p53 Expression, Programmed Death Ligand 1, and Risk Factors in Urinary Tract Small Cell Carcinoma

Borivoj Golijanin; Boris Gershman; Andre De Souza; Ohad Kott; Benedito A Carneiro; Anthony Mega; Dragan J Golijanin; Ali Amin

doi:10.3389/fonc.2021.651754

p53 Expression, Programmed Death Ligand 1, and Risk Factors in Urinary Tract Small Cell Carcinoma

Front Oncol. 2021 Apr 22:11:651754. doi: 10.3389/fonc.2021.651754. eCollection 2021.

Authors

Borivoj Golijanin^{1

2}, Boris Gershman³, Andre De Souza⁴, Ohad Kott², Benedito A Carneiro⁴, Anthony Mega⁴, Dragan J Golijanin², Ali Amin¹

Affiliations

¹ Department of Pathology and Laboratory Medicine, The Miriam Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, United States.
² Urology Department, Minimally Invasive Urology Institute, The Miriam Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, United States.
³ Division of Urologic Surgery, Beth Israel Deaconess Medical Center, Boston, MA, United States.
⁴ Oncology Department, Lifespan Cancer Institute, The Miriam Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, United States.

Abstract

Introduction: Small cell carcinoma of the urinary tract (SCCUT) is a rare finding with poor clinical course. This study sheds light on the molecular subtype and identifies risk factors in patients diagnosed with SCCUT. Methods: Immunohistochemical expression of immunotherapy target programmed death ligand 1 (PD-L1) and luminal (GATA3), basal (p63), and p53 markers are assessed in patients diagnosed with SCCUT. Univariate analysis identified risk factors. Overall survival (OS) is computed using the Kaplan-Meier method. Results: Tissue was available for 70.2% (33/47). All showed a high PD-L1 expression phenotype. p53 is seen in 93.9% (31/33), mostly as overexpression, GATA3 in 45.5% (15/33), and p63 in 57.6% (19/33). For the entire cohort (n = 47), 1-year survival was 59.6%, and the median OS was 17 months. Univariate analysis shows that chemotherapy [hazard ratio (HR) = 0.29, 95% confidence interval (CI) = 0.14-0.61, p = 0.001], radical surgery (HR = 0.37, 95% CI = 0.18-0.76, p = 0.007), and diagnosis of non-pure SCCUT (HR = 0.44, 95% CI = 0.22-0.86, p = 0.02) are favorable prognostic features. Metastasis had negative associations with survival (HR = 2.1, 95% CI = 1.1-4.2, p = 0.03). Conclusions: In this series, pure and mixed SCCUT are characterized by p53 overexpression and a high PD-L1 phenotype. Histology of non-pure SCCUT is a positive prognosticator, and radical cystectomy or chemotherapy can improve OS. These findings demonstrate that SCCUT may be eligible for PD-L1 immunotherapy.

Keywords: PD-L1; bladder; p53; risk factors; small cell carcinoma; survival.