Endothelial p16 expression identifies a subgroup of clear cell renal cell carcinoma with favorable prognosis
6 affiliations
- 1Institute of Pathology, University Hospital Bonn, Bonn, Germany
- 2Department of Urology, St. Josef-Hospital, Troisdorf, Germany
- 3Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany
- 4Center of Integrated Oncology – CIO ABCD, University Hospital Bonn, Bonn, Germany
- 5Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany
- 6Department of Urology, Johanniter-Krankenhaus Bonn, Bonn, Germany
Abstract
Background: Clear cell renal cell carcinoma (ccRCC) is characterized by extensive angiogenesis and marked architectural heterogeneity. While vascular density has been investigated as a prognostic parameter in ccRCC, little is known about the biological characteristics of intratumoral endothelial cells.
Methods: In this study, we analyzed the p16 expression in a tissue microarray cohort comprising 347 ccRCC cases with clinicopathological and survival data and related the vascular p16 expression to previously described tumor architecture subtypes.
Results: Tumor architecture could be assessed in 315 cases and was classified into nine predominant growth patterns. Tumors with thick trabecular/insular or solid sheet architecture were grouped as high-risk patterns and were associated with higher tumor grade and shorter overall survival (p < 0.001). Tumor cell p16 expression was infrequent and showed no association with clinicopathological parameters or survival. In contrast, endothelial p16 expression was commonly observed in intratumoral blood vessels, with a median of 35% positive vessels per case. Higher endothelial p16 expression, both in extent and intensity, was significantly associated with lower tumor grade, lower pT stage, favorable architectural patterns, and prolonged overall survival. Furthermore, the prognostic impact of architectural growth patterns was most pronounced in tumors with low endothelial p16 expression, whereas tumors with high endothelial p16 expression showed comparable survival independent of architectural subtype.
Conclusion: Endothelial p16 expression is common in ccRCC and is associated with favorable clinicopathological characteristics and prolonged survival. These findings suggest that endothelial p16 expression may complement architectural tumor stratification in ccRCC, identifying cases with good prognosis.
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BibTeX
@article{stoffel2026endothelial,
title = {{Endothelial p16 expression identifies a subgroup of clear cell renal cell carcinoma with favorable prognosis}},
author = {Michael Stoffel and Katharina Baschun and Melina Kehl and Jörg Ellinger and Niklas Klümper and Sebastian Kadzik and Franziska I. Winterhagen and Manuel Ritter and Michael Hölzel and Glen Kristiansen and Marieta I. Toma},
journal = {BMC Cancer},
year = {2026},
month = oct,
doi = {10.1186/s12885-026-17178-6},
url = {https://doi.org/10.1186/s12885-026-17178-6},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Endothelial p16 expression identifies a subgroup of clear cell renal cell carcinoma with favorable prognosis
AU - Michael Stoffel
AU - Katharina Baschun
AU - Melina Kehl
AU - Jörg Ellinger
AU - Niklas Klümper
AU - Sebastian Kadzik
AU - Franziska I. Winterhagen
AU - Manuel Ritter
AU - Michael Hölzel
AU - Glen Kristiansen
AU - Marieta I. Toma
PY - 2026
DA - 2026/10/26
JO - BMC Cancer
DO - 10.1186/s12885-026-17178-6
UR - https://doi.org/10.1186/s12885-026-17178-6
AB - Background: Clear cell renal cell carcinoma (ccRCC) is characterized by extensive angiogenesis and marked architectural heterogeneity. While vascular density has been investigated as a prognostic parameter in ccRCC, little is known about the biological characteristics of intratumoral endothelial cells. Methods: In this study, we analyzed the p16 expression in a tissue microarray cohort comprising 347 ccRCC cases with clinicopathological and survival data and related the vascular p16 expression to previously described tumor architecture subtypes. Results: Tumor architecture could be assessed in 315 cases and was classified into nine predominant growth patterns. Tumors with thick trabecular/insular or solid sheet architecture were grouped as high-risk patterns and were associated with higher tumor grade and shorter overall survival (p < 0.001). Tumor cell p16 expression was infrequent and showed no association with clinicopathological parameters or survival. In contrast, endothelial p16 expression was commonly observed in intratumoral blood vessels, with a median of 35% positive vessels per case. Higher endothelial p16 expression, both in extent and intensity, was significantly associated with lower tumor grade, lower pT stage, favorable architectural patterns, and prolonged overall survival. Furthermore, the prognostic impact of architectural growth patterns was most pronounced in tumors with low endothelial p16 expression, whereas tumors with high endothelial p16 expression showed comparable survival independent of architectural subtype. Conclusion: Endothelial p16 expression is common in ccRCC and is associated with favorable clinicopathological characteristics and prolonged survival. These findings suggest that endothelial p16 expression may complement architectural tumor stratification in ccRCC, identifying cases with good prognosis.
SN - 1471-2407
ER -