scholarly journals Clinicopathological evaluation of immunohistochemical Ki-67 and endothelial nitric oxide synthase expression in intracranial ependymoma

2008 ◽  
Vol 31 (4) ◽  
pp. 206 ◽  
Author(s):  
Xuetao Yan ◽  
Xiaoli Cheng ◽  
Juyin Liu ◽  
Dongqin Luo ◽  
Xianghu He ◽  
...  

Purpose: To analyze the association between Ki-67 and eNOS expression with the pathological grades of patients with intracranial ependymomas, and to determine its value in distinguishing the progression of the disease. Methods: A clinicopathological study was undertaken in 82 patients with intracranial ependymomas. Tissue samples, obtained by tumour resection, were divided into three groups: low-grade, mid-grade and high-grade ependymomas. Tissue samples obtained from 15 patients with brain contusion were used as control. Immuno-histochemical staining was performed to analyze the association between Ki-67 and eNOS expression with various tumour grades. The cell proliferating marker Ki-67 was assessed by positive cell count. The levels of eNOS positive expression were evaluated as slight, moderate and intense. Results: 48 of 82 cases (58.54%) expressed Ki-67 protein. Expression of Ki-67 and eNOS was negative in all control samples. Positive cell rates were 2.65±0.83 % in the low-grade, 9.63±0.08 % in the mid-grade, and 28.41±0.71 % in the high-grade ependymoma groups. In low-grade ependymomas there were 8 and 12 cases that expressed eNOS slightly or moderately. In the mid-grade ependymoma group eNOS was expressed moderately in 10 cases and intensely in 15. In the high-grade group 20 cases showed intense positive expression of eNOS. The Ki-67 positive cell counts for slight, moderate and intense eNOS expression were 2.20, 6.07 and 22.25, respectively. Conclusion: Ki-67 and eNOS expression in intracranial ependymoma tissue was associated with the histopathological grade and malignant degree.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 94-94
Author(s):  
Song Xue ◽  
Man Hu ◽  
Jinming Yu ◽  
Bingjie Fan ◽  
Ji Ma

94 Background: The treatment strategies for glioma, especially glioblastoma multiforme, are not effective. The programmed death ligand 1 (PD-L1) immune escape and increased angiogenesis may be two of the underlying sources of treatment resistance. However, the relationship between these pathways in human glioma is still unknown. Methods: Data for 64 patients with primary glioma recorded from June 2007 to December 2013 in Shan Dong Cancer Hospital were immunohistochemically evaluated for the expressions of PD-L1, VEGF, MMP-9 and KI-67 index. Image ProPlus software was used to quantify the mean optical density (MOD) of the immunohistochemical image. Results: PD-L1 expression was observed in 65.22% of low-grade glioma and 90.24% of high-grade glioma, respectively. The whole expression rate of PD-L1 in glioma was 81.25%. The expression of PD-L1 is significantly related to pathological grade ( p <0.001), VEGF ( p= 0.017) and KI-67 index ( p= 0.009). The mean of PD-L1 MOD in High-grade group was 0.1144±0.02754, higher than that in low-grade group, 0.005129±0.001441 ( p= 0.004). In addition, Expression of VEGF, MMP-9 and KI-67 was significantly different between low-grade and high-grade gliomas ( p= 0.008, 0.04, 0.004 for VEGF, MMP-9 and KI-67, respectively). When analyzed as a continuous variable, the expressions of PD-L1 was positively correlated with VEGF (r = 0.392, p= 0.001) and KI-67 (r = 0.388, p= 0.001). Conclusions: These data suggest, for the first time, that PD-L1 play an important role in glioma angiogenesis and proliferation potential, providing the possibility for considering additional combinations of targeted VEGF therapies and anti-PD-L1 immunotherapy for the treatment of human brain glioma.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Tao Mei ◽  
Zhengjun Wang ◽  
Jianwu Wu ◽  
Xianhua Liu ◽  
Wei Tao ◽  
...  

