TY - JOUR
T1 - Patched 1 Expression Correlates with Biochemical Relapse in High-Risk Prostate Cancer Patients
AU - Gonnissen, Annelies
AU - Isebaert, Sofie
AU - Perneel, Christiaan
AU - McKee, Chad M.
AU - Van Utterbeeck, Filip
AU - Lerut, Evelyne
AU - Verrill, Clare
AU - Bryant, Richard J.
AU - Joniau, Steven
AU - Muschel, Ruth J.
AU - Haustermans, Karin
N1 - Publisher Copyright:
© 2018 American Society for Investigative Pathology
PY - 2018/3
Y1 - 2018/3
N2 - There is an unmet clinical need for adequate biomarkers to aid risk stratification and management of prostate cancer (PCa) patients. Even within the high-risk PCa category, not all patients will invariably have a poor prognosis, and improved stratification of this heterogeneous group is needed. In this context, components of the hedgehog (Hh) pathway may have promise as biomarkers, because the available evidence suggests increased Hh pathway activity may confer a poorer outcome in advanced and castrate-resistant PCa. In this study, potential associations between Hh pathway protein expression and clinicopathological factors, including time to biochemical recurrence (BCR), were investigated using a tissue microarray constructed from benign and malignant prostate samples from 75 predominantly high-risk PCa patients who underwent radical prostatectomy. Hh signaling activity was found to differ between benign and malignant prostate tissue, with a greater amount of active Hh signaling present in malignant than benign prostate epithelium. High expression of Patched 1 in malignant prostate epithelium was found to be an independent predictor of BCR in high-risk PCa patients. Glioma-associated oncogene 1 may potentially represent a clinically useful biomarker of an aggressive tumor phenotype. Evaluation of Hh signaling activity in PCa patients may be useful for risk stratification, and epithelial Patched 1 expression, in particular, may be a prognostic marker for BCR in high-risk PCa patients.
AB - There is an unmet clinical need for adequate biomarkers to aid risk stratification and management of prostate cancer (PCa) patients. Even within the high-risk PCa category, not all patients will invariably have a poor prognosis, and improved stratification of this heterogeneous group is needed. In this context, components of the hedgehog (Hh) pathway may have promise as biomarkers, because the available evidence suggests increased Hh pathway activity may confer a poorer outcome in advanced and castrate-resistant PCa. In this study, potential associations between Hh pathway protein expression and clinicopathological factors, including time to biochemical recurrence (BCR), were investigated using a tissue microarray constructed from benign and malignant prostate samples from 75 predominantly high-risk PCa patients who underwent radical prostatectomy. Hh signaling activity was found to differ between benign and malignant prostate tissue, with a greater amount of active Hh signaling present in malignant than benign prostate epithelium. High expression of Patched 1 in malignant prostate epithelium was found to be an independent predictor of BCR in high-risk PCa patients. Glioma-associated oncogene 1 may potentially represent a clinically useful biomarker of an aggressive tumor phenotype. Evaluation of Hh signaling activity in PCa patients may be useful for risk stratification, and epithelial Patched 1 expression, in particular, may be a prognostic marker for BCR in high-risk PCa patients.
UR - http://www.scopus.com/inward/record.url?scp=85042311635&partnerID=8YFLogxK
U2 - 10.1016/j.ajpath.2017.11.019
DO - 10.1016/j.ajpath.2017.11.019
M3 - Article
C2 - 29339090
AN - SCOPUS:85042311635
SN - 0002-9440
VL - 188
SP - 795
EP - 804
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -