scholarly journals Molecular subtyping of ependymoma and prognostic impact of Ki-67

2021 ◽  
Author(s):  
Ka Young Lim ◽  
Kwanghoon Lee ◽  
Yumi Shim ◽  
Jin Woo Park ◽  
Hyunhee Kim ◽  
...  
Keyword(s):  
Cost Effective ◽  
Driver Gene ◽  
Anatomical Location ◽  
Prognostic Impact ◽  
Ki 67 ◽  
Chromosome 1Q ◽  
High Concordance ◽  
Poor Outcomes ◽  
Multiple Recurrences ◽  
Next Generation Sequencing Ngs

AbstractAlthough ependymomas (EPNs) have similar histopathology, they are heterogeneous tumors with diverse immunophenotypes, genetics, epigenetics, and different clinical behavior according to anatomical locations. We reclassified 141 primary EPNs from a single institute with immunohistochemistry (IHC) and next-generation sequencing (NGS). Supratentorial (ST), posterior fossa (PF), and spinal (SP) EPNs comprised 12%, 41%, and 47% of our cohort, respectively. Fusion genes were found only in ST-EPNs except for one SP-EPN with ZFTA-YAP1 fusion, NF2 gene alterations were found in SP-EPNs, but no driver gene was present in PF-EPNs. Surrogate IHC markers revealed high concordance rates between L1CAM and ZFTA-fusion and H3K27me3 loss or EZHIP overexpression was used for PFA-EPNs. The 7% cut-off of Ki-67 was sufficient to classify EPNs into two-tiered grades at all anatomical locations. Multivariate analysis also delineated that a Ki-67 index was the only independent prognostic factor in both overall and progression-free survivals. The gain of chromosome 1q and CDKN2A/2B deletion were associated with poor outcomes, such as multiple recurrences or extracranial metastases. In this study, we propose a cost-effective schematic diagnostic flow of EPNs by the anatomical location, three biomarkers (L1CAM, H3K27me3, and EZHIP), and a cut-off of a 7% Ki-67 labeling index.

scholarly journals Prognostic Significance of Preoperative Neutrophil-to-Lymphocyte Ratio in Patients With Meningiomas

2020 ◽  
Vol 10 ◽  
Author(s):  
Yuki Kuranari ◽  
Ryota Tamura ◽  
Noboru Tsuda ◽  
Kenzo Kosugi ◽  
Yukina Morimoto ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Laboratory Data ◽  
Progression Free Survival ◽  
Cost Effective ◽  
Tumor Location ◽  
Neutrophil To Lymphocyte Ratio ◽  
Ki 67 ◽  
Who Grade ◽  
Lymphocyte Ratio ◽  
Subtotal Removal

BackgroundMeningiomas are the most common benign intracranial tumors. However, even WHO grade I meningiomas occasionally show local tumor recurrence. Prognostic factors for meningiomas have not been fully established. Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic factor for several solid tumors. The prognostic value of NLR in meningiomas has been analyzed in few studies.Materials and MethodsThis retrospective study included 160 patients who underwent surgery for meningiomas between October 2010 and September 2017. We analyzed the associations between patients’ clinical data (sex, age, primary/recurrent, WHO grade, extent of removal, tumor location, peritumoral brain edema, and preoperative laboratory data) and clinical outcomes, including recurrence and progression-free survival (PFS).ResultsForty-four meningiomas recurred within the follow-up period of 3.8 years. WHO grade II, III, subtotal removal, history of recurrence, Ki-67 labeling index ≥3.0, and preoperative NLR value ≥2.6 were significantly associated with shorter PFS (P < 0.001, < 0.001, 0.002, < 0.001, and 0.015, respectively). Furthermore, NLR ≥ 2.6 was also significantly associated with shorter PFS in a subgroup analysis of WHO grade I meningiomas (P = 0.003). In univariate and multivariate analyses, NLR ≥2.6 remained as a significant predictive factor for shorter PFS in patients with meningioma (P = 0.014).ConclusionsNLR may be a cost-effective and novel preoperatively usable biomarker in patients with meningiomas.

scholarly journals Punção Aspirativa de Nódulos da Tiroide: Vale a Pena Repetir?

