scholarly journals Differential Characteristics and Prognosis of PD-L1–Positive Endometrial Carcinomas: A Retrospective Chart Review

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1047
Author(s):  
Justin Z. Amarin ◽  
Razan Mansour ◽  
Sura Al-Ghnimat ◽  
Maysa Al-Hussaini
Keyword(s):  
Overall Survival ◽  
Tumor Cells ◽  
Chart Review ◽  
Prognostic Significance ◽  
Retrospective Chart Review ◽  
Cancer Center ◽  
High Grade ◽  
Endometrial Carcinomas

Women with endometrial carcinomas that express PD-L1 may respond better to immunotherapy. Our aim was to investigate the differential characteristics of PDL1–positive endometrial carcinomas and the prognostic significance of PDL1. We performed a retrospective chart review of 231 women with endometrial carcinomas who were managed at King Hussein Cancer Center (2007–2016) and performed immunohistochemistry for MLH1, PMS2, MSH2, MSH6, p53, and PD-L1. Overall, 89 cases (38.5%) were MMR-deficient. PD-L1 was expressed in 49 cases (21.2%) and its expression was significantly associated with MLH1/PMS2 deficiency (p = 0.044) but not MSH2/MSH6 deficiency (p = 0.59). p53 was mutant in 106 cases (46.5%), and its mutation was significantly associated with MMR proficiency (p < 0.001) but not PDL1 expression (p = 0.78). In women with endometrioid adenocarcinomas, PD-L1 expression was significantly associated with the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) grade (p = 0.008). Overall, PDL1 expression did not significantly predict overall survival in unadjusted or adjusted analyses (p = 0.92 and 0.54, respectively). In conclusion, tumors with MLH1/PMS2 loss and high-grade endometrioid adenocarcinomas were more likely to express PDL1 in tumor cells. Further research is required to investigate whether the presence of either characteristic signals a higher likelihood of a favorable response if immunotherapy is administered.

scholarly journals CD44 and CD24 Expression and Prognostic Significance in Canine Mammary Tumors

2018 ◽  
Vol 56 (3) ◽  
pp. 377-388 ◽  
Author(s):  
Bernadette Rogez ◽  
Quentin Pascal ◽  
Audrey Bobillier ◽  
François Machuron ◽  
Chann Lagadec ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Significance ◽  
Mammary Tumors ◽  
Clinicopathological Parameters ◽  
Tumor Type ◽  
High Grade ◽  
Mammary Carcinomas ◽  
Canine Mammary Tumors ◽  
Valuable Marker ◽  
High Level

CD44+/CD24– phenotype has been used to identify human and canine mammary cancer stem-like cells. In canine mammary tumors, CD44+/CD24– phenotype has been associated with high grade and lymph node infiltration. However, several studies have reported opposing results regarding the clinical significance of phenotypic groups formed by the combination of CD44 and CD24 in both human and canine mammary tumors. So far, no study has investigated the correlation between these phenotypes and survival in dogs. The aim of this study was to investigate the expression and distribution of CD44 and CD24 in canine mammary carcinomas and to correlate them with histological diagnosis and survival in a well-characterized cohort. Immunohistochemistry was performed in 96 mammary carcinomas with antibodies against CD44 and CD24. Expression of CD44+ and CD44+/CD24– phenotype was detected in 75 of 96 (78%) and 63 of 96 (65.6%) carcinomas, respectively. Their expression was associated with tumor type, occurring more often in tubular complex carcinomas than in solid carcinomas. CD44+/CD24– phenotype was associated with a better overall survival ( P = .001). CD24+ expression was detected in 52 of 96 tumors (54%) and CD44–/CD24+ phenotype in 39 of 96 tumors (40.6%). Both were associated with poor clinicopathological parameters (high grade, and emboli). No correlation with overall survival was observed. CD44+/CD24– expression was associated with a better prognosis and occurred at high frequency and high level, indicating that this phenotype is not suitable to detect cancer stem cells in canine mammary carcinomas. Although further studies are needed, our results suggest that CD24 may constitute a valuable marker of poor prognosis for canine mammary carcinomas.

