Temporal and spatial stability of the EM/PM molecular subtypes in adult diffuse glioma / 医学前沿

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.

Application of integrated theory of health behavior change in pelvic floor muscle exercise of patients with pelvic floor dysfunction after early cervical cancer surgery / 中国实用护理杂志

Objective:To explore the effect of nursing intervention based on the integration theory of health behavior change in pelvic floor muscle exercise of patients with pelvic floor dysfunction (PFD) after early cervical cancer surgery.Methods:A total of 134 patients with pelvic floor dysfunction after early cervical cancer surgery were selected and divided into test group ( n=67) and control group ( n=67) by random digits table method. The test group received three months of pelvic floor muscle exercise based on the theory of healthy behavior change. The control group received conventional pelvic floor rehabilitation care. The Pelvic Floor Distress Inventory-Short Form 20(PFDI-20), Pelvic Floor Impact Questionnaire-7(PFIQ-7), General Self-Efficacy Scale (GSES) and Social Support Rating Scale (SSRS) were evaluated before the intervention (T0), After one month of intervention (T1) and at the end of the intervention (T2). Results:The results of repeated measurement analysis of variance showed significant group/time interaction between PFDI-20 and PFIQ-7 scores ( Finteraction=29.196,13.213, both P<0.05); significant group/time interaction between GSES and SSRS scores ( Finteraction value was 25.664,70.240, both P<0.05). At the end of the intervention, the scores of PFDI-20 and PFIQ-7 in the test group were 66.54±14.04 and 73.20±7.41, which were lower than 77.47±15.91 and 78.39±8.51 in the control group over the same period. The difference was statistically significant ( t value was -4.216, -3.765, both P<0.01); the GSES and SSRS scores of the test group were 2.86±0.30 and 50.37±2.45, which were higher than the control group (2.51±0.34 and 46.42±2.82), the differences between the groups were statistically significant ( t value was 6.447, 8.662, both P<0.01). Conclusion:The nursing intervention plan based on the integration theory of health behavior change can significantly improve the self-efficacy, social support level and quality of life of patients with PFD after early cervical cancer surgery, and enhance the short-term and long-term pelvic floor rehabilitation effect of patients.

Rare primary proximal epithelioid sarcoma in skull base: clinical analysis of four cases / 中华耳鼻咽喉头颈外科杂志

Objective@#To report the clinical and pathological features of primary proximal epithelioid sarcoma (PES) in skull base.@*Methods@#The clinical and pathological features of four cases of PES in skull base from Sanbo Brain Institute of Capital Medical University and Kunming Sanbo Brain Institute were analysed retrospectively.@*Results@#Three cases was female, and one male, the age ranged from 46 to 52 years.All cases occurred in skull base, and sellar region was the main site of involvement.Under the microscope, the tumor cells characterized by epithelioid cell changes, with or without rhabdoid tumor cells.Mitotic figure was active.Immunohistochemical staining showed that AE1/AE3, EMA and CD34 were variously expression in tumor cells.INI-1 protein was lost in all cases.Three cases were detected by FISH, and INI1 (22q11.2) gene locus was absent in them.Three patients died less than 3 months after surgery, and case 4 was under treatment after five months of surgery.@*Conclusions@#Primary PES in skull base mostly occurs in sellar region and its clinical prognosis is poor.It features with epithelioid/rhabdoid tumor cells with lack granuloma structure as distal ES.It has epithelial and mesenchymal differentiation characteristics.CD34 is always positive.INI1 gene deletion and protein loss expression are characteristic molecular alteration of PES.

BRAF V600E mutation and clinicopathologic characteristics in 250 cases of brain tumors associated with epilepsy / 中华病理学杂志

Objective@#To investigate the clinicopathologic characteristics and BRAF V600E mutation of brain tumors associated with epilepsy.@*Methods@#Totally 250 patients with brain tumors associated with epilepsy were included from March 2008 to August 2017 retrospectively at Sanbo Brain Hospital, Capital Medical University.The clinical manifestations, histological features and BRAF V600E mutation results were collected and analyzed.@*Results@#There were 132 males and 118 females, and the male to female ratio was 1.1∶1.0. The age of patients ranged from 2 to 67 years(mean 22 years). The tumors had obvious local space occupying effect on MRI. The temporal lobe was the most common site (44.4%, 111/250). There were 58.4% (146/250) of ganglioglioma (GG), 24.0% (60/250) of dysembryoplastic neuroepithelial tumor (DNT), 12.8% (32/250) of pleomorphic xanthoastrocytoma(PXA), 4.0% (10/250) of angiocentric glioma (AG) and 0.8% (2/250) of papillary glioneuronal tumor (PGNT). Mixed GG, PXA and DNT morphological structures were found in 9 of patients. Among 250 cases, 35 cases were accompanied by focal cortical dysplasia(FCD). BRAF V600E was seen in 43 of 74 (58.1%) GG and 13 of 28 (46.4%) PXA. The most common pathologic grade of GG, DNT, AG and PGNT was WHO I. Some of the tumor cells from GG (34 cases) showed higher proliferative activity (WHO Ⅱ/Ⅲ). Most cases of PXA were WHOⅡand high proliferative activity was seen in nine cases.@*Conclusions@#The association of low-grade glioneuronal tumors with intractable epilepsy was well-recognized. The most common low-grade glioneuronal tumors were GG.GG may occur in any part of the central nervous system, with a predilection for temporal lobe. Each type of low-grade glioneuronal tumors has its own unique histological morphology, but some may show complex features with 2 or 3 mixed components. The occurrence of BRAF V600E mutations in GG is common, and their detection may be valuable for the diagnosis and treatment in GG.

