Correlation between messenger RNA expression and protein expression of immune checkpoint-associated molecules in bladder urothelial carcinoma: A retrospective study

Immunotherapy for bladder cancer seems to have promising results. Here, we evaluated the association between messenger RNA (mRNA) and protein levels and possible prognostic value of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) immune checkpoint pathways during bladder carcinogenesis.

Tumor samples were obtained from 155 patients (84 with muscle-invasive bladder cancer [MIBC], and 71 non-muscle-invasive bladder cancer [NMIBC]) and normal bladder tissue from 15 patients. We evaluated the mRNA expression of 3 genes in the PD-1 pathway (PD-1, PD-L1, and PD-L2) and 4 in the CTLA4 pathway (CTLA4, CD28, CD80, and CD86) in normal and tumoral human bladder samples by quantitative real-time reverse transcription polymerase chain reaction, with immunohistochemistry used to evaluate the protein expression of PD-1 and PD-L1 in tumor and immune cells. Results of molecular analyses were compared with survival analyses.

As compared with normal bladder tissue, MIBC tissue showed PD-1, PD-L1, CTLA4, and CD80 overexpression (59.5%, 60.7%, 84.5%, and 92.9%, respectively), whereas overexpression was lower in NMIBC tissue (22.5%, 4.2%, 35.2%, and 46.5%, respectively). The results of reverse transcription polymerase chain reaction analysis were confirmed by immunohistochemistry, with a high correlation between mRNA and protein expression. On multivariate analyses, overexpression of the studied genes was not associated with prognosis in relapse or progression of NMIBC or in recurrence-free and overall survival of MIBC.

The CTLA4 pathway appears to be deregulated along with the PD-1/PD-L1 pathway in bladder carcinogenesis, with good correlation between mRNA and protein expression endorsing the useful role of immune checkpoints, especially for a large subgroup of MIBC.

Urologic oncology. 2017 Mar 10 [Epub ahead of print]

Constance Le Goux, Diane Damotte, Sophie Vacher, Mathilde Sibony, Nicolas Barry Delongchamps, Anne Schnitzler, Benoit Terris, Marc Zerbib, Ivan Bieche, Géraldine Pignot

Unité de Pharmacogénomique, Service de génétique, Institut Curie, Paris, France., Service d׳Anatomopathologie, Hôpital Cochin, Université Paris Descartes, Paris, France; Cancer et Immunité anti tumorale, INSERM U1138, Centre de Recherche des Cordeliers, Paris, France., Service d׳Anatomopathologie, Hôpital Cochin, Université Paris Descartes, Paris, France., Service d׳Urologie, Hôpital Cochin, Université Paris Descartes, Paris, France., Unité de Pharmacogénomique, Service de génétique, Institut Curie, Paris, France; Université Paris Descartes, Paris, France., Service d׳Urologie, Institut Paoli-Calmettes, Marseille, France. Electronic address: .

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