scholarly journals Correlation of Brain Tumor-related Epilepsy With Clinicopathological Factors in Gliomas

Author(s):  
Bo Li ◽  
Shunli Jiang ◽  
Guangning Zhang ◽  
Junchen Zhang

Abstract Objectives: Glioma patients with brain tumor-related epilepsy (BTRE) have a complex profile due to the simultaneous presence of two pathologies: glioma and epilepsy. However, the underlying pathophysiology of BTRE remains poorly understood. The purpose of this study is to investigate the correlation between molecular neuropathology and glioma with BTRE.Methods: A retrospective cohort study of 186 glioma patients was evaluated at our hospital, with 64 presenting with BTRE. Chi-square test, spearman rank correlation and multivariate logistic analyses were used to identify clinicopathological factors associated with BTRE. Results: Of the 186 patients examined in this study, 64 (34.4 %) had BTRE. By analyzing the characteristics of these patients, the results showed that patient age (over 40 years; p=0.007), low WHO grade (grade I, II; p = 0.001), IDH-1 positive mutation (p=0.027), ATR-X low expression level (OR=0.44; 95% CI: 0.21, 0.92) and low Ki-67 proliferation index (OR=0.25; 95% CI: 0.10, 0.68) were associated with the occurrence of BTRE. BTRE did not differ by sex, tumor location, expression of olig-2 or CD34. The results of the matching study showed that low Ki-67 proliferation index and negative ATR-X expression level were independent factors for a higher incidence of preoperative seizures in glioma patients. Conclusion: The current study updates existing information on genetic markers in gliomas with BTRE and explores the correlation of a wide range of clinicopathological factors and glioma patients with BTRE. Our study suggests that three putative biomarkers for BTRE: positive IDH1 mutation, low Ki-67 proliferation index and negative ATR-X expression. These factors may provide insights for developing a more thorough understanding of the pathogenesis of epilepsy and effective treatment strategies aimed at seizure control.

2017 ◽  
Vol 34 (2) ◽  
pp. 92-99 ◽  
Author(s):  
Lisa A. Mestrinho ◽  
Hugo Pissarra ◽  
Sandra Carvalho ◽  
Maria C. Peleteiro ◽  
Jerzy Gawor ◽  
...  

Grade and labeling indices for immunohistochemical tumor proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA) were evaluated in 36 cases of canine oral squamous cell carcinoma (OSCC) based upon intraoral location. Grade was significantly associated with location ( P = .035). Grade II tumors were most frequently diagnosed. Grade I tumors were identified in the gingiva and the buccal mucosa, and grade III tumors were seen in the gingiva and the tonsillar region. Animals with tumors arising from the tonsils and of the tongue tended to be older ( P = .007), and those in the former group were more likely to have metastatic disease at the time of diagnosis ( P = .001). Mean expression of PCNA and Ki-67 proliferation index (PI) for all tumors were 62.54% and 50.70%, respectively, and there was a statistical significant association between the 2 variables ( R = .70; P < .001). Proliferation index was not associated with any of the intraoral locations evaluated, but higher PCNA PI was significantly associated with grade ( P = .031). Ki-67 PI was significantly associated with lymph node metastasis at the time of diagnosis, especially for OSCC of gingival location ( P = .028). The results obtained in this study are preliminary but clinically relevant, since they provide information that can explain differences in biologic behavior among intraoral locations and contribute to more accurate tumor staging to support the choice for different treatment strategies available for OSCC.


2016 ◽  
pp. 158-164
Author(s):  
A.A. Sukhanova ◽  
◽  
S.V. Nespryadko ◽  
M.M. Melnik ◽  
M.Yu. Yegorov ◽  
...  

