Dataset Information

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.

ABSTRACT: 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).

SUBMITTER: Adamski LJ

PROVIDER: S-EPMC8471659 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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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.

Adamski Łukasz Jan ŁJ Starzyńska Anna A Adamska Paulina P Kunc Michał M Sakowicz-Burkiewicz Monika M Marvaso Giulia G Alterio Daniela D Korwat Aleksandra A Jereczek-Fossa Barbara Alicja BA Pęksa Rafał R

Biomedicines 20210901 9

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 uni ...[more]

PMID: 34572318

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Project description:ImportanceThe tongue and oral floor represent the most involved subsite by oral cancer, and there are no reported systems to classify anteroposterior tumor extension with prognostic effect. In other cancers, the anterior vs posterior tumor extension is a relevant prognostic factor.ObjectiveTo establish whether anterior vs posterior tumor extension may represent a prognostic factor in oral tongue and floor squamous cell carcinoma (OTFSCC).Design, setting, and participantsThis was a retrospective cohort study of patients who underwent surgery for OTFSCC from January 1, 2010, to December 31, 2021, at 2 tertiary-level academic institutions in Italy (University of Padua and University of Brescia). Patients eligible for the study had histologically proven primary OTFSCC; underwent surgery-based, curative treatment; and had available preoperative contrast-enhanced imaging.ExposuresFour anatomical lines were designed to assess tumor extension: (1) chin-palate line (CPL), (2) chin-basion line, (3) Stensen duct line, and (4) lingual septum line. Preoperative imaging was re-evaluated, and tumor extension was classified as either anterior or posterior according to the lines.Main outcomes and measuresOverall survival and time to recurrence (TTR) were evaluated according to tumor extension. These outcomes were reported as 5-year survival rates with 95% CIs.ResultsOf the 133 patients included, 79 (59.4%) were male, and the mean (SD) age was 62.7 (15.4) years. The 5-year TTR difference was higher for posterior vs anterior OTFSCC classified according to CPL (21.0%; 95% CI, 8.3%-33.7%), Stensen duct line (15.5%; 95% CI, 1.0%-30.0%), and lingual septum line (17.2%; 95% CI, 2.2%-32.3%). Overall survival analysis showed similar results. At the multivariable analysis on TTR, N status (adjusted hazard ratio [HR], 3.0; 95% CI, 1.2-7.1) and anteroposterior classification according to CPL (adjusted HR, 7.1; 95% CI, 0.9-54.6) were the variables associated with the highest adjusted HRs.Conclusions and relevanceIn this cohort study, OTFSCC with a posterior extension to the CPL was associated with a higher risk of recurrence and death. This analysis suggests that the poor prognosis conveyed by the posterior tumor extension is independent of other relevant prognosticators except for the burden of nodal disease. This estimate is not precise and does not allow for definitive clinically important conclusions; therefore, further prospective studies are necessary to confirm these data.

Project description:BackgroundDNA methylation profiling of heterogeneous head and neck squamous cell carcinoma (HNSCC) cohorts has been reported to predict patient outcome. We investigated if a prognostic DNA methylation profile could be found in tumour tissue from a single uniform subsite, the oral tongue. The methylation status of 109 comprehensively annotated oral tongue squamous cell carcinoma (OTSCC) formalin-fixed paraffin-embedded (FFPE) samples from a single institution were examined with the Illumina HumanMethylation450K (HM450K) array. Data pre-processing, quality control and analysis were performed using R packages. Probes mapping to SNPs, sex chromosomes and unreliable probes were accounted for prior to downstream analyses. The relationship between methylation and patient survival was examined using both agnostic approaches and feature selection. The cohort was enlarged by incorporation of 331 The Cancer Genome Atlas (TCGA) HNSCC samples, which included 91 TCGA OTSCC samples with HM450K and survival data available.ResultsGiven the use of FFPE-derived DNA, we defined different cohorts for separate analyses. Overall, similar results were found between cohorts. With an unsupervised approach, no distinct hypermethylated group of samples was identified and nor was a prognostic methylation profile identified. The use of multiple downstream feature selection approaches, including a linear models for microarray data (LIMMA), centroid feature selection (CFS), and recursive feature elimination (RFE) support vector machines, similarly failed to identify a significant methylation signature informative for patient prognosis or any clinicopathological data available. Furthermore, we were unable to confirm the prognostic methylation profiles or specific prognostic loci reported within the literature for HNSCC.ConclusionsWith genome-scale assessment of DNA methylation using HM450K in one of the largest OTSCC cohorts to date, we were unable to identify a hypermethylated group of tumours or a prognostic methylation signature. This suggests that either DNA methylation in isolation is not likely to be of prognostic value or larger cohorts are required to identify such a biomarker for OTSCC.

Dataset Information

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.

Publications

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.

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