Aim. To investigate the expression of glucose transporter 3 (GLUT3) and hypoxia-inducible factor-1α protein (HIF-1α) in meningiomas and analyze the correlation between GLUT3 and HIF-1α expression with the pathological grade of peritumoral brain edema (PTBE) of meningiomas. Methods. In this cross-sectional study, we analyzed meningioma specimens from 160 patients collected from January 1, 2014, to December 1, 2017, by dividing them into a low-grade (WHO I) or high-grade (WHO II and WHO III) group. Immunohistochemical analyses were used to detect the expression level of GLUT3 and HIF-1α in the tumor specimens. Results. The proportion of GLUT3-positive staining in tumors sized <4 cm, 4–6 cm, and>6 cm was 35.9% (37/103), 63.6% (28/44), and 53.8% (7/13), respectively (P=0.007). The proportion of HIF-1α-positive staining in tumors sized <4 cm, 4–6 cm, and >6 cm was 41.7% (43/103), 68.2% (30/44), and 38.5% (5/13), respectively (P=0.010). The proportion of GLUT3-positive staining in the high-grade group and low-grade group was 70.8% (34/48) and 33.9% (38/112), respectively (P<0.001). The proportion of HIF-1α-positive staining in the high-grade group and low-grade group was 62.5% (30/48) and 42.9% (48/112), respectively (P=0.023). GLUT3-positive expression in meningioma PTBE grades 0, I, II, and III was 20.3% (13/64), 41.2% (14/34), 63.6% (21/33), and 82.8% (24/29), respectively (Bonferroni-corrected, P<0.001, α/6=0.008). HIF-1α-positive expression in meningioma PTBE grades 0, I, II, and III was 34.4% (22/64), 47.1% (16/34), 54.5% (18/33), and 75.9% (22/29), respectively (Bonferroni-corrected, P=0.003, α/6=0.008). Spearman’s correlation analysis revealed a correlation between the expression of GLUT3 and HIF-1α in meningiomas (r=0.463, P<0.001). Multivariate analysis revealed that GLUT3-positive expression, HIF-1α-positive expression, and high pathological grade were associated with the development of PTBE (P<0.05). Conclusions. GLUT3 and HIF-1α expression in meningiomas was closely related to the tumor size, pathological grade, and PTBE. This study is the first to report a unique map-like multifocal GLUT3 staining pattern in meningiomas.


2008 ◽  
Vol 132 (2) ◽  
pp. 224-231
Author(s):  
Ying-bei Chen ◽  
Jiangling J. Tu ◽  
Jean Kao ◽  
Xi K. Zhou ◽  
Yao-Tseng Chen

Abstract Context.—Distinguishing low-grade and high-grade noninvasive papillary urothelial carcinoma based on morphologic criteria can be challenging and adjunct markers are highly desirable. Survivin, presumably an antiapoptotic protein, was previously proposed as a prognostic marker for urothelial carcinoma. Objective.—To assess interobserver variability by 2004 World Health Organization classification and the value of survivin and Ki-67 as potential markers for grading noninvasive papillary urothelial carcinoma. Design.—Fifty-one bladder biopsies were graded blindly by 5 experienced general surgical pathologists. The protein and messenger RNA expression of survivin and Ki-67 was evaluated by immunohistochemistry and quantitative reverse transcription–polymerase chain reaction using paraffin-embedded tissue. The immunohistochemistry result was quantitatively analyzed using a computer-based color deconvolution module. Results.—The diagnostic agreement among 5 pathologists was fair to poor, with 32% of the cases graded differently by at least 2 raters. All cases were divided into 3 groups: consensus low-grade, consensus high-grade, and indeterminate. The percentage of urothelial cells with positive survivin nuclear staining (survivin score) was significantly higher in the high-grade than in the low-grade group (P &lt; .001). Survivin score outperformed Ki-67 in separating the high-grade group from the low-grade group and showed a significantly higher predictive accuracy for high-grade recurrence than the histologic grade. The disagreement of grading for the indeterminate group could be resolved by their survivin scores in most cases. Survivin messenger RNA level correlated well with survivin score by immunohistochemistry but was not a more discriminating marker. Conclusions—Significant interobserver variability exists in grading low-grade versus high-grade papillary urothelial carcinoma. Survivin immunohistochemical staining can be a useful adjunct tool for the grading of challenging cases.


Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 317
Author(s):  
Ling-Sai Chang ◽  
Ken-Pen Weng ◽  
Jia-Huei Yan ◽  
Wan-Shan Lo ◽  
Mindy Ming-Huey Guo ◽  
...  