2017 ◽  
Vol 30 (6) ◽  
pp. 472
Author(s):  
Vera Fernandes ◽  
Tânia Pereira ◽  
Catarina Eloy
Keyword(s):  
Fine Needle Aspiration ◽  
Thyroid Nodules ◽  
Significant Proportion ◽  
Cost Effective ◽  
Needle Aspiration ◽  
Fine Needle ◽  
High Concordance ◽  
Benign Nodules ◽  
Cytology Result ◽  
Undetermined Significance

Introduction: The fine-needle aspiration has a significant role in assessing the malignancy risk of thyroid nodules. There is uncertainty regarding the value of repeat fine-needle aspiration in benign nodules. This study aims to evaluate the concordance of results in consecutive fine-needle aspiration and to study the relevance of repetition in benign results.Material and Methods: Retrospective study of the 4800 thyroid nodules fine-needle aspiration held in Instituto de Patologia e Imunologia Molecular da Universidade do Porto between January 1, 2014 and May 2, 2016. Of the initial sample, we selected the repeated fine-needle aspiration on the same nodule.Results: The first fine-needle aspiration result of the 309 nodules underwent revaluation was non-diagnostic in 103 (33.3%), benign in 120 (38.8%) and atypia/follicular lesion of undetermined significance in 86 (27.8%). The agreement between the first and second fine-needle aspiration was significantly higher in cases with an initial benign result (benign: 85.8%, non-diagnostic: 27.2% and atypia/ follicular lesion of undetermined significance: 17.4%, p < 0.005). The fine-needle aspiration repeating motifs in initially benign nodules (n = 78) were repetition suggestion in 58, nodule growth in 17 and suspicious ultrasonographic features in 3.Discussion: The fine-needle aspiration repetition in nodules with initial non-diagnostic and atypia/follicular lesion of undetermined significance result changed the initial diagnosis in a significant proportion of patients, modifying their therapeutic approach. The high concordance of results in initially benign nodules makes fine-needle aspiration repetition not cost-effective in most cases.Conclusion: The fine-needle aspiration should be repeated when the initial cytology result is non-diagnostic or atypia/follicular lesion of undetermined significance.

scholarly journals Coupling multiplex pre-amplification and droplet digital PCR for longitudinal monitoring ofESR1andPIK3CAmutations from plasma cell-free DNA

2019 ◽  
Author(s):  
Huilan Yao ◽  
Grant Wu ◽  
Subhasree Das ◽  
Crystal MacKenzie ◽  
Hua Gao ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
Hot Spot ◽  
Metastatic Breast ◽  
High Sensitivity ◽  
Cost Effective ◽  
Digital Pcr ◽  
Cost Effective Method ◽  
High Prevalence ◽  
High Concordance ◽  
Hotspot Mutations

AbstractHere we report on the development of a sensitive and cost-effective method to longitudinally trackESR1andPIK3CAmutations from cfDNA in patients with metastatic breast cancer (MBC) using a streamlined and de-centralized workflow. Hotspot mutations inESR1have been shown to cause resistance to aromatase inhibitor–based and anti-estrogenic therapies, whilePIK3CAmutations have high prevalence in MBC. As a result, their utility as circulating biomarkers to predict or monitor response in the clinical development of investigational compounds has been the focus of many studies. Six regions inESR1andPIK3CAgenes containing 20 hotspot mutations were pre-amplified, followed by optimized singleplex ddPCR assays to detect allele frequencies of individual mutations. Without pre-amplification, the limit of detection (LOD) and limit of linearity (LOL) of individual ddPCR assays were at 0.05-0.1% and 0.25% level, respectively. With pre-amplification, the LOD and LOL were slightly elevated at 0.1-0.25% and 0.25-0.5% levels, respectively. High concordance was achieved to the BEAMing assay (Sysmex Inostics) for mutation positive assays (r=0.98, P<0.0001). In conclusion, coupling pre-amplification and ddPCR assays allowed us for the detection of up to 20 hot spot mutations inESR1andPIK3CAwith high sensitivity and reproducibility.