scholarly journals High PD-L1 Expression on Tumor Cells Indicates Worse Overall Survival in Advanced Oral Squamous Cell Carcinomas of the Tongue and the Floor of the Mouth but Not in Other Oral Compartments

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1132
Author(s):  
Łukasz Jan Adamski ◽  
Anna Starzyńska ◽  
Paulina Adamska ◽  
Michał Kunc ◽  
Monika Sakowicz-Burkiewicz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Oral Cavity ◽  
Tumor Cells ◽  
Squamous Cell ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Lower Percentage ◽  
Interleukin 33 ◽  
Impact On Survival

The markers of the tumor microenvironment (TME) are promising prognostic and predictive factors in oral squamous cell carcinoma (OSCC). The current study aims to analyze the immunohistochemical expression of programmed cell death-ligand 1 (PD-L1) and interleukin-33 (IL-33) in a cohort of 95 chemonaïve OSCCs. PD-L1 and IL-33 were assessed separately in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs). High PD-L1 expression in TILs was associated with better overall survival (OS) in univariate analysis. Tumors localized in the floor of the oral cavity and tongue tended to have a lower percentage of PD-L1-positive TCs when compared to other locations. PD-L1 expression on TCs had no prognostic significance when the whole cohort was analyzed. However, along with the T descriptor (TNM 8th), it was included in the multivariable model predicting death in carcinomas of the floor of the oral cavity and tongue (HR = 2.51, 95% CI = 1.97–5.28). In other locations, only nodal status was identified as an independent prognostic factor in multivariate analysis (HR = 0.24, 95% CI = 0.08–0.70). Expression of IL-33 had no impact on survival, but it was differently expressed in various locations. In conclusion, the prognostic significance of PD-L1 in oral cancer depends on the tumor site and type of cell expressing immune checkpoint receptor (TCs vs. TILs).

scholarly journals Incidence and Prognostic Significance of PD-L1 Expression in High-Grade Salivary Gland Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Qigen Fang ◽  
Yao Wu ◽  
Wei Du ◽  
Xu Zhang ◽  
Defeng Chen
Keyword(s):  
Salivary Gland ◽  
Tumor Cells ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
High Grade ◽  
Salivary Gland Carcinoma ◽  
Gland Carcinoma ◽  
The Difference

ObjectivePD-L1 is one of the predictors of immunotherapy efficacy. Our goal was to analyze its expression and prognostic significance in high-grade salivary gland carcinoma (SGC).MethodsPD-L1 expression was evaluated using paraffin-embedded specimens from patients with surgically treated high-grade SGC, and it was scored by the tumor proportion score (TPS), combined positive score (CPS), and immune cell (IC) score. Associations between clinicopathological variables, disease-free survival (DFS), overall survival (OS) and PD-L1 expression were assessed.ResultsTPS≥1% occurred in 47 patients with an incidence of 43.1%, and it was significantly related to an advanced tumor stage. In patients with TPS&lt;1%, TPS ranging from 1% to 20%, and TPS≥20%, the 5-year DFS rates were 36%, 26%, and 13%, respectively, and the difference was significant. In patients with TPS&lt;1%, TPS ranging from 1% to 20%, and TPS≥20%, the 5-year OS rates were 49%, 24%, and 13%, respectively, and the difference was significant. CPS≥1 occurred in 87 patients with an incidence of 79.8%. IC scores of 0, 1, 2, and 3 were noted in 24 (22.0%), 37 (33.9%), 31 (28.4%), and 17 (15.6%) patients, respectively. Both CPS and IC scores had no impact on DFS or OS.ConclusionsThe expression of PD-L1 in tumor cells of high-grade SGCs was not uncommon, and it was significantly associated with tumor stage. PD-L1 expression in tumor cells rather than in immune cells indicated a poor prognosis.

