Benign prostatic hyperplasia to HPIN to carcinoma - the impact of mast cells and VEGF - Research Open Access

Sep 22, 2026

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Transformation from benign prostatic hyperplasia (BPH) to prostate cancer (PCa) remains debated, yet evidence supports an inflammatory background. Multifocal high-grade prostatic intraepithelial neoplasia (HPIN), intraductal carcinoma (IDC-P), atypical intraductal proliferation (AIP), atypical adenomatous hyperplasia (AAH)/adenosis, and proliferative inflammatory atrophy (PIA) are discussed as precursor lesions. This study examines vascular endothelial growth factor (VEGF) and mast cells (MCs) during BPH-to-PCa progression, including MC associations with Gleason grade group and other prognostic variables.

LanguageEnglish

CategoryHealthcare

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Abstract

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Methods

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Sivrikoz et al. Diagnostic Pathology (2026) 21:10 [https://doi.org/10.1186/s13000-026-01749-z](https://doi.org/10.1186/s13000-026-01749-z) Diagnostic Pathology RESEARCH Open Access Benign prostatic hyperplasia to HPINto carcinoma; the impact of mast cells and VEGF Oya Nermin Sivrikoz1*, Aşkın Eroğlu2, Bilgin Öztürk2, İncila Öztop1 and Salahattin M. Sanal3 Abstract Background The process of transformation from Benign Prostatic Hyperplasia (BPH) to Prostate Cancer (PCa) is highly debatable; however, there is convincing information that it takes place in the background of inflammation. Multifocal high-grade prostatic intraepithelial neoplasia (HPIN), intraductal carcinoma (IDC-P), atypical intraductal proliferation (AIP), atypical adenomatous hyperplasia (AAH)/ adenosis, and proliferative inflammatory atrophy (PIA) are considered as precursor lesions during such transformation by Working Group 1 at the ISUP Cancer Precursors Meeting in September 2024. We specifically emphasize the need for further investigation of the inflammatory process, where stromal epithelial activity, angiogenesis, and mast cells are involved. In this study, we investigated the role of vascular endothelial growth factor (VEGF), and MCs during its progression from BPH to PCa. Additionally, we investigated the relationship between MCs and Gleason Grade Group (GG), as well as other prognostic variables. Methods Retrospectively, 100 PCa patients whose pathology included areas of BPH and multifocal HPIN close to cancerous tissue. All the specimens were stained with CD117 as an MC marker and VEGF to evaluate for angiogenesis. Results While there was overall intense MC infiltration in all areas of BPH in general, it was relatively less intense in areas of carcinomatous tissue. Nevertheless, MC infiltration intensified with higher GG. Similarly, with increasing MC infiltration in cancerous and HPIN tissues, VEGF staining also intensified, specifically in glandular areas. In HPIN areas, the relationship between MCs and VEGF was intermediate between BPH and cancerous areas, representing a progression. Conclusion Stromal changes, stromal-epithelial interactions, and coexisting inflammatory changes are important elements in the development of BPH and PCa. We specifically investigated the intratumoral MC population and glandular VEGF staining intensity with increasing GG; thus, assessing the role of MCs and VEGF in tumor progression towards cancer development. MCs and VEGF staining characteristics in HPIN areas emphasize the efficient role these elements play in the transition of tissues from BPH to HPIN and eventually to PCa. *Correspondence: Oya Nermin Sivrikoz [onsoral@yahoo.com](onsoral@yahoo.com) 1Baskent University Department of Pathology, Izmir, Turkey 2Baskent University Department of Urology, Izmir, Turkey 3ONKOMER Oncology Center, Izmir, Turkey © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/licenses/by-nc-nd/4.0/](vecommons.org/licenses/by-nc-nd/4.0/.)[.](vecommon

FAQs

What question does the study address about BPH progression?

It investigates how the progression from benign prostatic hyperplasia (BPH) toward prostate cancer is linked to inflammatory mechanisms, focusing on mast cells and angiogenesis-related VEGF.

How were mast cells and VEGF evaluated in the specimens?

The study retrospectively stained pathology specimens for CD117 as a mast cell marker and for VEGF to assess angiogenesis, using areas containing BPH and multifocal HPIN near cancerous tissue.

What relationship did the study find between mast cells, VEGF, and Gleason grade group?

MC infiltration intensified with higher Gleason grade group, and VEGF staining also increased with greater MC infiltration, particularly in glandular areas; the MC-VEGF relationship in HPIN was intermediate between BPH and cancerous tissues.

Sep 22, 2026

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