Neuropathologic findings in intractable epilepsy: a clinicopathologic analysis of 822 cases / 中华病理学杂志

Objective@#To investigate the clinicopathologic characteristics of intractable epilepsy.@*Methods@#Based on the classification criteria proposed by the International League Against Epilepsy (ILAE), a retrospective analysis of the pathological characteristics was done in 822 patients who underwent epilepsy surgery in Sanbo Brain Hospital, Capital Medical University, from June 2008 to December 2012.@*Results@#The mean age of epilepsy onset was 9.9 years, mean duration of epilepsy was 11.9 years. Complex partial seizures were the main presenting features. Histopathological study showed 33 cases (4.01%) with mild forms of cortical malformations, 690 cases (83.94%) with focal cortical dysplasia (FCD) and 99 cases with others (including 39 pure hippocampal sclerosis, 20 cystosclerosis, 19 Sturge-Weber syndrome, 8 tuberous sclerosis complex, 6 without significant pathological changes, 5 gyral malformations and 2 hamartoma). Among the 690 FCD cases, 106 were FCD typeⅠ, 91 were FCD typeⅡ and 493 were FCDⅢ(Ⅲa: 160, Ⅲb: 106, Ⅲc: 26 and Ⅲd: 201).@*Conclusions@#FCDⅢd is the most common histopathological subtype causing intractable epilepsy, mainly due to focal hypoxia/ischemia in the perinatal period, which results in scarring of local brain tissue; this is followed by other isolated forms of FCD (FCDⅠand FCDⅡ), and then FCD Ⅲa and FCD Ⅲb. The reason to distinguish isolated forms of FCD (types Ⅰ and Ⅱ) from FCD Ⅲ and to subclassify FCD Ⅲ is to allow better definition of cortical dyslamination. Therefore, the pathogenic factors of intractable epilepsy can be grouped in greater details, and facilitate the diagnosis and potential curative treatment of intractable epilepsy.

Changes of folate receptor -α protein expression in human gliomas and its clinical relevance / 中华外科杂志

<p><b>OBJECTIVE</b>To study the expression level of folate receptor α (FR-α) in glioma tissue and its clinical significance.</p><p><b>METHODS</b>Forty-eight human glioma specimens were collected from patients who underwent surgery from March 2012 to March 2013. These specimens were as follows:12 cases of glioblastoma (WHO IV), 6 cases of astrocytoma of each malignancy grade(WHO II, III), 6 cases of oligodendroastrocytoma of each malignancy grade (WHO II, III), 6 cases of oligodendroglioma of each malignancy grade (WHO II, III ). In addition, 6 cases of normal brain tissue resected from brain traumatic patients were taken as negative control, and one case of placental tissue (had got the consent of the parents and their families) was taken as positive control. The expression level of FR-α in tumor tissues was evaluated by Western blot analysis. The results of Western blot analysis were analyzed by t-test. The expression level of FR-α and Ki-67 in tumor tissues was evaluated immunohistochemistry, the results were analyzed by Kruskal-Wallis test and Nemenyi test. The correlation between the expression level of FR-α and cell proliferation index Ki-67 was analyzed by Pearson correlation analysis.</p><p><b>RESULTS</b>Western blot analysis showed that the FR-α was not expressed in normal brain tissue and oligodendroglioma tissue, but highly expressed in astrocytoma, oligodendroastrocytoma and gliomablastoma. The expression level in WHO III astrocytoma was significantly higher than in WHO II (t = 4.497, P < 0.05). FR-α was also highly expressed in oligodendroastrocytoma and its expression level in WHO III was also significantly higher than in the WHO II (t = 2.876, P < 0.05). Foremore, immunohistochemistry analysis also showed that FR-α was not expressed in oligodendroglioma, but expressed in astrocytoma, oligodendroastrocytoma and gliomablastoma. The positive rate of FR-α of WHO III was significantly higher than the WHO II astrocytoma(57.8% ± 2.2% vs. 45.7% ± 2.3%,χ(2) = 3.871, P = 0.034). In oligodendroastrocytoma, the positive rate of FR-α of WHO III was significantly higher than the WHO II(56.5% ± 5.4% vs. 37.1% ± 5.2%,χ(2) = 4.454, P = 0.021). Moreover, the expression level of FR-α in gliomablastoma was highest in all histological types of gliomas, the positive rate of FR-α was up to 65.0% ± 4.5%. Pearson correlation analysis showed that the positive rate of FR-α was positively correlated with Ki-67 index (r = 0.903, P < 0.05).</p><p><b>CONCLUSIONS</b>FR-α is expressed in astrocytoma, oligodendroastrocytoma and glioblastoma, and the expression level of FR-α is positively correlated with malignancy grade and Ki-67 index. Therefore, FR-α may be applied as a special target for diagnosis and treatment of glioma.</p>

