Prognostic value of PD-1 and PD-L1 expression in patients with high-grade urothelial carcinoma of the upper urinary tract.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 358-358
Author(s):  
Laura-Maria Krabbe ◽  
Barbara Heitplatz ◽  
Ryan C Hutchinson ◽  
Solomon L Woldu ◽  
Sina Preuss ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Prognostic Value ◽  
Cox Regression ◽  
Tumor Infiltrating Lymphocytes ◽  
Tissue Microarrays ◽  
Tumor Stage ◽  
Survival Outcomes ◽  
High Grade ◽  
Cancer Specific Survival ◽  
Infiltrating Lymphocytes

358 Background: To investigate the prognostic value of PD-1 and PD-L1 expression in patients with high-grade upper tract urothelial carcinoma (UTUC). Methods: Tissue microarrays were created using 448 patients from the International UTUC collaboration who underwent extirpative surgery for high-grade UTUC and stained for PD-1 (antibody (AB): NAT105, diluted 1:250 from Ventana) and PD-L1 (AB: E1L3N prediluted from Cell Signaling). PD-1 and PD-L1 expression was assessed in a semi-quantitative fashion and any percentage of staining of the tumor cells (PD-L1) and tumor-infiltrating lymphocytes (PD-1) was considered positive. Univariate (UVA) and multivariate analyses (MVA) were performed to assess independent prognosticators of oncological outcomes. No funding was received. Results: Median age of the cohort was 69.2 years and 56.5% of patients were male. PD-L1 and PD-1 were positive in 24.1% and 37.5% of patients. PD-L1 positivity was associated with favorable pathological stage, where as PD-1 positivity was significantly associated with pelvicalyceal location, lymph node metastases, non-organ confined disease, presence of lymphovascular invasion, sessile architecture, necrosis, concomitant CIS, and history of non-muscle invasive bladder cancer. PD-L1 positivity was not significantly associated with survival outcomes. In Cox regression UVA, PD-1 positivity was associated with worse recurrence-free survival (RFS) (HR 1.5 (95%CI 1.08-2.14, p=0.016)), cancer-specific survival (CSS) (HR 1.5 (95%CI 1.07-2.19, p=0.021)), and overall survival (OS) (HR 1.5 (95%CI 1.10-1.97, p=0.009)). However in MVA, PD-1 positivity was not found to be an independent predictor of RFS, CSS or OS. Conclusions: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and was a significant prognosticator for RFS, CSS and OS on UVA in patients treated with extirpative surgery for high-grade UTUC in a large, multi-institutional cohort. In MVA, the independent prognostic value of PD-1 was not confirmed. PD-L1 positivity was associated with lower tumor stage, but not with other pathological characteristics or survival outcomes.

PD-L1 Expression and CD8+ Tumor-infiltrating Lymphocytes in Different Types of Tubo-ovarian Carcinoma and Their Prognostic Value in High-grade Serous Carcinoma

2020 ◽  
Vol 44 (8) ◽  
pp. 1050-1060
Author(s):  
Hao Chen ◽  
Kyle Molberg ◽  
Amanda L. Strickland ◽  
Diego H. Castrillon ◽  
Kelley Carrick ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Prognostic Value ◽  
Tumor Infiltrating Lymphocytes ◽  
Serous Carcinoma ◽  
High Grade ◽  
Different Types ◽  
Infiltrating Lymphocytes

Metabolic syndrome and upper tract urothelial carcinoma: A retrospective analysis from a large Chinese cohort.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 452-452
Author(s):  
Hang Xu ◽  
Ping Tan ◽  
Lu Yang ◽  
Qiang Wei
Keyword(s):  
Metabolic Syndrome ◽  
Urothelial Carcinoma ◽  
Prediction Models ◽  
Cox Regression ◽  
Density Lipoprotein ◽  
Upper Tract Urothelial Carcinoma ◽  
Survival Outcomes ◽  
Cancer Specific Survival ◽  
Cox Regression Analysis ◽  
Upper Tract

452 Background: Metabolic syndrome (MetS) has been reported to be associated with poor survival outcomes in cancer patients. However, the role of MetS in upper tract urothelial carcinoma (UTUC) has yet to be explored. We aim to investigate the prognostic value of MetS in UTUC after radical nephroureterectomy (RNU). Methods: A total of 644 patients with UTUC after RNU were identified at West China Hospital from May 2003 to December 2016. MetS was defined as the co-existence of three or more of five components (obesity, hypertension, elevated fasting glucose, decreased high-density lipoprotein-cholesterol and hypertriglyceridemia). Logistic and Cox regression analyses was performed to evaluate the associations of MetS with pathological features and survival outcomes. Decision curve analysis was performed to determine the clinical utility of the prediction models. Results: Of 644 patients, 157 (24.4%) had MetS. Over a median follow-up of 39 months, 269 (41.8%) experienced disease recurrence, 233 (36.2%) died and 185 (28.7%) died of UTUC. MetS was independently associated with high-grade disease (odds ratio [OR]: 2.01, P = 0.005), advanced pT stage (≥ pT3, OR: 1.54, P = 0.027) and lymphovascular invasion (OR: 1.71, P = 0.03). Multivariate Cox regression analysis showed that MetS was an independent factor for decreased cancer-specific survival (CSS, HR: 1.38, 95% CI: 1.01-1.89, P = 0.042) but not for RFS (HR: 1.27, 95% CI: 0.97-1.67, P = 0.078) and OS (HR: 1.24, 95% CI: 0.95-1.62, P = 0.121). The estimated c-index of the multivariate models for CSS was 0.763 compared with 0.769 when MetS added. Conclusions: MetS is a negative prognostic factor in UTUC. Further studies of MetS in UTUC are demanded.