(1) Background: Desquamation is a common characteristic of Kawasaki disease (KD). In this study, we analyzed patients’ varying desquamation levels in their hands or feet, in correlation with clinical presentation, to assess the relationship. (2) Methods: We retrospectively reviewed children with KD. We analyzed their age, laboratory data before intravenous immunoglobulin (IVIG) treatment and coronary artery abnormalities (CAA) based on the desquamation level of their hands and feet. We classified the desquamation level from 0 to 3 and defined high-grade desquamation as grade 2 and 3. (3) Results: We enrolled a total 112 patients in the study. We found the hands’ high-grade desquamation was positively associated with age and segmented neutrophil percentage (p = 0.047 and 0.029, respectively) but negatively associated with lymphocyte and monocyte percentage (p = 0.03 and 0.006, respectively). Meanwhile, the feet’s high-grade desquamation was positively associated with total white blood cell counts (p = 0.033). Furthermore, we found that high-grade hand desquamation had less probability of CAA formation compared with that of a low grade (7.1% vs. 40.8%, p = 0.016). (4) Conclusions: This report is the first to demonstrate that the desquamation level of hands or feet in KD is associated with different coronary artery abnormalities and laboratory findings.


Blood ◽  
2000 ◽  
Vol 95 (2) ◽  
pp. 619-626 ◽  
Author(s):  
Roberto Chiarle ◽  
Leo M. Budel ◽  
Jeffrey Skolnik ◽  
Glauco Frizzera ◽  
Marco Chilosi ◽  
...  

Mantle cell lymphoma (MCL) is an aggressive neoplasm characterized by the deregulated expression of cyclin D1 by t(11;14). The molecular mechanisms responsible for MCL's clinical behavior remain unclear. The authors have investigated the expression of p53, E2F-1, and the CDK inhibitors p27 and p21 in 110 MCLs, relating their expression to proliferative activity (Ki-67). For comparison, they have similarly analyzed low-grade (12 MALT, 16 CLL/SLL) and high-grade (19 DLCL) lymphomas. p53 was detected more frequently in large-cell MCL (l-MCL; 5 of 7) than in classical MCL (s-MCL; 13 of 103) and DLCL (8 of 19). In MCL and DLCL, the percentage of E2F-1+ nuclei was high, correlating with high Ki-67 expression. Most MCLs (91 of 112) and DLCLs (12 of 19) showed a loss of p27; MALT and CLL/SLL, however, were p27 positive. Reverse transcription–polymerase chain reaction and in vitro protein degradation assays demonstrated that MCLs have normal p27 mRNA expression but increased p27 protein degradation activity via the proteasome pathway. Correlation of MCL p53 and p27 expression with clinical data showed an association between reduced overall survival rates and the overexpression of p53 (P = .001), the loss of p27 (P = .002), or both. Loss of p27 identified patients with a worse clinical outcome among p53 negative cases (P = .002). These findings demonstrated that MCL has a distinct cell cycle protein expression similar to that of high-grade lymphoma. The loss of p27 and the overexpression of p53 in MCL are prognostic markers that identify patients at high risk. The demonstration that low levels of p27 in MCL result from enhanced proteasome-mediated degradation should encourage additional clinical trials. (Blood. 2000;95:619-626)


2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S121-S121
Author(s):  
Muhammad Masood Hassan ◽  
Tammey Naab ◽  
Ali Afsari

Abstract Objectives Low-grade papillary urothelial carcinoma (LGUC) has overall a preserved orderly appearance, minimal variability in architecture, and lack of significant cytologic atypia and mitotic activity without pleomorphism. A total of 53.8% of LGUC cases recur with 18.3% progression to high-grade UC. Even focal HGUC in LGUC can be a harbinger of progression. Accurate pathological interpretation is paramount in predicting recurrence and determining treatment. Methods A 63-year-old male with a past medical history of coronary artery disease, benign prostate hyperplasia, and obesity was referred to urology with a chief complaint of chronic hematuria. Cystoscopy with transurethral resection of bladder tumor was performed, which revealed mainly LGUC with focal high-grade-appearing UC. Results Histologic sections revealed papillary architecture with fused fronds, low-grade nuclear atypia, and scattered mitoses comprising 95% of the tissue submitted. No muscular wall invasion by carcinoma was seen. However, in one section, collections of large cells with well-defined cytoplasmic borders, multinucleation, and rare nuclear grooves were identified. The morphology raised the suspicion of a focal HGUC. Diffuse expression of CK20 and low Ki-67 proliferation index (1%) favored umbrella cells. Conclusion Our case reinforces the fact that sectioning can reveal foci, suspicious for HGUC, especially in urothelium. However, proper interpretation of morphology combined with the help of immunohistochemistry aids in accurate diagnosis, which is critical in determining proper clinical management of the patient.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3966-3966 ◽  
Author(s):  
Robert A Baiocchi ◽  
Joseph M. Flynn ◽  
Jeffrey A. Jones ◽  
Kristie A. Blum ◽  
Craig C. Hofmeister ◽  
...  