Prognostic impact of recurrence score, endocrine response and clinical-pathological factors in high-risk luminal breast cancer: Results from the WSG-ADAPT HR+/HER2- chemotherapy trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 504-504
Author(s):  
Oleg Gluz ◽  
Ulrike Nitz ◽  
Matthias Christgen ◽  
Michael Braun ◽  
Kerstin Luedtke-Heckenkamp ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
High Risk ◽  
Recurrence Score ◽  
Phase Iii ◽  
Luminal Breast Cancer ◽  
Prognostic Impact ◽  
Treatment Intensification ◽  
Ki 67 ◽  
Prospective Phase ◽  
High Risk Cohort

504 Background: In HR+/HER2- N0-1 early BC, postmenopausal patients (pts) with RS™ > 25 and a substantial proportion of premenopausal pts seem to benefit from addition of adjuvant chemotherapy (CT) to endocrine therapy (ET). However, the magnitude of absolute benefit from this treatment intensification seems to depend on clinical-pathological and biological prognostic factors. For the first time, we present outcome from the CT part of the prospective phase III WSG-ADAPT HR+/HER- trial combining both static (RS in baseline core biopsy (CB) and dynamic (Ki67 response) biomarkers to optimize adjuvant therapy in luminal EBC. Methods: Pts with clinically high-risk HR+/HER2- EBC (cT2-4 OR clinically N+ OR G3 OR Ki67>15%) were initially treated by 3 (+/-1) weeks of standard ET (postmenopausal: mostly AI; premenopausal: TAM) before surgery or sequential CB. Pts with cN2-3 or G3/Ki67>40% were randomized directly to the CT trial. pN0-1 pts with RS0-11 OR RS12-25/ET-response (central Ki67postendocrine<10%) received ET alone; the remaining high-risk cohort was randomized to the CT trial: (neo)adjuvant dose-dense CT (4xPaclitaxelà4xEC q2w vs. 8xNab-Paclitaxel q1wà4xEC q2w) followed by ET. Primary endpoint is efficacy comparison of CT schedules for survival; secondary endpoints reported here involve impacts of key prognostic factors on survival. Kaplan-Meier and Cox proportional hazard models were used to estimate survival curves and hazard ratios. For this analysis, subgroups free of selection bias by RS/ET-response were defined. Results: 5625 pts were screened and 4621 (ITT) entered the trial. After 4.9y median follow-up, higher baseline and post-endocrine Ki-67 levels were associated with poorer iDFS (both p < 0.001). In the CT cohort (n = 2331), higher RS, nodal status, and tumor size were generally associated with poorer iDFS. However, iDFS differed between N1 and N0 status only among younger pts (<50 years). In pts with >4 positive LN (n = 390), lower RS was associated with improved iDFS (RS0-11 vs RS > 25: plog-rank= 0.016, 5y-iDFS 90% vs. 64%). In pts with RS > 25 (n = 965), low Ki67postendocrine, N0 status, and c/pT1 status were associated with improved iDFS. In particular, ET-responders had higher 5y-iDFS (84%) than ET-non-responders (77%; plog-rank= 0.040). Younger patients (<50 years old) with N0-1 RS 12-25/ ET-non-responders treated by CT had non-significantly poorer 5-year iDFS (89%) compared to those with ET-response treated by ET only (92%) (plog-rank= 0.249). Conclusion: First results from the prospective high risk cohort from a large prospective phase III ADAPT trial provide evidence for good prognosis in some pts with >4 positive LN and e.g. low RS. Moreover combination of lower post-endocrine Ki-67 and limited tumor burden may be a promising criterion for CT de-escalation strategies even in patients with high RS. Clinical trial information: NCT01779206.

Machine Learning Perspective in Cancer Research

2021 ◽  
pp. 142-163
Author(s):  
Aman Sharma ◽  
Rinkle Rani
Keyword(s):  
Machine Learning ◽  
Cancer Research ◽  
Expression Profiles ◽  
Genetic Diseases ◽  
Cost Effective ◽  
Healthcare Sector ◽  
Diagnosis And Prognosis ◽  
Cost Effective Approach ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Advancement in genome sequencing technology has empowered researchers to think beyond their imagination. Researchers are trying their hard to fight against various genetic diseases like cancer. Artificial intelligence has empowered research in the healthcare sector. Moreover, the availability of opensource healthcare datasets has motivated the researchers to develop applications which can help in early diagnosis and prognosis of diseases. Further, next-generation sequencing (NGS) has helped to look into detailed intricacies of biological systems. It has provided an efficient and cost-effective approach with higher accuracy. The advent of microRNAs also known as small noncoding genes has begun the paradigm shift in oncological research. We are now able to profile expression profiles of RNAs using RNA-seq data. microRNA profiling has helped in uncovering their relationship in various genetic and biological processes. Here in this chapter, the authors present a review of the machine learning perspective in cancer research.