Intratumoral Balance of Regulatory and Cytotoxic T Cells Is Associated With Prognosis of Hepatocellular Carcinoma After Resection

2007 ◽  
Vol 25 (18) ◽  
pp. 2586-2593 ◽  
Author(s):  
Qiang Gao ◽  
Shuang-Jian Qiu ◽  
Jia Fan ◽  
Jian Zhou ◽  
Xiao-Ying Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Cox Regression ◽  
Independent Predictor ◽  
Cytotoxic T Cells ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Tissue Microarrays ◽  
Kaplan Meier ◽  
Infiltrating Lymphocytes

Purpose To investigate the prognostic value of tumor-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in hepatocellular carcinoma (HCC) patients after resection. Patients and Methods CD3+, CD4+, CD8+, Foxp3-positive, and granzyme B-positive TILs were assessed by immunohistochemistry in tissue microarrays containing HCC from 302 patients. Prognostic effects of low- or high-density TIL subsets were evaluated by Cox regression and Kaplan-Meier analysis using median values as cutoff. Results CD3+, CD4+, CD8+ TILs were associated with neither overall survival (OS) nor disease-free survival (DFS). The presence of low intratumoral Tregs in combination with high intratumoral activated CD8+ cytotoxic cells (CTLs), a balance toward CTLs, was an independent prognostic factor for both improved DFS (P = .001) and OS (P < .0001). Five-year OS and DFS rates were only 24.1% and 19.8% for the group with intratumoral high Tregs and low activated CTLs, compared with 64.0% and 59.4% for the group with intratumoral low Tregs and high activated CTLs, respectively. Either intratumoral Tregs alone (P = .001) or intratumoral activated CTLs (P = .001) alone is also an independent predictor for OS. In addition, high Tregs density was associated with both absence of tumor encapsulation (P = .032) and presence of tumor vascular invasion (P = .031). Conclusion Tregs are associated with HCC invasiveness, and intratumoral balance of regulatory and cytotoxic T cells is a promising independent predictor for recurrence and survival in HCC. A combination of depletion of Tregs and concomitant stimulation of effector T cells may be an effective immunotherapy to reduce recurrence and prolong survival after surgery.

The prognostic role of tumor-infiltrating lymphocytes in urothelial carcinoma of bladder: A systematic review and meta-analysis

2020 ◽  
Author(s):  
Zhiqiang Yang ◽  
Yujin Bai ◽  
Xu Hu ◽  
Ping Han
Keyword(s):  
Systematic Review ◽  
Urothelial Carcinoma ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Cochrane Library ◽  
Prognostic Impact ◽  
Infiltrating Lymphocytes ◽  
Urothelial Carcinoma Of Bladder

Abstract Background: Tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment are associated with different prognosis in various malignancies. However, their prognostic impact remains controversial in urothelial carcinoma of bladder (UCB). In this systematic review and meta-analysis, we aimed to investigate the prognostic value of TILs in UCB patients.Methods: A systematic review and meta-analysis was performed using Pubmed, Embase and Cochrane Library. Studies were eligible if they investigated the prognostic value of CD3+, CD4+, CD8+, Foxp3+ lymphocytes or TILs in UCB patients, by time-to-event survival analysis. All studies were appraised for risk of bias using the Quality and Prognosis Studies (QUIPS) criteria. Hazard rations (HRs) with their 95% confidence interval (CIs) from each study were used to generate pooled HRs. Results: A total of 14 studies assessing the impact of TILs on prognostic outcomes in UCB patients were included in final analysis. The pooled analysis indicated a favorable role of CD3+ TILs (HR 0.74 (95% CI 0.62-0.88) for overall survival) and CD8+ TILs (HR 0.46 (95% CI 0.28-0.74) for OS) in the clinical outcomes of UCB, while Foxp3+ TILs were associated with worse survival (HR 2.21 (95% CI 1.47-3.32) for recurrence-free survival). Conclusions: This systematic review and meta-analysis confirmed the favorable prognostic impact of CD3+ and CD8+ tumor-infiltrating T cells in UCB patients and found the association between Foxp3+ TILs and worse survival. Future studies using large cohorts and standardized methodology with regard to tumor subsites, stages and treatment modalities are needed to incorporate TILs with clinical practice.

scholarly journals Tumor-infiltrating Lymphocytes Expression in Stage IIIc/IV of High-grade Serous Ovarian Cancer: Variation with Neoadjuvant Chemotherapy and Prognostic Value

