Elsevier

Human Pathology

Volume 80, October 2018, Pages 28-39
Human Pathology

In this issue
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,☆☆

https://doi.org/10.1016/j.humpath.2018.03.025Get rights and content
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open access

Highlights

  • 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.

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.

Keywords

Programmed cell death-1 ligand-1
Tonsil
Squamous cell carcinoma
Human papillomavirus
Epithelial-to-mesenchymal transition

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Competing interests: none.

☆☆

Funding/Support: This research was supported by the Hallym University Research Fund (HURF-2017-38) and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A1B03935447) to M. J. Kwon.