scholarly journals Subsequent Injury is Common after Foot and Ankle Surgery in Patients Receiving Workers’ Compensation

2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0017
Author(s):  
Gabrielle Bui ◽  
Phinit Phisitkul ◽  
Natalie Glass ◽  
Chris Cychosz ◽  
Sean Boarini
Keyword(s):  
Retrospective Chart Review ◽  
Anatomical Location ◽  
Workers Compensation ◽  
Foot And Ankle ◽  
Chi Square ◽  
Legal Representation ◽  
Increased Risk ◽  
Ankle Surgery ◽  
Poor Outcomes ◽  
Subsequent Injury

Category: Ankle Introduction/Purpose: Workers’ compensation (WC) has been associated with poor outcomes following a variety of injuries and surgeries. Previous studies have investigated surgical outcomes via satisfaction surveys, but rates of subsequent injury following surgery have not been specifically studied. The purpose of this study was to investigate the rates, locations and risk factors for subsequent injuries in WC patients and non-WC patients who underwent the same surgeries. Methods: With IRB approval, we identified the records of patients with a foot or ankle surgery performed by a single surgeon from 2009-2015. We included only surgeries with one of the most common current procedural terminology (CPT) codes from the WC population. A retrospective chart review was performed on all WC and non-WC patients with at least one of these CPT codes. A subsequent injury was defined as a new injury at a different anatomical location that occurred from 2 months to 2 years after the index surgery. Chi-square and two-tailed t-tests were used to compare WC and non-WC patient populations, and to determine factors associated with subsequent injuries. Results: Overall, the WC population had higher rates of subsequent injury than the non-WC population 23.21% versus 7.27%, p=.0011. Within the WC patient population, patients with subsequent injuries were older than patients without subsequent injuries 48.78±7.30 versus 41.58±12.40, p=.0137. In a blinded review of the charts and Iowa Courts Online, legal representation was found to be more common in WC patients with subsequent injuries than WC patients without subsequent injuries (76.92% versus 37.21%, p=.0240). In the non-WC population, there were more males in the group without subsequent injuries than in the group with subsequent injuries 42.48% versus 8.33%, p=.0287. There were no significant differences in locations of subsequent injury. Hip, knee and contralateral foot and ankle were common areas of subsequent injury in both groups. Conclusion: Overall, WC patients had higher rates of subsequent injury than non-WC patients. Within the WC group, legal representation further raised the risk of subsequent injury. Gender may mediate variable reporting of subsequent injuries in non-WC populations. While the reason for this increased risk of subsequent injury is not known, the differences are enough that they should be considered when counseling WC patients considering these surgeries. Additionally, if further study supported these findings, knowledge of the areas at risk for subsequent injury might lead to preventative strategies that could decrease the risk of subsequent injury.

scholarly journals Prognostic Impact of Tumor-Associated Macrophages on Survival Is Checkpoint Dependent in Classical Hodgkin Lymphoma

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 877 ◽  
Author(s):  
Kristiina Karihtala ◽  
Suvi-Katri Leivonen ◽  
Oscar Brück ◽  
Marja-Liisa Karjalainen-Lindsberg ◽  
Satu Mustjoki ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Digital Image Analysis ◽  
Tumor Tissue ◽  
Immune Escape ◽  
Clinical Impact ◽  
Prognostic Impact ◽  
Classical Hodgkin Lymphoma ◽  
Tissue Samples ◽  
Tumor Associated Macrophage ◽  
Poor Outcomes

