Abstract
In patients treated for prostate cancer (PCa) with radical prostatectomy (RP), determining the risk of extraprostatic extension (EPE) and nodal involvement (NI) remains crucial for planning nerve-sparing and extended lymphadenectomy. The study aimed to determine proteins that could serve as immunohistochemical markers of locally advanced PCa. To select candidate proteins associated with adverse pathologic features (APF) reverse-phase protein array data of 498 patients was retrieved from The Cancer Genome Atlas. The analysis yielded 6 proteins which were then validated as predictors of APF utilizing immunohistochemistry in a randomly selected retrospective cohort of 53 patients. For univariate and multivariate analysis, logistic regression was used. Positive expression of TfR1 (OR 13.74; p = 0.015), reduced expression of CD49b (OR 10.15; p = 0.013), and PSA (OR 1.29; p = 0.013) constituted independent predictors of EPE, whereas reduced expression of e-cadherin (OR 10.22; p = 0.005), reduced expression of CD49b (OR 24.44; p = 0.017), and PSA (OR 1.18; p = 0.002) were independently associated with NI. Both models achieved high discrimination (AUROC 0.879 and 0.888, respectively). Immunohistochemistry constitutes a straightforward tool that might be easily utilized before RP. Expression of TfR1 and CD49b is associated with EPE, whereas expression of e-cadherin and CD49b is associated with NI. Since following immunohistochemical markers predicts respective APFs independently from PSA, in the future they might supplement existing preoperative nomograms or be implemented in novel tools.
Highlights
IntroductionAlong with advances in surgical technique, salvage therapies, and in the perspective of emerging neoadjuvant options, radical prostatectomy (RP) is being constantly confirmed as the fundament of multimodal treatment for locally advanced prostate cancer [1]
Screening selection was based on outcomes of univariate logistic regression and yielded expression of 6 proteins–integrin alpha-2 (CD49b), e-cadherin, heregulin, neurofibromin 2 (NF2), phosphatase and tensin homolog (PTEN), and transferrin receptor 1 (TfR1), predicting nodal involvement (NI) both in development and validation subsets
We presented immunohistochemical validation of the preselected protein markers of adverse pathologic features of prostate cancer
Summary
Along with advances in surgical technique, salvage therapies, and in the perspective of emerging neoadjuvant options, radical prostatectomy (RP) is being constantly confirmed as the fundament of multimodal treatment for locally advanced prostate cancer [1]. In patients treated with radical prostatectomy, preoperative prediction of pN1 and pT3 disease remains crucial for lymphadenectomy [2,3] and nerve-sparing [4] issues, respectively. The pathophysiology of the local and nodal spread of prostate cancer (PCa) remains poorly understood. Tors of extraprostatic extension (EPE) and nodal involvement (NI) to date. None of these has been considered a clinically valid marker, which can aid decision making. The study aimed to determine protein markers of NI that could potentially be used as immunohistochemical markers of locally advanced prostate cancer
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