The aim was to study the expression features of proliferation marker Ki-67 and estrogen receptor (ER) in cells of benign (BeEOT) and borderline epithelial ovarian tumors (BoEOT) and to determine their value for clinical prognosis and tumor justification tactics for further treatment. Patients and methods. Studies conducted on the material of 60 patients with BeEOT and BoEOT who underwent examination and treatment during 2010-2016. It was studied specific menstrual dysfunction, ultrasound data and colour doppler research, the performance of serum tumor markers, morphological and immunohistochemical studies were conducted to determine the Ki-67 and ER in samples of BeEOT and BoEOT. Results. The results of Ki-67 expression determining indicate the heterogeneity of individual performance fluctuations from 0% to 15%. The average value of the proliferation index (PI) was 5.07±0.47%, the median (ME) was 4%. It is determined that almost all BeEOT (96.7%) was marked by lower PI<10%, while 5 of 10 serous borderline cystadenomas (50%) and 1 of 10 mucinous borderline cystadenomas (10%) were attributed to high proliferation (IPі10%) tumors. It is found that in most cells of BeEOT and BoEOT was available the expression of ER. Individual values of ER expression level ranged from 2.0% to 90,0%. The average value of the IM (index marks) ER was 45.08±3.2%, ME=49.5%. It is found a significant decrease (p<0.05) in the ER expression level in EOT of late reproductive age patients compared with younger ones, as well as in cells of BoEOT compared to BeEOT. Conclusion. Some associative connection between the expression of Ki-67 and ER with EOT malignancy potential demonstrates the need to use them for tumor course prognosis and appointment of adequate individualized treatment strategy of patients. Key words: benign and borderline ovarian tumors, immunohistochemical studies, Ki-67, estrogen receptors.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii372-iii372
Author(s):  
Hiroyuki Uchida ◽  
Nayuta Higa ◽  
Hajime Yonezawa ◽  
Tatsuki Oyoshi ◽  
Koji Yoshimoto

Abstract Gliomas in children are rarer than in adult, then treatment strategies might vary from facility to facility. We report clinical features and outcome of pediatric glioma in our institution. Twenty-nine patients diagnosed with glioma, exclude ependymoma, 14 boys and 15 girls, among 98 pediatric brain tumor patients treated at Kagoshima University Hospital since 2006 were reviewed histopathology, extent of resection, adjuvant therapy and outcome, etc. Mean age at surgery was 10.4 (S.D. 5.6) years. Median follow-up period was 19.1 months. Histopathological diagnosis comprised 8 pilocytic astrocytoma, 3 ganglioglioma, 2 subependymal giant cell astrocytoma, 5 WHO grade Ⅱ astrocytoma, 8 glioblastoma, and desmoplastic infantile astrocytoma, anaplastic astrocytoma and astroblastoma were one case each. Tumor resection was performed in 24 cases, and 5 cases underwent biopsy. Chemotherapy was performed in 15 cases and irradiation was performed in 9 cases. Out of 5 WHO grade Ⅱ astrocytoma cases, 2 cases underwent biopsy following chemotherapy, 1 case underwent biopsy only and other 1 case underwent total resection. The four cases show long survival ranged from 71 to 136 months without irradiation. All of eight glioblastoma cases show poor prognosis ranged from 8.6 to 26.7 months regardless of chemo-radiotherapy. In management for pediatric brain tumor patients, irradiation is often laid over until recurrence. In WHO grade Ⅱ astrocytoma, the treatment strategy might be reasonable using appropriate chemotherapy even though biopsy cases.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
Nozomi Hirai ◽  
Toshiya Ichinose ◽  
Sho Tamai ◽  
Riho Nakajima ◽  
Hemragul Sabit ◽  
...  

Abstract The Eph receptor/ephrin ligand system is the largest family of tyrosine kinase with signaling modality through cell to cell adhesion. Eph/ephrin is involved in malignant phenotype such as cell proliferation, migration, and invasion in cancer cells. Although the functions of the Eph receptors in glioblastoma have been elucidated, little is known on ephrin ligands, especially ephrin-A2. Here, we analyze the expression of ephrin-A2 in gliomas using surgical specimens. The expression level of ephrin-A2 mRNA in 14 normal brains and glioma (WHO grade II 13, III 10, and IV 40) was measured by quantitative real-time PCR. Ephrin-A2 expression level was significantly lower in glioblastoma than in normal brain (p= 0.0127). When we divided the glioblastoma cases into high and low ephrin-A2 expression groups based on the median value, the overall survival (OS) was significantly longer in the high expression group compared with the low expression group (p= 0.034, median 24.0 and 14.0 months, respectively). Furthermore, multivariate analysis of factors related to OS with ephrin-A2 expression level and general prognostic factors (age, sex, preoperative KPS, surgical resection rate, radiochemotherapy, IDH1 mutation, MGMT promotor methylation) was performed. Ephrin-A2 expression level (p= 0.039), MGMT promotor methylation (p= 0.0001), and surgical resection rate (p= 0.017) were identified as independent prognostic factors. Taken together, ephrin-A2 is an independent favorable prognostic factor in glioblastoma.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
David Black ◽  
Sadahiro Kaneko ◽  
Anna Walke ◽  
Simone König ◽  
Walter Stummer ◽  
...  

