scholarly journals Clinical and Prognostic Implications of 1p/19q, IDH, BRAF, MGMT Promoter, and TERT Promoter Alterations, and Expression of Ki-67 and p53 in Human Gliomas

2021 ◽  
Vol Volume 13 ◽  
pp. 8755-8765
Author(s):  
Zixi Yang ◽  
Feng Ling ◽  
Sibei Ruan ◽  
Jiajia Hu ◽  
Mingxi Tang ◽  
...  
Keyword(s):  
Human Gliomas ◽  
Ki 67 ◽  
Tert Promoter ◽  
Mgmt Promoter ◽  
Prognostic Implications

Prognostic Implications of p53 Nuclear Overexpression and High Proliferation Index of Ki-67 in Adult Soft-Tissue Sarcomas

1994 ◽  
Vol 86 (7) ◽  
pp. 549-554 ◽  
Author(s):  
Marija Drobnjak ◽  
Esther Latres ◽  
Daphna Pollack ◽  
Martin Karpeh ◽  
Maria Dudas ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Proliferation Index ◽  
Ki 67 ◽  
Prognostic Implications

scholarly journals P14.95 Is the pathological-grade relevant in “IDH-wild type, TERT-mutant” diffuse-gliomas? An analysis in 147 patients

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii90-iii90
Author(s):  
A E Danyeli ◽  
C B Akyerli ◽  
A Dinçer ◽  
E Coşgun ◽  
U Abacıoğlu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Lower Grade ◽  
Wild Type ◽  
Ki 67 ◽  
Who Grade ◽  
Free Survival ◽  
Tert Promoter ◽  
Diffuse Gliomas

Abstract BACKGROUND Although the word “glioblastoma” still denotes a grade-IV pathology, basic molecular studies have clearly indicated that a significant proportion of lower-grade gliomas harbor genetic alterations typical of glioblastomas. Based on these findings cIMPACT-NOW update 3 has defined an entity called the “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. A TERT-promoter mutation is one of these typical molecular markers of glioblastomas. In this study we analyzed IDH-wild type, TERT-mutant diffuse gliomas of different pathological grades to look for differences in demographic, clinical and survival characteristics. MATERIAL AND METHODS 147 adult hemispheric diffuse-gliomas with wild-type IDH1/2 and mutant TERT-promoter (C228T or C250T) were retrospectively analyzed. Primary thalamic, cerebellar brainstem or spinal cases were excluded. 126 (86%), 16(11%) and 5(3%) patients were WHO grade IV, III and II respectively. After surgical treatment or stereotactic biopsy all patients underwent chemoradiation. Median follow-up was 16mo (1–110). Tumors of different grades were compared for age, gender, multifocality, gliomatosis pattern, Ki-67 index, progression-free survival and overall-survival. RESULTS Mean age at presentation for grade II, III and IV were comparable (58.1, 58 and 58.1; ANOVA, p=0.72). There was a slight male predominance in both lower-grades and WHO-grade IV (M:F ratios 1.625 and 1.74). Mean Ki-67 index was significantly higher in higher grades (0.06, 0.14 and 0.25 for grades II, III and IV; ANOVA, p=0.001). Multifocality was comparable (chi-sq, p=1) in lower-grades (3/21; 14.3%) vs. WHO-grade IV (18/126; 14.3%). Gliomatosis pattern was comparable (chi-sq, p=0.095) in lower-grades (2/21; 9.5%) vs. (3/126; 2.3%). Median recurrence free survival (RFS) was 16 months (0–63) in lower-grades and 8months (1–50) in WHO-grade IV. PFS was significantly different between 3 WHO-grades (Log rank, p=0.007) and also between lower-grades and WHO-grade IV (Log rank, p=0.002). Median overall survival was 26 months(2–110) in lower-grades and 15mo(1–91) in WHO-grade IV. OS was significantly different between 3 WHO-grades (Log rank, p=0.014) and also between lower-grades and WHO-grade IV (Log rank, p=0.007). CONCLUSION Increasing pathological grades of hemispheric “IDH-wild type, TERT-mutant diffuse gliomas” have similar demographic and clinical characteristics but incrasing proliferation indices, decrasing progression free survival and shorter overall survival. The findings may be suggesitve of different grades of one common tumor entity.

