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).

Lack of Expression of Galectin-3 Is Associated With a Poor Outcome in Node-Negative Patients With Laryngeal Squamous-Cell Carcinoma

2002 ◽  
Vol 20 (18) ◽  
pp. 3850-3856 ◽  
Author(s):  
Mauro Piantelli ◽  
Stefano Iacobelli ◽  
Giovanni Almadori ◽  
Manuela Iezzi ◽  
Nicola Tinari ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Node Negative ◽  
Increased Risk ◽  
Galectin 3

PURPOSE: Galectin-3 is a pleiotropic carbohydrate-binding protein participating in a variety of normal and pathologic processes, including cancer progression. This study was aimed at evaluating the prognostic value of galectin-3 expression in node-negative laryngeal squamous-cell carcinoma (SCC). PATIENTS AND METHODS: Galectin-3 expression was analyzed by immunohistochemistry using M3/38 monoclonal antibody, in a single-institution series of 73 node-negative laryngeal SCC patients (median follow-up, 52 months; range, 2 to 90 months). RESULTS: Forty-two (57.5%) of 73 patients expressed galectin-3. Galectin-3 expression was positively associated with tumor keratinization and histologic grade. A significant correlation was found between galectin-3 tumor positivity and longer relapse-free and overall survival. In univariate analysis, high-grade (grade 3 or 4) tumors, nonkeratinizing tumors, and galectin-3–negative tumors showed a significantly increased risk of relapse and death. In multivariate analysis, only galectin-3 expression retained an independent prognostic significance for both relapse-free and overall survival. CONCLUSION: We conclude that the absence of galectin-3 expression is an independent negative prognostic marker in laryngeal SCC patients. Thus, histochemical detection of galectin-3 in these tumors could be useful for the selection of node-negative patients with potentially unfavorable outcomes, to establish adjuvant therapy protocols.

Combination of tumor multinucleation and spatial arrangement of tumor-infiltrating lymphocytes to predict overall survival in oropharyngeal squamous cell carcinoma: A multisite study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6566-6566
Author(s):  
Can Koyuncu ◽  
Germán Corredor ◽  
Cheng Lu ◽  
Paula Toro ◽  
Kaustav Bera ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Spatial Arrangement ◽  
Risk Scores ◽  
Infiltrating Lymphocytes

6566 Background: Oropharyngeal squamous cell carcinoma patients can have major morbidity from current treatment regimens, necessitating accurate identification of patients with aggressive versus indolent tumors. In this study, we sought to evaluate whether the combination of computer extracted features of tumor cell multinucleation (MN) and spatial interplay of tumor-infiltrating lymphocytes (TILs) is prognostic of overall survival (OS) in OPSCC patients. Methods: OPSCC specimens from 688 patients were retrospectively collected from 3 different sites. 141 patients from site 1 formed the training set (D1) and 322 patients from site 2 and 225 patients from site 3 formed the independent validation cohort (D2, n = 547). A machine learning (ML) model was employed to automatically calculate a Multi-nucleation risk index (MNI), which is the ratio of the number of MN to the number of epithelial cells, to each patient. A separate ML model was also used to capture measurements related to the interplay between TILs and tumor cells (SpaTIL), which were then used to compute a risk score using a Cox regression model. The median value of both the MNIs and the SpaTIL risk scores in D2 were used to identify patients as either low- or high-risk. A definitive label was assigned to each patient by combining the class labels obtained from the MNI and SpaTIL models using a logical AND operation. Results: In D2, the patients with high-risk scores had statistically significantly worse survival in univariate analysis. The univariate analysis yielded an HR = 1.91 (95% CI: 1.25-2.93, p = 0.0027) for D. Multivariate analysis controlling the effect of different clinical variables is shown in the table. Conclusions: We presented a computational pathology approach to prognosticate disease outcome in OPSCC by combining features relating to density of multinucleation and spatial arrangement of TILs and validated the approach on a large multi-site dataset. With additional validation the approach could potentially help identify OPSCC patients who could benefit from de-escalation of therapy. [Table: see text]

scholarly journals Overexpression of an Immune Checkpoint (CD155) in Breast Cancer Associated with Prognostic Significance and Exhausted Tumor-Infiltrating Lymphocytes: A Cohort Study