Abstract5-Aminolevulinic acid (5-ALA)-mediated fluorescence does not effectively depict low grade gliomas (LGG) or the infiltrative tumor portion of high-grade gliomas (HGG). While spectroscopy improves sensitivity and precision, this is currently limited by autofluorescence and a second protoporphyrin IX (PpIX) fluorescence state at 620 nm. We investigated the autofluorescence to better characterize the present spectra and thus increase PpIX quantification precision and sensitivity. This study included 128 patients undergoing surgery for malignant glioma. 5-ALA (Gliolan) was administered before anesthesia, and fluorescence was measured using a hyperspectral device. It was found that all 2692 measured spectra consisted of contributions from 620 to 634 nm PpIX, NADH, lipofuscin, and flavins. The basis spectra were characterized and their use in spectral unmixing led to 82.4% lower fitting error for weakly fluorescing areas (p < 0.001), and 92.3% fewer false positive tumor identifications in control measurements (p = 0.0065) compared to previous works. They also decreased the PpIX620 contribution, thus halving the mean Ratio620/634 (p < 0.001). The ratio was approximately 0 for HGGs and increasing for LGGs, as demonstrated previously. Additionally, the Ratio620/634, the MIB-1/Ki-67 proliferation index, and the PpIX peak blue-shift were found to be significantly related to WHO grade, fluorescence visibility, and PpIX contribution (p < 0.001), and the value of these three as quantitative biomarkers is discussed.


2018 ◽  
Vol 18 (3) ◽  
pp. 52-56
Author(s):  
D P Kovtun ◽  
N M Anichkov ◽  
O G Polushin ◽  
E V Ponomaryeva ◽  
A I Lyubimov ◽  
...  

Aim of the study. To analyze the correlation between proliferative activities determined on the basis of routine histological staining and immunohistochemical reaction to the nuclear antigen Ki-67 in colorectal adenocarcinomas. Methods. Thirty adenocarcinomas of the colon and rectum were retrospectively evaluated. Evaluation of proliferative activity was performed on serial histological preparations stained with hematoxylin and eosin and treated with antibodies to Ki-67. Calculation was carried out in the “hot spots” under four microscope high power fields (≈1 mm2). Results. An estimate of the Kendall rank correlation coefficient demonstrated a high degree of direct relationship between the number of mitoses counted by routine staining and proliferative activity estimated by the immunohistochemical method (τ = 0.708, p < 0.05). All observations on the dispersion diagram could be divided into three “cloud” clusters with similar values for Ki-67 with practically the same number of mitoses. Conclusions. On the basis of routine histological examination, it is possible to separate colorectal carcinomas from tumors with a low (1-2/mm2), moderate (3-5/mm2), and high (≥6/mm2) mitotic activity corresponding to the proliferation index values of Ki-67 <30%, 30%-50%, and >50%, respectively.


Endocrine ◽  
2020 ◽  
Author(s):  
Dimitrios Papantoniou ◽  
Malin Grönberg ◽  
Kalle Landerholm ◽  
Staffan Welin ◽  
Barbara Ziolkowska ◽  
...  

Abstract Purpose Small intestinal neuroendocrine tumours (siNETs) with a Ki-67 proliferation index between 3 and 20% belong to WHO grade 2. Response to treatment may be monitored by blood chromogranin A (CgA) and urine 5-hydroxyindoleacetic acid (5HIAA). The aim of this retrospective study was to investigate the prognostic value of baseline CgA and 5HIAA and of the early biochemical response to treatment, and to compare different cut-off values used in the literature. Methods A retrospective cohort study of 184 patients with siNET Grade 2 treated with somatostatin analogues (SSA), interferon-alpha (IFN) or peptide receptor radionuclide therapy (PRRT). Results Baseline CgA was a statistically significant prognostic marker for both cancer-specific survival (CSS) and progression-free survival (PFS). A cut-off of 5 × ULN (upper limit of normal) was best discriminative in most cases, but 2 × ULN discriminated better for SSA. Baseline 5HIAA was a prognostic marker for CSS in treatment with IFN and PRRT, but not for single SSA. Early changes of CgA and 5HIAA correlated well with CSS (HR 3.18, 95% CI 1.82–5.56 and HR 1.47, 95% CI 1.16–1.86) and PFS (HR 3.08, 95% CI 1.86–5.10 and HR 1.37, 95% CI 1.11–1.68) for SSA, but not for PRRT. Conclusions Baseline CgA and to a lesser extent 5HIAA are associated with CSS irrespective of treatment used, and with PFS after PRRT, and 5 × ULN provides best discrimination in many, but not all, cases. Early reductions of CgA and 5HIAA are prognostic for treatment with SSA, but not PRRT.