Correlation of chromosome 1p and 19q status and expression of R132H mutant IDH1 protein in oligodendroglial tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>To correlate the presence of chromosome 1p/19q deletion with the expression of R132H mutant IDH1 status in oligodendroglial tumors, and to explore molecular markers for predicting chemosensitivity of oligodendroglial tumors.</p><p><b>METHODS</b>The study included 75 oligodendroglial tumors (38 oligodendrogliomas and 37 oligoastrocytomas). Immunohistochemistry was used to detect the expression of R132H mutant IDH1 protein, and fluorescence in situ hybridization (FISH) was employed to detect 1p/19q deletion.</p><p><b>RESULTS</b>Deletion of chromosome 1p and/or 19q was detected in 37 cases (37/75, 49.3%), among which co-deletion of 1p and 19q was seen in 34 cases (closely correlated, P < 0.01). Oligodendrogliomas WHOIIhad a slightly higher deletion rate than oligodendrogliomas WHO III, although without statistical significance. Oligodendrogliomas WHO IIand WHO III had a significantly higher deletion rate of chromosome 1p/19q than oligoastrocytomas WHO II and WHO III (P < 0.05). While combined loss of 1p/19q was always detected in oligodendrogliomas when FISH was positive, isolated 1p or 19q deletion was only found in oligoastrocytomas. The expression of R132H mutant IDH1 was detected in 51 of 75 cases (68.0%), in which oligodendrogliomas had a higher positive rate than oligoastrocytomas. Statistical analysis demonstrated a significant correlation between the expression of R132H mutant IDH1 protein and the presence of combined 1p/19q deletion in oligodendrogliomas (P < 0.05).</p><p><b>CONCLUSIONS</b>A significant correlation was observed between the expression of R132H mutant protein and 1p/19q LOH.Expression of 132H mutant IDH1 protein is the potential biomarker for predicating the presence of 1p/19q deletion in oligodendrogliomas.</p>

MRI features and pathologic types of benign meningiomas and their correlation with tumor recurrence / 中华放射学杂志

Objective To determine MR manifestations and pathologic types of benign meningiomas and their relationship with tumor recurrence.Methods There were 218 patients (160 females,58 males; age range 4-79 years) with benign meningiomas in the study,including 31 recurrent meningiomas (recurrence group)and 187 primary meningiomas (primary group).All patients were proved by postoperative pathology.Differences of pathological types and MRI manifestations between the recurrence group and the primary group were evaluated by using x2 test and rank sum test.Logistic regression analysis was performed by taking tumor recurrence as the dependent variable,and age,gender,vital structures involvement and pathologic types as independent variables.The recurrent time intervals were compared by rank sum test.Results There were 30 patients with intracranial vital structures involvement or extreintracranial communication tumors in the recurrent group,which was obviously higher than that of the primary group (61 patients).The difference was statistically significant (x2 =57.672,P =0.001).The tumors located in the skull-base and juxtasinus in the recurrent group were obviously more than those in the primary group,and difference was statistically significant (x2 =10.990,P =0.001).Multi-logistic regression analysis showed that the recurrent risk of benign meningiomas was elevated significantly only with vital structure involvement or extre-intracranial communication tumors (wald x2 =31.863,OR =3.820,P =0.001).The recurrent risk of dural sinus involvement was 3.820 times of cerebral artery trunk and cranial nerves involvement,and the risk of the latter was 3.820 times of the non-involved.There was no statistical difference between the two groups in pathology type,location,peritumoral edema,tumor morphology and tumor size.The relapse time of dural sinus involvement and cerebral artery trunk involvement in the recurrent group was 24(13 to 180) and 126(12 to 187) months,respectively.There was significant difference (Z =2.197,P =0.028).Conclusions It is more common that the recurrent benign meningiomas located in the skull base and juxtasinus.The recurrent risk significantly increases when benign meningiomas with vital intracranial structure involved or with extra-intracranial communication tumor.The relapse time of dural sinus involvement is possibly shorter than that of cerebral artery trunk involvement.MRI plays an important role in predicting tumor recurrence and prognosis of benign meningiomas.