Dataset Information

Patched 1 Expression Correlates with Biochemical Relapse in High-Risk Prostate Cancer Patients.

ABSTRACT: 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.

SUBMITTER: Gonnissen A

PROVIDER: S-EPMC5840486 | biostudies-other | 2018 Mar

REPOSITORIES: biostudies-other

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Publications

Patched 1 Expression Correlates with Biochemical Relapse in High-Risk Prostate Cancer Patients.

Gonnissen Annelies A Isebaert Sofie S Perneel Christiaan C McKee Chad M CM Van Utterbeeck Filip F Lerut Evelyne E Verrill Clare C Bryant Richard J RJ Joniau Steven S Muschel Ruth J RJ Haustermans Karin K

The American journal of pathology 20180112 3

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 c ...[more]

PMID: 29339090

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Project description:PURPOSE:Since the success of prostate-specific membrane antigen-positron emission tomography (PSMA-PET) imaging for patients with oligorecurrent prostate cancer (ORPC), it is increasingly used for radiotherapy as metastasis-directed therapy (MDT). Therefore, we developed a prognostic risk classification for biochemical relapse-free survival (bRFS) for patients after PSMA-PET-guided MDT after radical prostatectomy. METHODS:We analyzed 292 patients with local recurrence (LR) and/or pelvic lymph node (LN) lesions and/or up to five distant LN, bone (BM), or visceral metastases (VM) detected with [68Ga]PSMA-PET imaging. Median follow-up was 16 months (range 0-57). The primary endpoint was bRFS after MDT. Cox regression analysis for risk factors was incorporated into a recursive partitioning analysis (RPA) with classification and regression tree method. RESULTS:PSA at recurrence ??0.8 ng/mL, BM, and VM was significantly associated with biochemical relapse. RPA showed five groups with tenfold cross-validation of 0.294 (SE 0.032). After building risk classes I to IV (p?<?0.0001), mean bRFS was 36.3 months (95% CI 32.4-40.1) in class I (PSA <?0.8 ng/mL, no BM) and 25.8 months (95% CI 22.5-29.1) in class II (PSA ??0.8 ng/mL, no BM, no VM). LR and/or pelvic LNs caused relapse in classes I and II. Mean bRFS was 16.0 months (95% CI 12.4-19.6) in class III (PSA irrelevant, present BM) and 5.7 months (95% CI 2.7-8.7) in class IV (PSA ??0.8 ng/mL, no BM, present VM). CONCLUSION:We developed and internally validated a risk classification for bRFS after PSMA-PET-guided MDT. Patients with PSA <?0.8 ng/mL and local relapse only (LR and/or pelvic LNs) had the most promising bRFS. PSA ??0.8 ng/mL and local relapse only (LR and/or pelvic LNs) indicated intermediate risk for failure. Patients with BM were at higher risk regardless of the PSA. However, those patients still show satisfactory bRFS. In patients with VM, bRFS is heavily decreased. MDT in such cases should be discussed individually.

Dataset Information

Patched 1 Expression Correlates with Biochemical Relapse in High-Risk Prostate Cancer Patients.

Publications

Patched 1 Expression Correlates with Biochemical Relapse in High-Risk Prostate Cancer Patients.

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