Author(s):  
Christian Mirian ◽  
Simon Skyrman ◽  
Jiri Bartek ◽  
Lasse Rehné Jensen ◽  
Lars Kihlström ◽  
...  

Abstract BACKGROUND There are examples of incongruence between the WHO grade and clinical course in meningioma patients. This incongruence between WHO grade and recurrence has led to search for other prognostic histological markers. OBJECTIVE To study the correlation between the Ki-67 proliferative index (PI), risk of recurrence, and recurrence rates in meningioma patients. METHODS We prospectively collected pathological diagnosis of de novo consecutive meningiomas. In total, we followed 159 patients with clinical controls until recurrence, death, or emigration. We estimated the correlation between risk of recurrence and Ki-67 PI when adjusted for age at diagnosis, sex, WHO grade, extent of surgical resection, and tumor location. We estimated the cumulative incidence of recurrence when considering death without recurrence a competing risk. We report recurrence rates per 100 person-years. RESULTS A 1%-point increase of Ki-67 PI yielded a hazard ratio of 1.12 (95% CI: 1.01-1.24) in a multivariate analysis. The cumulative incidence of recurrence was 3% for Ki-67 0% to 4% vs 19% for Ki-67 &gt; 4% meningiomas after 1 yr, but 24% vs 35%, respectively, after 10 yr. There was no significant difference in mean Ki-67 PI between nonrecurrent and recurrent meningioma in a 2-sample t-test (P = .08). The strongest relationship was detected between Ki-67 PI and time to recurrence: Ki-67 &lt; 4% meningiomas recurred after median 4.8 yr, compared to 0.60 to 0.75 yr for patients with higher Ki-67 PI. CONCLUSION Ki-67 PI was a marker for time to recurrence rather than a predictor of recurrence. Ki-67 PI may be utilized for patient tailored follow-up.


Author(s):  
Akihiro Ohmoto ◽  
Hirofumi Rokutan ◽  
Shinichi Yachida

Pancreatic neuroendocrine neoplasms (pNENs) are rare tumors accounting for only 1-2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2 and neuroendocrine carcinoma: NEC) on the basis of Ki-67 proliferation index and mitotic count according to the 2010 WHO classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as MEN1, DAXX and ATRX, whereas NECs have an inactivation of TP53 and RB1, and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic backround together with preclinical studies to develop new agents, including those already under investigation for SCLC, will be needed to improve the prognosis.


2021 ◽  
Vol 10 ◽  
Author(s):  
Shunnan Ge ◽  
Yingwu Shi ◽  
Gang Zhu ◽  
Songlun Li ◽  
Yaning Cai ◽  
...  

PurposeGlioma is one of the most common tumors of the central nervous system, and many patients suffer from recurrence even after standard comprehensive treatment. However, little is known about the molecular markers that predict the recurrence patterns of glioma. This study aimed to demonstrate the correlations between molecular markers and glioma recurrence patterns, which included local/nonlocal recurrence and paraventricular/nonparaventricular recurrence.MethodsImmunohistochemical techniques were used to assess the molecular markers of 88 glioma tissues following surgical resection. The recurrence patterns were divided into local recurrence, marginal recurrence, distant recurrence, multirecurrence, and subarachniod recurrence, with the last four recurrence patterns being collectively called nonlocal recurrence. According to whether the recurrence invaded ventricles, the nonlocal recurrence patterns were divided into paraventricular and nonparaventricular recurrence. Then, we compared the different recurrence patterns and their clinical characteristics, focusing on the expression of molecular markers.ResultsMore patients in the nonlocal recurrence group received combined radiotherapy and chemotherapy than patients in the local recurrence group (p=0.019). Sex, age, extent of surgery, time to recurrence, tumor location, size, and WHO grade were not different in the defined groups (P&gt;0.05). Recurrent tumor volume and WHO grade were significantly different between the paraventricular and nonparaventricular recurrence groups (p=0.046 and 0.033). The expression of Ki-67, P53, and PCNA in the nonlocal recurrence group was significantly higher than that in the local recurrence group (p=0.015, 0.009, and 0.037), while the expression of S-100 in the nonlocal recurrence group was significantly lower than that in the local recurrence group (p=0.015). Cox regression indicated hazard ratio (HR) for high expression level of PCNA associated with non-local recurrence was 3.43 (95% CI, 1.15, 10.24), and HR for high expression level of MGMT associated with paraventricular recurrence was 2.64 (95% CI, 1.15,6.08).ConclusionsKi-67, P53, PCNA, and MGMT might be important clinical markers for nonlocal recurrence and paraventricular recurrence.


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