Journal Article

Tissue microarray analysis indicates hedgehog signaling as a potential prognostic factor in intermediate-risk prostate cancer

Perneel, Christiaan, Bryant, Richard J., Haustermans, Karin, Muschel, Ruth J., McKee, Chad M., Van Utterbeeck, Filip, Lerut, Evelyne, Isebaert, Sofie, Verrill, Clare, Gonnissen, Annelies

2017

Overview

Background Prostate cancer (PCa) is a heterogeneous disease with a variable natural history, genetics, and treatment outcome. The Hedgehog (Hh) signaling pathway is increasingly recognized as being potentially important for the development and progression of PCa. In this retrospective study, we compared the activation status of the Hh signaling pathway between benign and tumor tissue, and evaluated the clinical significance of Hh signaling in PCa. Methods In this tissue microarray (TMA) study, the protein expression of several Hh signaling components and Hh target proteins, along with microvessel density, were compared between benign ( n  = 64) and malignant ( n  = 170) prostate tissue, and correlated with PCa clinicopathological characteristics and biochemical recurrence (BCR). Results The Hh signaling pathway appeared to be more active in PCa than in benign prostate tissue, as demonstrated by lower expression of the negative regulators PTCH1 and GLI3 in the tumor tissue compared to benign. In addition, high epithelial GLI2 expression correlated with higher pathological Gleason score. Overall, higher epithelial GLI3 expression in the tumor was shown to be an independent marker of a favorable prognosis. Conclusion Hh signaling activation might reflect aggressive tumoral behavior, since high epithelial GLI2 expression positively correlates with a higher pathological Gleason score. Moreover, higher epithelial GLI3 expression is an independent marker of a more favorable prognosis.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Benign / Biochemical recurrence / Biomedical and Life Sciences / Biomedicine / Cancer Research / Comparative analysis / Disease Progression / DNA microarrays / Follow-Up Studies / Health aspects / Health Promotion and Disease Prevention / Hedgehog pathway / Hedgehog protein / Hedgehog Proteins - metabolism / Histopathology / Humans / Immunoglobulins / Immunohistochemistry / Laboratories / Male / Medical prognosis / Medical research / Medicine/Public Health / Middle Aged / Models, Biological / Neoplasm Grading / Neoplasm Staging / Oncology / Patients / Prognosis / Prostate cancer / Prostatic Neoplasms - metabolism / Prostatic Neoplasms - mortality / Prostatic Neoplasms - pathology / Protein arrays / Protein expression / Proteins / Recurrence / Research Article / Risk factors / Signal Transduction / Studies / Surgical Oncology / Survival Analysis / Tissue Array Analysis / Tissue microarray / Translational oncology