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Yu-Chen Li ◽  
Quan Zhou ◽  
Qing-Kun Song ◽  
Rui-Bin Wang ◽  
Shuzhen Lyu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cohort Study ◽  
Tumor Cells ◽  
Immune Checkpoint ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Immune Microenvironment ◽  
Infiltrating Lymphocytes ◽  
Low Expression

Purpose. The immune checkpoint inhibitor is approved for breast cancer treatment, but the low expression of PD-L1 limits the immunotherapy. CD155 is another immune checkpoint protein in cancers and interacts with ligands to regulate immune microenvironment. This study is aimed at investigating the expression of CD155 and the association with prognosis and pathological features of breast cancer. Methods. 126 patients were recruited this cohort study consecutively, and CD155 expression on tumor cells was detected by immunohistochemistry. The Kaplan-Meier survival curve and Cox hazard regression model were used to estimate the association. Results. 38.1% patients had an overexpression of CD155, and the proportion of tumor cells with CD155 overexpression was 17%, 39%, 37%, and 62% among Luminal A, Luminal B, HER2-positive, and triple negative breast cancer cases, respectively (p<0.05). Patients with CD155 overexpression had the Ki-67 index significantly higher than that of patients with low expression (42% vs. 26%). Though the number of tumor-infiltrating lymphocytes was higher among patients with CD155 overexpression (144/HPF vs. 95/HPF), the number of PD-1+ lymphocytes was significantly higher (52/HPF vs. 25/HPF, p<0.05). Patients of CD155 overexpression had the disease-free and overall survival decreased by 13 months and 9 months, respectively (p<0.05). CD155 overexpression was associated with an increased relapse (HR=13.93, 95% CI 2.82, 68.91) and death risk for breast cancer patients (HR=5.47,1.42,20.99). Conclusions. Overexpression of CD155 was correlated with more proliferative cancer cells and a dysfunctional immune microenvironment. CD155 overexpression introduced a worse relapse-free and overall survival and might be a potential immunotherapy target for breast cancer.

Prognostic Significance of CD4+and CD8+T Cell Infiltration Within Cancer Cell Nests in Vulvar Squamous Cell Carcinoma

2011 ◽  
Vol 21 (4) ◽  
pp. 717-721 ◽  
Author(s):  
Jacek Jan Sznurkowski ◽  
Anton Żawrocki ◽  
Janusz Emerich ◽  
Wojciech Biernat
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Cancer Cell ◽  
Squamous Cell ◽  
Immune Reaction ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Vulvar Squamous Cell Carcinoma

Background:The clinicopathological significance of the local spontaneous immune reaction in vulvar squamous cell carcinoma remains unclear. The purpose of this study was to clarify the role of the subtypes of tumor-infiltrating lymphocytes, both individually and synergistically.Methods:Seventy-six patients with verified histopathological data and complete clinical history were included into the study. We collected 76 paraffin-embedded samples of the primary tumor. The presence of CD4+and CD8+T cells was evaluated by immunohistochemistry and compared with commonly recognized prognostic factors. The primary end point analyzed was the overall survival.Results:CD4+and CD8+T cells were detected both within the nests of carcinoma and in the stroma, but only the infiltration within cancer cell nests was further analyzed. There was significant positive correlation (Spearman rho testR= 0.282,P= 0.014) between the number of intratumoral CD4+and CD8+T cells. No correlation was observed between the number of tumor-infiltrating CD4+and CD8+T cells and the patients' survival. Patients were classified into the following 4 groups (CD4+/CD8+, CD4−/CD8−, CD4+/CD8−, CD4−/CD8+), but none of them correlated with overall survival.Conclusions:These data support the statement that CD4+and CD8+T cells cooperate within cancer cell nests, but this spontaneous immune reaction is an individual feature not influencing the prognosis. Intratumoral CD4+T cells might control or reflect the immune responses against cancer cells, whereas CD8+T cells do not seem to work as sufficient effectors in tumor tissues.