The clinical significance of telomerase reverse transcriptase (TERT) promoter mutations, telomere length and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status in newly diagnosed and recurrent IDH-wildtype glioblastoma (GBM) patients (PTS): A large mono-institutional study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2053-2053
Author(s):  
Giuseppe Lombardi ◽  
Silvia Giunco ◽  
Francesco Cavallin ◽  
Chiara Angelini ◽  
Mario Caccese ◽  
...  
Keyword(s):  
Telomere Length ◽  
Methylation Status ◽  
Mgmt Promoter Methylation ◽  
Newly Diagnosed ◽  
Mgmt Methylation ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Mgmt Promoter ◽  
Promoter Mutations ◽  
Mgmt Promoter Methylation Status

2053 Background: the clinical significance of TERT promoter mutations, telomere length and their interactions with MGMT promoter methylation status in patients with IDH-wildtype GBM patients remain unclear. We performed a large mono-institutional study to better investigate their impact and their interaction on clinical outcomes Methods: TERT promoter mutations (C228T and C250T), relative telomere length (RTL) and MGMT methylation status were assessed in 278 newly diagnosed and in 65 recurrent IDH-wildtype GBM PTS which were treated at Veneto Institute of Oncology (Padua, Italy) from Dec 2016 to Jan 2020. We have retrospectively explored association between gene characteristics and neuroradiological response (RANO criteria), progression-free survival (PFS), overall survival (OS). Telomere length was measured by monochrome multiplex PCR and RTL values were calculated as a telomere/single-copy gene ratio Results: characteristics of newly diagnosed GBM PTS were: median age 63 ys, ECOG PS 0-1 in 71% of PTS, radical surgery in 38%, 78% received radiation therapy plus TMZ, MGMT was methylated in 53%, TERT promoter was mutated in 80% (75% C228T, 25% C250T), median RTL was 1.57 (range 0.4-11.37). Objective response rate was reported in 15% of PTS, median OS was 15ms (95% CI 13-18ms), median PFS was 8ms (95% CI 7-9ms). At multivariable analysis, TERT promoter mutations and RTL were not associated with clinical outcomes; about OS, TERT promoter mutations and RTL reported a HR of 1.05 (95% CI 0.64-1.64) and 0.99 (95% CI 0.89-1.10), respectively; MGMT methylated tumors showed significant improved PFS and OS with a HR of 0.54 (95% CI 0.40-0.71) and 0.47 (95% CI 0.34-0.64), respectively. All interactions among MGMT status, TERT mutation status and RTL were not statistically significant. Characteristics of recurrent GBM PTS were: median age 55 ys, ECOG PS 0-1 in 60% of PTS, MGMTmet in 37%, TERT promoter mutations in 75% (75% C228T, 25% C250T), RTL was 1.67 (range 0.68-8.87). At multivariable analysis, only MGMT methylated tumors resulted significantly associated to prolonged OS (HR 0.16; 95% CI 0.07-0.40). No gene interaction was significant. Conclusions: for the first time worldwide, we analyzed the impact of TERT promoter mutations, RTL and MGMT methylation status in both newly diagnosed and recurrent IDH-wildtype GBM PTS. TERT promoter status and RTL were not associated with clinical outcomes at both diagnosis and relapse. MGMT promoter methylation status was the only prognostic factor in both cases. No significant interaction was demonstrated between TERT promoter mutations, RTL and MGMT methylation status.

Abstract C118: TERT promoter mutations in human gliomas.

2013 ◽  
Author(s):  
Jorge Lima ◽  
Rui M. Reis ◽  
Telmo Catarino ◽  
Joana Peixoto ◽  
Joao Vinagre ◽  
...  
Keyword(s):  
Human Gliomas ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

scholarly journals P1.02-037 Pulmonary Carcinoid Tumors: A Prognostic Implications of Ki-67 Proliferative Index

2017 ◽  
Vol 12 (11) ◽  
pp. S1938
Author(s):  
R. Langfort ◽  
P. Rudzinski ◽  
E. Szczepulska ◽  
B. Maksymiuk ◽  
T. Orlowski ◽  
...  
Keyword(s):  
Carcinoid Tumors ◽  
Proliferative Index ◽  
Ki 67 ◽  
Pulmonary Carcinoid ◽  
Prognostic Implications
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