Research Papers: Pathology:

Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells

Joao Paulo Oliveira-Costa _, Alex Fiorini de Carvalho, Giorgia Gobbi da Silveira, Peter Amaya, Yongqi Wu, Kyoung-Joo Jenny Park, Mabel Pinilla Gigliola, Maryam Lustberg, Marcilei Eliza Cavicchioli Buim, Elisa Napolitano Ferreira, Luiz Paulo Kowalski, Jeffrey J. Chalmers, Fernando Augusto Soares, Dirce Maria Carraro and Alfredo Ribeiro-Silva

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Oncotarget. 2015; 6:20902-20920. https://doi.org/10.18632/oncotarget.3939

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Joao Paulo Oliveira-Costa1, Alex Fiorini de Carvalho2, Giorgia Gobbi da Silveira1, Peter Amaya3, Yongqi Wu3, Kyoung-Joo Jenny Park3, Mabel Pinilla Gigliola2, Maryam Lustberg4, Marcilei Eliza Cavicchioli Buim5, Elisa Napolitano Ferreira2, Luiz Paulo Kowalski6, Jeffrey J. Chalmers3, Fernando Augusto Soares5, Dirce Maria Carraro2, Alfredo Ribeiro-Silva1

1Department of Pathology, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil

2Laboratory of Genomics and Molecular Biology, CIPE, A.C. Camargo Cancer Center, Sao Paulo, Brazil

3William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA

4Stefanie Spielman Comprehensive Breast Center, Wexner Medical Center, The Ohio State University, Columbus, OH, USA

5Department of Anatomic Pathology, A.C. Camargo Cancer Center, Sao Paulo, Brazil

6Department of Head and Neck Surgery and Otorhinolaryngology, A.C. Camargo Cancer Center, Sao Paulo, Brazil

Correspondence to:

Joao Paulo Oliveira-Costa, e-mail: [email protected]

Keywords: PD-L1, oral squamous cell carcinoma, gene expression, circulating tumor cells, survival

Received: February 23, 2015     Accepted: May 05, 2015     Published: May 15, 2015


Oral squamous cell carcinoma (OSCC) is the most common tumor of the oral cavity and has been associated with poor prognosis. Scarce prognostic markers are available for guiding treatment and/or sub-classifying patients. This study aims to identify biomarkers by searching for genes whose expression is increased or decreased during tumor progression (through T1 to T4 stages). Thirty-six samples from all tumor size stages (from T1 to T4) were analyzed using cDNA microarrays. Selected targets were analyzed by immunohistochemistry and in circulating tumor cells by immunofluorescence and Nanostring. Correlation was shown between PD-L1 and tumor size and lymph node metastasis, HOXB9 and tumor size, BLNK and perineural invasion, and between ZNF813 and perineural invasion. PD-L1 positivity was an independent prognostic factor in this cohort (p = 0.044, HH = 0.426). In CTCs from patients with locally advanced OSCC, we found a strong cytoplasmatic expression of PD-L1. PD-L1 is a ligand of PD-1 and is believed to limit T cell activity in inflammatory responses and limit autoimmune diseases. We demonstrated an important role for PD-L1 in primary tumors according to tumor size, and in disease specific survival. Therefore, we could further determine individuals with PD-L1+ CTCs, and possibly follow treatment using CTCs.

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