Documentation of medical marijuana use in cancer patients

2019 ◽  
Vol 26 (5) ◽  
pp. 1117-1127 ◽  
Author(s):  
Jessica N LeClair ◽  
Kevin W Chamberlin ◽  
Jessica Clement ◽  
Lisa M Holle
Keyword(s):  
Quality Improvement ◽  
Cancer Patients ◽  
Chart Review ◽  
Medical Marijuana ◽  
Retrospective Chart Review ◽  
Marijuana Use ◽  
Cancer Center ◽  
Medication List ◽  
Post Test ◽  
Medical Marijuana Use

Purpose Medical marijuana is often used as adjuvant therapy in cancer patients for symptom management, although limited evidence-based studies evaluating its efficacy or safety exist. Similar to over-the-counter medications, supplements, or herbal products, documentation of medical marijuana is important to monitor efficacy, potential adverse effects, or interactions. The objective of this quality improvement study was to improve the consistency of medical marijuana documentation in cancer patients by assessing current practices; educating healthcare team members about the importance of documentation and newly established documentation process; and evaluating the new documentation process. Methods This three-part quality improvement study was approved by the Institutional Review Board. In part I, a voluntary survey was sent via email to Cancer Center healthcare personnel to assess the current documentation process of medical marijuana. In part II, a best practice process for documenting medical marijuana in the electronic medical record was established. Medical marijuana was to be listed as a historical medication in the medication list. In-person and electronic education sessions were offered to Cancer Center clinical staff. The education emphasized the importance of documenting medical marijuana use and provided a detailed process for electronic medical record documentation. A pre- and post-test to assess understanding was also included. Part III was a retrospective chart review to evaluate documentation practices of certified medical marijuana users in the Cancer Center. Patients included in the study were greater than 18 years old and certified for medical marijuana use on or after 1 January 2018. Department of Corrections patients were excluded. Descriptive statistics were used for data analysis. Results The survey results in part I demonstrated a lack of consistency in the documentation of medical marijuana in the Cancer Center. The pre- and post-test scores measured in part II showed a significant improvement in understanding after education was provided. The average pre-test score was a 61 and post-test score was 88, indicating an average increase of 27 points. A larger increase in test scores was observed in those attending the in-person education than the online sessions ( p < 0.002). The results of the retrospective chart review in part III revealed 56 patients who met inclusion criteria, but only 39 patients were alive and evaluated at the time of the retrospective chart review. Of the 39 patients, 22 never completed the patient registration process and therefore, would never have been able to obtain medical marijuana. Seven patients had medical marijuana properly documented in their medication list and 10 patients were missing documentation in the medication list, showing room for improvement in documentation practices. Conclusions This quality improvement study led to the implementation of medical marijuana documentation in the medication list. Education increased healthcare team members understanding of medical marijuana utilization and the importance of documentation.

HLA Homozygosity and Haplotype Bias Among Patients with Chronic Lymphocytic Leukemia: Implications for Disease Control by Physiologic Immune Surveillance

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1370-1370
Author(s):  
Nina Shah ◽  
William Decker ◽  
Ruth Lapushin ◽  
Dongxia Xing ◽  
Simon Robinson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcome ◽  
Patient Population ◽  
Research Funding ◽  
Advanced Disease ◽  
Immune Surveillance ◽  
Prognostic Significance ◽  
Cancer Center ◽  
Cell Transplant ◽  
Hla Alleles