scholarly journals The role of tumor infiltrating lymphocytes (TILs) and the ratios between different subsets serve as prognostic factors in hypopharyngeal squamous cell carcinoma

2020 ◽  
Author(s):  
Jie Wang ◽  
Shu Tian ◽  
Ji Sun ◽  
Jiahao Zhang ◽  
Lan Lin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cells ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Free Survival ◽  
Hypopharyngeal Squamous Cell Carcinoma ◽  
Infiltrating Lymphocytes

Abstract Background: Cancer cells induce the infiltration of various immune cells located or distributed in different sites and playing multiple roles, which have recently been proposed to predict clinical outcomes. We therefore studied the prognostic significance based on the presence of tumor infiltrating lymphocytes (TILs) and the ratios between different types of immune cells in hypopharyngeal squamous cell carcinoma (HPSCC).Methods: We retrospectively analysed 132 consecutive patients diagnosed with HPSCC in 2013-2017. Tumoral parenchyma were immunohistochemically counted manually for the number of CD8, CD4 and Foxp3. The ratios of CD8/Foxp3 and CD4/CD8 were calculated for each specimen, and analyzed with respect to patient clinicopathologic variables and prognosis. Results: HPSCC patients with high levels of TILs showed evidently correlations with well differentiated tumors (P < 0.05). Increased Foxp3+ TIL is also significantly associated with Stage and T stage (P =0.048 and P= 0.046, respectively). Kaplan-Meier analysis showed that high CD8 and FoxP3 infiltration correlated with favorable overall survival (OS, P = 0.019 and P = 0.001), disease-free survival (DFS, P = 0.045 and P = 0.028) and distant metastasis-free survival (DMFS, P = 0.034 and P = 0.009), respectively, but only FoxP3 displayed prognostic significance for DMFS in multivariate analysis (MVA). In lymphocyte ratios analysis, CD8/FoxP3 appeared to play a pivotal role, patients with high CD8/FoxP3 ratio had a superior 3-year DFS and DMFS compared with the low value of this parameter in both univariate analysis (UVA) and MVA (P = 0.015 and P=0.001). Meanwhile, high CD4/CD8 ratio had significantly better DFS and local relapse-free survival (LRFS) in UVA, and exhibited an independent prognostic factor for improved LRFS in MVA (P = 0.040).Conclusion: Although high TILs were determined to be prognostically significant in HPSCC, the ratios of these subsets may be more informative. Particularly, higher ratio of CD8/Foxp3 accurately predict prognosis for improved DFS and DMFS, and increment of CD4/CD8 ratio was an independent predictor for favorable LRFS.

PD-L1 and survival in oral cavity squamous cell carcinoma

2020 ◽  
Vol 25 (4) ◽  
pp. 287-294
Author(s):  
S. I. Kutukova ◽  
N. P. Beliak ◽  
G. A. Raskin ◽  
M. S. Mukhina ◽  
Yu. V. Ivaskova ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Squamous Cell ◽  
Immune Cells ◽  
Negative Impact ◽  
Progression Free Survival ◽  
Negative Effect ◽  
Effect Of Pd