Oncogen ◽  
2019 ◽  
Vol 2 (2) ◽  
Author(s):  
K Rojas ◽  
G Prado-Vazquez ◽  
C Barcena ◽  
L Trilla-Fuertes ◽  
A Gamez-Pozo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Prognostic Value ◽  
Tumor Infiltrating Lymphocytes ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Stage Iiic ◽  
Infiltrating Lymphocytes

scholarly journals Impact of cachexia on oncologic outcomes of sarcopenic patients with upper tract urothelial carcinoma after radical nephroureterectomy

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250033
Author(s):  
Hao-Wei Chen ◽  
Yu-Chen Chen ◽  
Li-Hwa Yang ◽  
Ming-Chen Paul Shih ◽  
Ching-Chia Li ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Cox Regression ◽  
Medical Center ◽  
Prognostic Significance ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Oncologic Outcomes ◽  
Radical Nephroureterectomy ◽  
Cancer Specific Survival ◽  
Poor Prognostic Factor

Objectives To investigate the prognostic significance of sarcopenic cachexia compared to sarcopenia without cachexia in the outcomes of upper urinary tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU). Materials and methods Between 2011 and 2016, 163 patients with UTUC who received RNU at a tertiary medical center were included. Pre-operatively clinical data, history, and abdominal computer tomography scans were analyzed retrospectively. The diagnosis of sarcopenia was based on abdominal computed tomography data on the patient’s skeletal muscles. Outcomes of relapse-free, cancer-specific, and overall survival were analyzed by multivariate Cox regression. Results After adjusting for age, sex, pre-operatively estimated glomerular filtration rate, body mass index, underlying diseases, tumor grade, and tumor stage, cachexia was a significant poor prognostic factor for relapse-free survival (hazard ratio [HR]: 18.5, 95% confidence interval [CI]: 2.87–118, p = 0.002) and cancer-specific survival (HR: 26.6, 95% CI: 4.04–175, p = 0.001). In contrast, sarcopenia without cachexia was not a significant predictor of cancer outcomes. Conclusions To date, this is the first study to investigate the effect of cachexia among sarcopenic patients with UTUC treated with RNU. We identified the prognostic significance of cachexia on outcomes. Indeed, when UTUC is treated with RNU, we should evaluate not only sarcopenia status but also cachexia. The low survival rate among patients with UTUC complicated with cachexia deserves attention.

Prognostic Value of Natural Killer Cells Besides Tumor-Infiltrating Lymphocytes in Breast Cancer Tissues

2021 ◽  
Author(s):  
Lobna Bouzidi ◽  
Hana Triki ◽  
Slim Charfi ◽  
Wala Ben Kridis ◽  
Mohamed Derbel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Prognostic Value ◽  
Tumor Infiltrating Lymphocytes ◽  
Killer Cells ◽  
Cancer Tissues ◽  
Infiltrating Lymphocytes

scholarly journals Mismatch repair deficiency is associated with specific morphologic features and frequent loss of ARID1A expression in ovarian clear cell carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Huijuan Ge ◽  
Yaoxin Xiao ◽  
Guangqi Qin ◽  
Yanzi Gu ◽  
Xu Cai ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Tumor Infiltrating Lymphocytes ◽  
Tissue Microarrays ◽  
Ovarian Clear Cell Carcinoma ◽  
Repair Deficiency ◽  
Ovarian Epithelial Carcinoma ◽  
Histological Characteristics ◽  
Infiltrating Lymphocytes

Abstract Background Ovarian clear cell carcinoma (OCCC) is the second subtype of ovarian epithelial carcinoma reported to be closely related to Lynch syndrome (LS). ARID1A mutation is an important pathogenetic mechanism in OCCC that leads to loss of ARID1A expression in approximately half of OCCCs. However, the correlation of MMR status and ARID1A deficiency is unclear. The current study aimed to identify the clinical and histopathological characteristics of OCCC associated with dMMR and to further explore the association between dMMR and ARID1A deficiency. Methods A cohort of 176 primary OCCC patients was enrolled and review included histological characteristics (nuclear atypia, necrosis, mitosis, stromal hyalinization, and background precursors) and host inflammatory response (tumor-infiltrating lymphocytes, peritumoral lymphocytes, intratumoral stromal inflammation and plasma cell infiltration). Immunohistochemical staining of MLH1, PMS2, MSH2, MSH6 and ARID1A was performed using tissue microarrays. Results dMMR was detected in 10/176 tumors (6 %), followed by MSH2/MSH6 (6/176), MLH1/PMS2 (3/176), and MSH6 (1/176). The average age of patients with dMMR was younger than that of patients with intact MMR (46 y vs. 53 y). Tumors with diffuse intratumoral stromal inflammation remained significantly associated after multivariate analysis. ARID1A expression was absent in 8 patients with dMMR (8/10), which is a significantly higher frequency than that observed in patients with intact MMR (80 % vs. 43.2 %). Conclusions Our study indicates that diffuse intratumoral stromal inflammation of OCCCs is associated with dMMR, with loss of MSH2/MSH6 expression being most frequent. dMMR is strongly associated with the loss of ARID1A expression in OCCC.

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