Abstract Abstract 1370 Background: Though the cancer immune surveillance hypothesis was first proposed a century ago, there has been limited evidence to support the role of antigen presentation in the detection or suppression of CLL. In this study we evaluated the frequencies of HLA haplotype and homozygosity and subsequent impact on clinical outcome in CLL patients with advanced disease. Methods: We performed a retrospective chart review of 249 CLL patients who were referred for allogeneic stem cell transplant at MD Anderson Cancer Center. We compared HLA allele frequencies of the patient population with those of local, race-matched controls and identified specific HLA alleles which were more frequent in the patient population. We also compared HLA homozygosity between the patient and control population. The Kaplan-Meier method was then used to determine the prognostic significance of the identified HLA alleles and homozygosity on clinical outcome within our patient population. Progression-free survival (PFS) was calculated from the time of first treatment to the time of progression or death. Results: CLL patients with advanced disease were significantly more likely to express HLA-A1 (OR=1.49, 95% CI 1.15–1.94, p=0.0003) or HLA- C7 (OR 1.24, 95% CI 1.00–1.53, p=0.05). In addition, these patients were more likely to be homozygous at any HLA locus than were controls (OR=1.20, 95% CI 0.97–1.48, p=0.04), particularly at HLA-C (OR=1.62, 95% CI 1.13–2.33, p=0.002) and at multiple HLA loci (OR=1.69, 95% CI 1.06–2.70, p=0.006). CLL patients who were HLA-A1+, HLA-A1/C7+ or homozygous at any allele demonstrated worse PFS in comparison with CLL patients without any of these HLA allelic characteristics. Median survival was 23.9 months for HLA-A1+ patients, 13.9 months for HLA-A1/C7+ patients and 25.7 months for patients with homozygosity, in comparison to 31.8 months for the population without any detrimental alleles or homozygosity (p=0.02, p=0.0008, and p=0.007 respectively, Figure 1: A, B, C). Analysis of patients possessing only HLA-C7 as a risk factor demonstrated a trend toward decreased PFS but was not quite statistically significant (p=0.07, data not shown). Conclusions: Patients with advanced CLL appear to express certain HLA alleles and exhibit HLA homozygosity more frequently than normal controls. In addition, these HLA characteristics may predispose CLL patients to a worse outcome. Because HLA allelic variation determines the specificity of antigens presented to the immune system, the data suggest that immune surveillance may play a physiologic role in the control of leukemic disease and provide a theoretical framework for the identification of CLL antigens which could eventually serve as targets for immunotherapy. A. Negative effects of HLA-A1 allele on overall survival of patients with advanced CLL are B. synergistically worsened by the presence of the HLA-C7 allele. C. Homozygosity at any HLA allele also imparted a negative impact upon overall survival. Disclosures: O'Brien: Novartis: Research Funding; BMS: Research Funding.

Incidence and characterization of pure non-urothelial bladder and upper tract cancers: A 10-year review.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 414-414
Author(s):  
Kanika Gupta ◽  
Ehab El Bahesh ◽  
Antoine Nafez Finianos ◽  
Brandon Clark ◽  
Samuel Simmens ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Randomized Clinical Trials ◽  
Retrospective Chart Review ◽  
The United States ◽  
Primary Treatment ◽  
Treatment Modalities ◽  
Cancer Center ◽  
Favorable Histology

