Clinical implication of programmed cell death-1 ligand-1 expression in tonsillar squamous cell carcinoma in association with intratumoral heterogeneity, human papillomavirus, and epithelial-to-mesenchymal transition

Programmed cell death-1 ligand-1 (PD-L1), essential for immune evasion, is a potential candidate for pathogenesis and therapeutic target of human papillomavirus (HPV)–positive tonsillar squamous cell carcinomas (TSCCs). MET/hepatocyte growth factor signaling and transcription factors involved in epi...

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Published in:Human pathology 2018-10, Vol.80, p.28-39
Main Authors: Kwon, Mi Jung, Rho, Young-Soo, Nam, Eun Sook, Cho, Seong Jin, Park, Hye-Rim, Min, Soo Kee, Seo, Jinwon, Choe, Ji-Young, Kim, Eun Soo, Park, Bumjung, Hong, Mineui, Min, Kyueng-Whan
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Alcohol
Antigens
Apoptosis
B7-H1 Antigen - metabolism
Biomarkers, Tumor - analysis
Cancer
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - pathology
Cell death
Cell Death - physiology
Epithelial-Mesenchymal Transition - genetics
Epithelial-to-mesenchymal transition
Female
Human papillomavirus
Humans
Kinases
Ligands
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Male
Medical prognosis
Medical records
Middle Aged
Multivariate analysis
Papillomaviridae - pathogenicity
Patients
Programmed cell death-1 ligand-1
Proteins
Radiation therapy
Squamous cell carcinoma
Studies
Tonsil
Tonsillar Neoplasms - genetics
Tonsillar Neoplasms - virology
Transcription factors
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Summary:Programmed cell death-1 ligand-1 (PD-L1), essential for immune evasion, is a potential candidate for pathogenesis and therapeutic target of human papillomavirus (HPV)–positive tonsillar squamous cell carcinomas (TSCCs). MET/hepatocyte growth factor signaling and transcription factors involved in epithelial-to-mesenchymal transition (EMT) upregulate PD-L1, which can contribute to clinical outcome. Intratumoral heterogeneity of PD-L1 expression is of clinical importance in selection bias due to false-negative patient enrollment. However, the clinicopathological features, prognostic value, and coexpressed molecules of PD-L1 remain unclear in TSCCs. PD-L1 expression was evaluated via immunohistochemistry using a specific monoclonal antibody (SP142) between whole-tissue and tissue microarray (TMA) sections of 79 tumors (5% cutoff value with weak staining). Expressions of EMT markers (TWIST1, Snail, and SNIP1) and MET/hepatocyte growth factor were also analyzed. Staining of the TMA sections showed 78.5% concordance rate to the whole section. PD-L1 positivity and its intratumoral heterogeneity were 29.1% and 15.2% of TSCCs by whole section, respectively. PD-L1 positivity was prevalent in females, HPV-positive tumors without base of tongue invasion, and SNIP1-overexpressed tumors. SNIP1 overexpression, unmethylated TWIST1, smoking, and poorly differentiated tumors were predictive for PD-L1 overexpression. PD-L1 positivity was a favorable independent prognostic factor. Subgroup analyses according to the coexpression of PD-L1 with HPV, SNIP1, or unmethylated TWIST1 indicated the best clinical outcome than any other subgroups. In conclusion, intratumoral heterogeneity of PD-L1 expression was frequent, warranting a caution in punching TMA cores. A combined analysis of PD-L1 with EMT and HPV may define a characteristic subset of patients and prognostic group. •PD-L1 expression is heterogeneous in tonsil cancers, causing false-negative results in tissue microarray.•Human papillomavirus and epithelial-to-mesenchymal transition are PD-L1 upregulators.•PD-L1 expression is a favorable prognostic factor in tonsil cancers.
ISSN:0046-8177
1532-8392
DOI:10.1016/j.humpath.2018.03.025