Abstract Abstract 3966 Background: Dinaciclib (SCH 727965) is a potent and selective inhibitor of the cyclin dependent kinases CDKs 1, 2, 5, and 9, with in vitro activity against lymphoma. Methods: A phase 1 trial of dinaciclib administered by 2-hour i.v. infusion on days 1, 8 and 15 of a 28-day cycle was undertaken in solid tumor patients with 12 mg/m2 established as the recommended phase 2 dose (RPTD). The RPTD was explored in expansion cohorts of up to 10 patients each with low grade lymphomas (primarily follicular lymphoma (FL)), and intermediate/high grade lymphomas (diffuse large B-cell lymphoma (DLBCL)). Sixteen patients have been treated with dinaciclib, including 7 with FL, 1 with mantle cell lymphoma (MCL) and 1 with marginal zone lymphoma (MZL) in the low grade group and 7 with DLBCL in the intermediate/high grade group. Patient median age was 66 (range 43–82) and the median number of prior therapies was 2.5 (range 1–8). All patients received prior rituximab and 4 patients had previously received flavopiridol. All patients were treated with dinaciclib at the 12 mg/m2 dose. Dose de-escalation to 10 mg/m2 was required in 2 patients during treatment. The median number of cycles administered was 3 (range 1–9) with 3 patients continuing treatment for 3 cycles, 4 for 6 cycles, and 1 for 9 cycles. Of the 16 lymphoma patients treated, 2 remain on treatment. Response: Responses were assessed using the revised Cheson criteria for lymphoma (J Clin Oncol 25: 579-86, 2007). One partial response in a patient with DLBCL was observed with an 85% decrease in tumor mass. This patient, previously treated with R-CHOP from May-August 2008 and R-ICE from December 2008-March 2009, was able to continue on to autologous stem cell transplantation for potential curative salvage. Activity not meeting criteria for partial response was seen in 2 patients with FL (decreased tumor mass of 27% and 39%, respectively) and one patient with MCL (8% decrease in tumor mass). Toxicity: Treatment-related adverse events occurring in ≥ 25% of pts included anemia, cytokine release syndrome, nausea, vomiting, diarrhea, fatigue, leucopenia, lymphopenia, neutropenia, and thrombocytopenia. The most common CTCAE v3.0 treatment-related grade 3 and 4 toxicities, occurring in 3 or more patients, were leukopenia, lymphopenia, and neutropenia. Cytokine release syndrome was observed in 4 patients, was manageable with dexamethasone and did not prevent continued treatment on protocol. Conclusion: Dinaciclib demonstrates clinical responses in heavily pre-treated lymphoma patients supporting further study in lymphoma and other hematologic malignancies. Updated information with longer follow-up will be presented. Disclosures: Off Label Use: SCH 727965 is an investigational drug. Small:Merck & Co.: Employment, Equity Ownership. Statkevich:Merck & Co.: Employment, Equity Ownership. Bannerji:Merck & Co: Employment, Equity Ownership.


2011 ◽  
Vol 59 (11) ◽  
pp. 1022-1030 ◽  
Author(s):  
Péter Törzsök ◽  
Péter Riesz ◽  
István Kenessey ◽  
Eszter Székely ◽  
Áron Somorácz ◽  
...  