414 Background: Bladder cancer is the sixth most common malignancy in the United States. Urothelial carcinoma makes up 90% of bladder cancer histology, which may be pure or mixed. It includes adenocarcinoma (Ad), squamous (SqC), glandular, sarcomatoid (St), micropapillary, small cell (SC) and plasmacytoid variants. Pure non-urothelial cancers have worse overall survival compared to urothelial cancer with mixed histologic features. However, little research has been done to characterize pure non-urothelial histologies, and there are no randomized clinical trials evaluating treatment modalities for non-urothelial cancers. This retrospective study characterizes pure non-urothelial cancers and their treatments. Methods: A retrospective chart review of the last 10 years was performed using data from the George Washington University Cancer Center Tumor Registry Data. Statistical analysis was done using the Fisher’s test and Kaplan-Meier survival curves. Results: Out of 449 consecutive patients with bladder cancers, 19 patients had pure non-urothelial carcinoma (4.2%): 7 SqC, 6 Ad, 3 SC, 2 lymphoma (Ly), and 1 St. SqC and Ad were more likely than SC to be diagnosed at an advanced stage (p = 0.04), with median age of diagnosis at 53.5 years for Ad, 68 years for SC and 69 years for Sq. None of the SC metastasized. Primary treatment for 94% of patients was a surgical intervention (9 TURBT, 2 partial cystectomy, 2 radical cystectomy, and 2 nephroureterectomy); 1 received neoadjuvant therapy. 11 patients received adjuvant chemotherapy – 7 with gemcitabine-based regimens and 10 with platinum-based regimens. While not statistically significant, median overall survival varied – 404 days for Ad, 213 days for SqC, and 1567 days for SC. Conclusions: SC was a more favorable histology when compared to SqC or Ad, presenting at an earlier stage with lower incidence of metastasis that perhaps reflected the improved overall survival. Identifying patients with more aggressive disease earlier allows for the potential role for more aggressive therapies that may result in improved outcomes. While the sample size is small, it identifies characteristics and potential differences between bladder cancer with rare histologies.

Effect of age and ethnicity on the tumor location, nuclear accumulation of p53 and clinical outcome in colorectal adenocarcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 559-559
Author(s):  
Ravi Kumar Paluri ◽  
Michael Behring ◽  
James Posey ◽  
Upender Manne
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Tumor Location ◽  
Genetic Alterations ◽  
Proximal Colon ◽  
Nuclear Accumulation ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Race Ethnicity

559 Background: The race/ethnicity based research in colorectal cancer (CRC) care continues to remain a high priority in developing personalized medicine, and to improve overall clinical outcomes. The role of p53 abnormalities in prognostication of CRC has been evaluated earlier. The incidence of nuclear accumulation of p53 (p53nac) and its prognostic relevance in African American (AA) and non-Hispanic white patients (pts) have been investigated, and it was suggested that the clinical consequences of p53nac in CRC varies with anatomic location of the tumor and the race of the patient. However, the clinical value of p53nac in relation to age, the tumor location, and race together is not assessed. Thus, we evaluated prognostic significance of p53nac by considering the tumor location, age, race/ethnicity and p53nacin CRCs in AA and white pts. Methods: Formalin fixed paraffin embedded CRC tissues from 242 AAs and 346 whites who underwent surgery were assessed for p53nac by routine immunohistochemistry (IHC). The routine (not antigen retrieval) IHC will identify the majority of genetic alterations ( > 95% missense point mutations) and have significant association with patient survival in CRC. The association between phenotypes, p53nac status, clinicopathologic features, and overall survival were evaluated using the x2 test and Cox regression analyses. Results: Approximately equivalent proportions of distal (52%) and proximal adenocarcinomas (48%) were positive for p53nac in AA pts. In contrast, distal CRC from whites more frequently were positive for p53nac than from the proximal colon (67% vs. 34%, x2 P = 0.006). p53nac was found to be a strong predictor of poor overall survival in young ( < 65 yr) white pts with proximal tumors [hazard ratio (HR) = 2.8, 95% Confidence Intervals (CI):1.2-6.4] but not in AAs (HR = 0.7, 95% CI: 0.41-1.21). Conclusions: The findings of this study suggest that p53nac is a strong prognostic marker for young white pts with proximal colon adenocarcinomas. Our findings are clinically relevant because several small-molecule inhibitors of mutant p53 are under investigation. These studies were supported by a pilot project grant by the UAB Comprehensive Cancer center.

