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PD-1, PD-L1 and cAMP immunohistochemical expressions are associated with worse oncological outcome in patients with bladder cancer.


ABSTRACT:

Purpose

In this study, we aimed to identify prognostic factors of cancer mortality in patients who received radical cystectomy and to identify genomic alterations in a sub-cohort of patients with locally advanced (pT3-4) and/or positive lymph nodes bladder cancer (BC).

Methods

We collected 101 BC samples from 2010 to 2018 who previously received radical cystectomy. Immunohistochemical slides were evaluated for PPAR, cAMP, IMP3, Ki67, CDK4, POU5F1, Cyclin E and MDM2, p65, CD3, CD4, CD8, CD20, CD68, CD163, FOXP3, PD-1 and PD-L1 expression. We calculated a prognostic score (PS) based on the positivity to PD-1, PD-L1 and of cAMP (final score ranging from 0 to 3). DNA of each sample have been used for sequencing by NGS in a sub-cohort of 6 patients with locally advanced (pT3-4) and/or positive lymph nodes BC.

Results

PD-1 + (HR [hazard ratio] 2.59; p = 0.04), PD-L1+ (HR = 6.46; p < 0.01) and cAMP+ (HR 3.04; p = 0.02) were independent predictors of cancer-specific mortality (CSM). Increase of PS (score = 0 as reference) was associated with CSM, 0.81 (p = 0.80), 4.72 (p = 0.01) and 10.51 (p < 0.0) for PS 1, 2 and 3, respectively. ERBB2 was the gene most frequently mutated.

Conclusion

BC exhibited heterogenous protein expression and variable genomic features. Identification of expression of PD-1, PD-L1 and cAMP could help in predicting oncological outcomes.

SUBMITTER: Russo GI 

PROVIDER: S-EPMC10314864 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

PD-1, PD-L1 and cAMP immunohistochemical expressions are associated with worse oncological outcome in patients with bladder cancer.

Russo Giorgio Ivan GI   Musso Nicolò N   Lo Giudice Arturo A   Asmundo Maria Giovanna MG   Di Mauro Marina M   Bonacci Paolo G PG   Massimino Mariacristina M   Bivona Dalida D   Stefani Stefania S   Pricoco Elisabetta E   Ferro Matteo M   Camarda Massimo M   Cimino Sebastiano S   Morgia Giuseppe G   Caltabiano Rosario R   Broggi Giuseppe G  

Journal of cancer research and clinical oncology 20220816 7


<h4>Purpose</h4>In this study, we aimed to identify prognostic factors of cancer mortality in patients who received radical cystectomy and to identify genomic alterations in a sub-cohort of patients with locally advanced (pT3-4) and/or positive lymph nodes bladder cancer (BC).<h4>Methods</h4>We collected 101 BC samples from 2010 to 2018 who previously received radical cystectomy. Immunohistochemical slides were evaluated for PPAR, cAMP, IMP3, Ki67, CDK4, POU5F1, Cyclin E and MDM2, p65, CD3, CD4,  ...[more]

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