [0 to 64] vs. 67 [44 to 90] mo) were significantly associated with recurrence (P<0.05). Tumors of the 3 patients who had succumbed to disease showed increased mitotic and proliferative activity. In conclusion, increased mitotic and proliferative activities are associated with worse prognosis in papillary tumors of the pineal region.

AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry.

The activating E17K mutation in the AKT1 gene has been detected in several tumor entities. Currently several clinical studies with specific AKT1 inhibitors are under way. To determine whether AKT1 mutations are involved in human tumors of the nervous system, we examined a series of 1,437 tumors including 391 primary intracranial brain tumors and 1,046 tumors of the coverings of the central and peripheral nervous system. AKT1E17K mutations were exclusively seen in meningiomas and occurred in 65 of 958 of these tumors. A strong preponderance was seen in the variant of meningothelial meningioma WHO grade I of basal and spinal localization. In contrast, AKT1E17K mutations were rare in WHO grade II and absent in WHO grade III meningiomas. In order to more effectively detect this mutation, we tested for immunohistochemical markers associated with this alteration. We observed strong up-regulation of SFRP1 expression in all meningiomas with AKT1E17K mutation and in HEK293 cells after transfection with mutant AKT1E17K, but not in meningiomas and HEK293 cells lacking this mutation.

Meningeal hemangiopericytoma and solitary fibrous tumors carry the NAB2-STAT6 fusion and can be diagnosed by nuclear expression of STAT6 protein.

Non-central nervous system hemangiopericytoma (HPC) and solitary fibrous tumor (SFT) are considered by pathologists as two variants of a single tumor entity now subsumed under the entity SFT. Recent detection of frequent NAB2-STAT6 fusions in both, HPC and SFT, provided additional support for this view. On the other hand, current neuropathological practice still distinguishes between HPC and SFT. The present study set out to identify genes involved in the formation of meningeal HPC. We performed exome sequencing and detected the NAB2-STAT6 fusion in DNA of 8/10 meningeal HPC thereby providing evidence of close relationship of these tumors with peripheral SFT. Due to the considerable effort required for exome sequencing, we sought to explore surrogate markers for the NAB2-STAT6 fusion protein. We adopted the Duolink proximity ligation assay and demonstrated the presence of NAB2-STAT6 fusion protein in 17/17 HPC and the absence in 15/15 meningiomas. More practical, presence of the NAB2-STAT6 fusion protein resulted in a strong nuclear signal in STAT6 immunohistochemistry. The nuclear reallocation of STAT6 was detected in 35/37 meningeal HPC and 25/25 meningeal SFT but not in 87 meningiomas representing the most important differential diagnosis. Tissues not harboring the NAB2-STAT6 fusion protein presented with nuclear expression of NAB2 and cytoplasmic expression of STAT6 proteins. In conclusion, we provide strong evidence for meningeal HPC and SFT to constitute variants of a single entity which is defined by NAB2-STAT6 fusion. In addition, we demonstrate that this fusion can be rapidly detected by STAT6 immunohistochemistry which shows a consistent nuclear reallocation. This immunohistochemical assay may prove valuable for the differentiation of HPC and SFT from other mesenchymal neoplasms.

Can a community-based intervention improve the home food environment? parental perspectives of the influence of the delicious and nutritious garden.

OBJECTIVE: To examine changes in parental report of the home food environment during the course of a garden-based fruit and vegetable (FV) intervention for grade school children. METHODS: Self-administered pre-post surveys were completed by parents/caregivers (n = 83). Main outcome measures included: child asking behavior, FV availability/accessibility, parental encouragement, and value of FV consumption. RESULTS: Process evaluation results indicate children shared their garden experiences at home, and as a result, the children's home food environment became increasingly supportive of FV consumption. Parents reported an increase (P < .01) in the frequency that their child asked for FVs. Parental value for FV consumption also improved (P < .01), as did home availability of fruit (P < .05), vegetables (P < .001), and parental encouragement of FVs (P = .06). CONCLUSIONS AND IMPLICATIONS: Community-based interventions that provide activities to engage parents may provide added benefit by improving the home food environment.

A garden pilot project enhances fruit and vegetable consumption among children.

Fruit and vegetable intake among children is inadequate. Garden-based nutrition education programs may offer a strategy for increasing fruit and vegetable intake in children. A 12-week pilot intervention was designed to promote fruit and vegetable intake among 4th to 6th grade children (n=93) attending a YMCA summer camp. Children participated in garden-based activities twice per week. Weekly educational activities included fruit and vegetable taste tests, preparation of fruit and vegetable snacks, and family newsletters sent home to parents. The pilot intervention was evaluated using a pre and post survey to determine participant satisfaction and the short-term impacts of the program. The process evaluation focused on program satisfaction, whereas the short-term impact evaluation assessed fruit and vegetable exposure, preference, self-efficacy, asking behavior, and availability of fruits and vegetables in the home. Data from the impact evaluation were compared from baseline to follow-up using McNemar's test (dichotomous variables) and Wilcoxon signed rank test (scales/continuous variables). Children reported high levels of enjoyment in the intervention activities. Most children (97.8%) enjoyed taste-testing fruits and vegetables. Children also liked preparing fruit and vegetable snacks (93.4%), working in their garden (95.6%), and learning about fruits and vegetables (91.3%). Impact data suggest that the intervention led to an increase in the number of fruits and vegetables ever eaten (P<0.001), vegetable preferences (P<0.001), and fruit and vegetable asking behavior at home (P<0.002). Garden-based nutrition education programs can increase fruit and vegetable exposure and improve predictors of fruit and vegetable intake through experiential learning activities. Participation in the "seed to table" experience of eating may help promote healthful eating behaviors among youth. Food and nutrition professionals should consider garden-based nutrition education programs that connect children with healthful foods through fun, hands-on activities.

Impact of garden-based youth nutrition intervention programs: a review.

Garden-based nutrition-education programs for youth are gaining in popularity and are viewed by many as a promising strategy for increasing preferences and improving dietary intake of fruits and vegetables. This review examines the scientific literature on garden-based youth nutrition intervention programs and the impact on nutrition-related outcomes. Studies published between 1990 and 2007 were identified through a library search of databases and an examination of reference lists of relevant publications. Studies were included if they involved children and adolescents in the United States and examined the impact of garden-based nutrition education on fruit and/or vegetable intake, willingness to taste fruits and vegetables, preferences for fruits and vegetables, or other nutrition-related outcomes. Only articles published in peer-reviewed journals in English were included in the review. Eleven studies were reviewed. Five studies took place on school grounds and were integrated into the school curriculum, three studies were conducted as part of an afterschool program, and three studies were conducted within the community. Studies included youth ranging in age from 5 to 15 years. Findings from this review suggest that garden-based nutrition intervention programs may have the potential to promote increased fruit and vegetable intake among youth and increased willingness to taste fruits and vegetables among younger children; however, empirical evidence in this area is relatively scant. Therefore, there is a need for well-designed, evidenced-based, peer-reviewed studies to determine program effectiveness and impact. Suggestions for future research directions, including intervention planning, study design, evaluation, and sustainability are provided.