Relevance. Prognostic value of PD-L1 expression in oral cavity squamous cell carcinoma (OCSCC) and its effect on survival is still controversial. It should be to determine the prognostic role of PD-L1 expression on tumor and immune cells of OCSCC and assess their effect on overall survival (OS) and progression-free survival (PFS).Materials and methods. A prospective study included 145 patients, first diagnosed with OCSCC. PD-L1 expression on tumor and immune cells, infiltrating tumor and its microenvironment, was assessed in all tumor samples by IHC, CPS was calculated. Cut-off values were determined by ROC analysis for identification of PD-L1 expression effect on OS and PFS.Results. Most patients with oral mucosa squamous cell carcinoma showed positive expression of PD-L1 on tumor (77.2%) and immune cells (92.4%). The median PD-L1 expression on tumor cells was 13.5% [1.0-40.0], the median PD-L1 expression on immune cells was 5.0% [1.0-11.0], and the median CPS – 18.0 [3.0-7.8]. Univariate and multivariate analyses revealed a significant negative effect of PD-L1 expression on immune cells ≤ 7% on OS (HR 0.66; 95% CI 0.45-0.93; p = 0.0498); PD-L1 expression in tumor cells ≤ 15% (HR 0.65; 95% CI 0.43-0.98; p = 0.0416) and CPS ≤ 21 (HR 0.62; 95% CI 0.44-0.92; p = 0.0183) for PFS. PD-L1 expression in tumor cells ≤ 6% (HR 0.71; 95% CI 0.47-1.08; p = 0.1096) and CPS ≤ 7 (RR 0.67; 95% CI 0.44-1.01; p = 0.0575) had a confident tendency to negative impact on OS.Conclusion. Positive PD-L1 expression in tumor and immune cells as well as CPS are effective additional factors in the prognosis of the disease course, OS and PFS in patients with OCSCC.

Expression of cyclin D1 and Ki-67 in squamous cell carcinoma of the oral cavity: clinicopathological and prognostic significance

Oral Oncology ◽  
2002 ◽  
Vol 38 (3) ◽  
pp. 301-308 ◽  
Author(s):  
Juan Carlos de Vicente ◽  
Agustı́n Herrero-Zapatero ◽  
Manuel Florentino Fresno ◽  
Juan Sebastián López-Arranz
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Cyclin D1 ◽  
Squamous Cell ◽  
Prognostic Significance ◽  
Ki 67

scholarly journals Clinicopathological Characteristics and Prognostic Factors in Axial Chondroblastomas: A Retrospective Analysis of 61 Cases and Comparison with Extra-Axial Chondroblastomas

2022 ◽  
Author(s):  
Bo-Wen Zheng ◽  
Bo-Yv Zheng ◽  
Hua-Qing Niu ◽  
Xiao-Bin Wang ◽  
Guo-Hua Lv ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Clinicopathological Characteristics ◽  
Motor Dysfunction ◽  
Surrounding Tissue ◽  
Wide Resection ◽  
Tissue Specimens

Abstract Background The clinical characteristics and prognostic factors of axial chondroblastoma (ACB) are still poorly understood. Purpose To characterize clinicopathological characteristics in a large ACB cohort and investigate their correlation with survival. We also sought to compare these results with extra-axial CB (EACB). Methods Our institution's local database was retrospectively reviewed and included a total of 132 CB patients, including 61 ACB patients and 71 EACB patients. Immunohistochemistry was used to assess the expression levels of Vimentin (Vim), S100, and cytokeratin (CK) on tumor cells in 132 tissue specimens. Results Overall, ACB and EACB had similar characteristics, except for older age and tumor size, as well as higher Vim expression, incidence of surrounding tissue invasion and postoperative sensory or motor dysfunction. Whereas wide resection and absence of invasion of surrounding tissues were consistently associated with favorable survival in the ACB and EACB cohorts in univariate analysis, most parameters showed differential prognostic significance between the 2 groups. Significant prognostic factors for local recurrence-free survival in multivariate analysis included the type of resection and chicken-wire calcification in the ACB cohort. Multivariate analysis of overall survival demonstrated that the type of resection was a significant predictor in the ACB cohort, whereas the type of resection and postoperative sensory or motor dysfunction were predictive of overall survival in the EACB group. Conclusion These data suggest that there may be distinct biological behaviors between ACB and EACB and may provide useful information to better understand the prognostic characteristics of patients with ACB and to improve outcome prediction in patients with ACB.

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.

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