Updated classification of urothelial cell cancer differentiates low-grade and high-grade cancers, which determines potential clinical outcome. Substantial interobserver variability necessitates new biomarkers to ensure classification. Claudins’ specific expression pattern characterizes normal tissues, different tumor types, and defined grades of tumor differentiation. The aim of this study was to examine the expression pattern of claudins and proliferation marker Ki-67 in low-grade and high-grade urothelial cell cancers compared with independent control samples of non-tumorous urothelium, as well as to reveal the predictive usefulness of claudins. The expression of claudins-1, -2, -3, -4, -5, -7, and -10 and Ki-67 was studied with quantitative immunohistochemistry and real-time RT-PCR with relative quantification in 103 samples: 86 urothelial cell cancers (27 low grade, 59 high grade) and 17 non-tumorous urothelia. Results were analyzed regarding overall survival and recurrence-free period as well. High-grade tumors overall showed significantly higher claudin-4 and Ki-67 and significantly lower claudin-7 expression when compared with low-grade ones. High-grade tumors revealed significantly shorter overall survival in Kaplan-Meier analysis. Claudin-4, claudin-7, and Ki-67 might be used as potential markers to differentiate low-grade and high-grade urothelial cell cancers, thereby possibly enhancing accuracy of pathological diagnosis and adding further information to clinical outcome.


2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Li-qiang Liu ◽  
Li-fei Feng ◽  
Cheng-rui Nan ◽  
Zong-mao Zhao

The present study was conducted to investigate the clinical significance of cAMP responsive element binding protein 3 like 1 (CREB3L1) and pleiotrophin (PTN) expression in prognosis of patients with brain gliomas. Human brain tissue samples were collected from normal glial tissues (control), low- and high-grade glioma tissues. CREB3L1 and PTN expression levels in cells were assessed by immunohistochemistry (IHC), and population distribution of the CREB3L1- and PTN-presenting patients was examined. The CREB3L1 and PTN mRNA expression levels in three types of the brain cells was determined by RT-PCR. Survival rates for population of the CREB3L1- and PTN-presenting patients were examined. CREB3L1+ cell counts were decreased with increased PTN+ cells in the low-grade and high-grade glioma tissues as compared with the control. Population proportion of the CREB3L1+-presenting patients decreased from the control to the high-grade glioma and the population of the PTN+-presenting patients increased in low- and high-grade gliomas as compared with the control (both P<0.05). The decrease in the CREB3L1 mRNA expression was associated with the increase in the PTN mRNA expression in the low- and high-grade gliomas (P<0.05). Survival time for patients with CREB3L1− and PTN+ gliomas was shorter than patients with CREB3L1+ and PTN− gliomas in the investigated cohorts (both P<0.05). There was a relationship between the expression levels of both proteins and survival time. CREB3L1 and PTN expression levels serve as biomarkers with utility in grading gliomas. Absence of CREB3L1 and presence of PTN in brain glioma cells correlate with survival time of the glioma patients.


2001 ◽  
Vol 119 (3) ◽  
pp. 119-121 ◽  
Author(s):  
Edenilson Eduardo Calore ◽  
Carmen Ruth Manzione ◽  
Sidney Roberto Nadal ◽  
Maria José Cavalieri ◽  
Nilda Maria Perez Calore ◽  
...  

CONTEXT: AIDS is one of the most important risk factors for progression and recurrence of anogenital condyloma. In a previous work, we observed that patients with warts and high-grade AIN (HAIN) had recurrences more frequently than did patients with warts without AIN. The mechanisms of this increased incidence of high-grade lesions in AIDS are not known. OBJECTIVE: We studied the expression of the proliferative marker Ki-67 by immunohistochemical methods, in specimens of anal condyloma from HIV+ patients to clarify whether its expression can be associated to the grade of AIN. DESIGN: A retrospective study of hiltological specimens. SETTING: University referral unit. SAMPLE: 34 patients were divided into two groups: (1) condylomas with low grade AIN (LAIN), with 25 patients; and (2) condylomas with HAIN, with 9 patients. In this latter group we examined two areas: 2A (HAIN area) and 2B (LAIN area). MAIN MEASUREMENTS: The immunohistochemical reaction for Ki-67 was done on histological sections. Slices were lightly stained with hematoxylin, to help us in Ki-67 positive cell counting. The percentage of Ki-67 marked nuclei was calculated. We applied one-way variance analysis for statistics. RESULTS: The mean number of Ki-67 positive cells in group 1 was 19.68 ± 10.99; in group 2 (area A) it was 46.73 ± 10.409; and in area B it was 36.43 ± 14.731. There were statistical differences between groups 1 and 2A and between groups 1 and 2B. Ki-67 positive cells predominated in the lower layer in LAIN. Positive Ki-67 cells were found in all layers in group 2A, and in group 2B they predominated in the two lower or in all layers of the epithelium. CONCLUSIONS: Our results suggest that LAIN areas (using routine staining techniques) in HAIN can have a biological behavior more similar to HAIN.


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