Tumor microenvironment and immune escape affect pathogenesis and survival in classical Hodgkin lymphoma (cHL). While tumor-associated macrophage (TAM) content has been associated with poor outcomes, macrophage-derived determinants with clinical impact have remained undefined. Here, we have used multiplex immunohistochemistry and digital image analysis to characterize TAM immunophenotypes with regard to expression of checkpoint molecules programmed cell death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO-1) from the diagnostic tumor tissue samples of 130 cHL patients, and correlated the findings with clinical characteristics and survival. We show that a large proportion of TAMs express PD-L1 (CD68+, median 32%; M2 type CD163+, median 22%), whereas the proportion of TAMs expressing IDO-1 is lower (CD68+, median 5.5%; CD163+, median 1.4%). A high proportion of PD-L1 and IDO-1 expressing TAMs from all TAMs (CD68+), or from CD163+ TAMs, is associated with inferior outcome. In multivariate analysis with age and stage, high proportions of PD-L1+ and IDO-1+ TAMs remain independent prognostic factors for freedom from treatment failure (PD-L1+CD68+/CD68+, HR = 2.63, 95% CI 1.17–5.88, p = 0.019; IDO-1+CD68+/CD68+, HR = 2.48, 95% CI 1.03–5.95, p = 0.042). In contrast, proportions of PD-L1+ tumor cells, all TAMs or PD-L1− and IDO-1− TAMs are not associated with outcome. The findings implicate that adverse prognostic impact of TAMs is checkpoint-dependent in cHL.

Abstract 4551: Prognostic impact of GLUT-1 and Ki-67 expressions in early-stage lung adenocarcinomas

2012 ◽  
Author(s):  
Yuho Maki ◽  
Shinichi Toyooka ◽  
Koichi Ichimura ◽  
Junichi Soh ◽  
Kazuhiko Shien ◽  
...  
Keyword(s):  
Early Stage ◽  
Prognostic Impact ◽  
Ki 67 ◽  
Glut 1 ◽  
Lung Adenocarcinomas

Prognostic Significance of Angiogenesis and Ki-67, p53, and p21 Expression: A Population-Based Endometrial Carcinoma Study

1999 ◽  
Vol 17 (5) ◽  
pp. 1382-1382 ◽  
Author(s):  
Helga B. Salvesen ◽  
Ole Erik Iversen ◽  
Lars A. Akslen
Keyword(s):  
High Risk ◽  
Endometrial Carcinoma ◽  
Cox Regression ◽  
Figo Stage ◽  
Population Based ◽  
Prognostic Impact ◽  
Histologic Type ◽  
Ki 67 ◽  
Cox Regression Analysis

PURPOSE: For endometrial carcinoma patients, there is a need for improved identification of high-risk groups that may benefit from postoperative adjuvant therapy. We therefore studied the prognostic impact of markers for cell proliferation, cell-cycle regulation, and angiogenesis among endometrial carcinoma patients in a population-based setting. PATIENTS AND METHODS: All patients diagnosed with endometrial carcinoma between 1981 and 1985 in Hordaland County, Norway, were studied. The median follow-up for the survivors was 11.5 years (range, 8 to 15 years), with no patient lost because of insufficient follow-up information. Paraffin-embedded tumor tissue, available in 96% of the cases (n = 142), was studied immunohistochemically for microvessel density (MVD) and expression of Ki-67, p53, and p21 proteins. We used the hot spot method for calculation of MVD, and expression of Ki-67 and p21 protein, because this approach may increase the probability of detecting small aggressive clones of possible prognostic relevance. The importance of these tumor markers was investigated in univariate survival analyses and Cox regression analysis. RESULTS: The majority of traditional clinicopathologic variables was significantly associated with the tumor biomarkers. Age, International Federation of Gynecology and Obstetrics (FIGO) stage, histologic type, histologic grade, MVD, as well as Ki-67, p53, and p21 protein expression, all significantly influenced survival in univariate analyses (P ≤ .05). In the Cox regression analysis, age, FIGO stage, MVD, Ki-67 expression, and p53 expression were the only variables with independent prognostic impact (P ≤ .05), whereas histologic type, histologic grade, and p21 expression had no independent influence. A group of high-risk patients with more than one unfavorable marker was identified. CONCLUSION: In addition to age and FIGO stage, MVD, Ki-67, and p53 protein expression showed an independent prognostic impact. Thus, information derived from routine histologic specimens identified a subgroup of high-risk endometrial carcinoma patients in this population-based study.

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