Tumor-collagen digital proximity signature to indicate prognosis in diffuse large B-cell lymphoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19073-e19073
Author(s):  
Talha Qaiser ◽  
Matthew Pugh ◽  
Sandra Margielewska ◽  
Robert Hollows ◽  
Paul Murray ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Cell ◽  
B Cell ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Automated Image Analysis ◽  
Large B Cell Lymphoma ◽  
Large B Cell

e19073 Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous tumor that originates from normal B-cells. Despite the use of combination chemotherapy, around 40% of DLBCL patients die (de Jonge, et al. European Journal of Cancer, 2016). Limited studies have investigated the role of collagen in the acellular tumor microenvironment. In this study, we present a novel digital signature of the proximity of tumor cells and collagen-VI (COL6) that can predict overall survival (OS) in DLBCL patients. To the best of our knowledge, this is the first study of its kind to employ automated image analysis. Methods: The proposed digital proximity signature (DPS) aggregates summary-level statistics from the entire whole slide image (WSI) and serves as a marker of regions, categorizing weak, moderate, significant, and strong tumor-collagen proximity and can be described as a surrogate for signaling. To accomplish this, we developed a novel artificial intelligence (AI) based multi-task model for simultaneous detection and classification of tumor cells and another bespoke method for automatically identifying COL6 fiber. The tumor-collagen proximity analysis was then performed by aggregating tumor cell statistics within the vicinity of COL6 fibres. Finally, the prognostic significance of DPS for OS in DLBCL was investigated with Kaplan-Meier analysis, stratifying patients into two groups based on the median of the DPS values. Results: We took WSIs of DLBCL tissue slides for 32 cases immunohistochemically stained with COL6 and Hematoxylin counterstain. The AI model for tumor cell identification achieved a high F1-score of 0.84, outperforming recent single-task learning models. Our results show that strong proximity of COL6 and tumor cells is linked to better OS in DLBCL patients ( p = 0.03). Conclusions: Our novel digitally computed COL6-tumor proximity signature shows prognostic significance for overall survival on a pilot dataset of 32 DLBCL patients. We are further validating the utility of this novel signature as a prognostic biomarker in larger cohorts of DLBCL patients.

scholarly journals A Comparison of Three Methods for the Detection of Circulating Tumor Cells in Patients with Early and Metastatic Breast Cancer

2017 ◽  
Vol 44 (2) ◽  
pp. 594-606 ◽  
Author(s):  
Eleni Politaki ◽  
Sofia Agelaki ◽  
Stella Apostolaki ◽  
Dora Hatzidaki ◽  
Areti Strati ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Prognostic Significance ◽  
Metastatic Breast ◽  
Double Immunofluorescence ◽  
First Line ◽  
Detection Rates ◽  
Line Chemotherapy

Background: We directly compared CTC detection rates and prognostic significance, using three different methods in patients with breast cancer (BC). Methods: Early (n=200) and metastatic (n=164) patients were evaluated before initiating adjuvant or first-line chemotherapy, using the CellSearchTM System, an RT-qPCR for CK-19 mRNA detection and by double immunofluorescence (IF) microscopy using A45-B/B3 and CD45 antibodies. Results: Using the CellSearchTM System, 37% and 16.5% of early BC patients were CTC-positive (at ≥1 and ≥2 CTCs/23 ml of blood), 18.0% by RT-qPCR and 16.9% by IF; no agreement was observed between methods. By the CellSearchTM 34.8% and 53.7% (at≥ 5 and ≥ 2 CTCs/7.5 ml) of metastatic patients were CTC-positive, 37.8% by RT-qPCR and 28.5% by IF. A significant agreement existed only between the CellSearchTM and RT-qPCR. In 60.8% of cases, differential EpCAM and CK-19 expression on CTCs by IF could explain the discrepancies between the CellSearchTM and RT-qPCR. CTC-positivity by either method was associated with decreased overall survival in metastatic patients. Conclusion: A significant concordance was observed between the CellSearchTM and RT-qPCR in metastatic but not in early BC. Discordant results could be explained in part by CTC heterogeneity. CTC detection by all methods evaluated had prognostic relevance in metastatic patients.

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