Abstract
Simple SummaryThe expression of the androgen receptor (AR) and its splice variant AR-V7 is crucial for prostate cancer (PCa) biology. An immunohistochemical staining was performed on a tissue microarray with specimens from 410 PCa patients. AR staining, neither in the nucleus nor in the cytoplasm was associated with prognosis. AR-V7 staining of the general cytoplasm was associated with a shorter relapse free survival (RFS), whereas AR-V7 staining of cytoplasmic granules was associated with a longer RFS. Further subgroup stratification for AR-V7 granular staining revealed it as an independent prognostic factor in younger patients (age ≤ 65), patients with negative CK20 staining and patients with perineural invasion. Altogether, AR-V7 protein detected in granular cytoplasmic structures is an independent prognostic factor for RFS in PCa patients.Prostate cancer (PCa) is the second most common cancer, causing morbidity and mortality among men world-wide. The expression of the androgen receptor (AR) and its splice variants is a crucial factor of prostate cancer biology that has not been comprehensively studied in PCa tumors. The aim of this study was to characterize the protein expression of the AR and its splice variant, AR-V7, and their subcellular distributions in PCa by immunohistochemistry and to correlate the results to the clinicopathological data and prognosis. Immunohistochemical staining for AR and AR-V7 was performed on a tissue microarray (TMA) with specimens from 410 PCa patients using an immunoreactive score (IRS) or only the percentage of AR-V7 staining in cytoplasmic granules. Nuclear or cytoplasmic AR staining was not associated with prognosis. AR-V7 staining was only occasionally observed in the nucleus. However, AR-V7 staining in the cytoplasm or in cytoplasmic granules was associated with relapse-free survival (RFS). AR-V7 staining of the cytoplasm was associated with a shorter RFS, whereas AR-V7 staining of cytoplasmic granules was associated with a longer RFS. In a multivariate Cox’s regression analysis, only negative (<5%) AR-V7 staining of cytoplasmic granules remained an independent prognostic factor for RFS (HR = 5.3; p = 0.006). In a further subgroup analysis by multivariate Cox’s regression analysis, AR-V7 was an independent prognostic factor in the following groups: age ≤ 65 (HR = 9.7; p = 0.029), negative CK20 staining (HR = 7.0; p = 0.008), and positive perineural invasion (HR = 3.7; p = 0.034). Altogether, AR-V7 protein in granular cytoplasmic structures is an independent prognostic factor for RFS in PCa patients.
Highlights
Prostate cancer (PCa) represents the second most common cancer and the fifth most common cause of cancer-associated death in men globally [1]
androgen receptor (AR) staining was detected in the nucleus and cytoplasm, Cancers
AR staining was detected in the nucleus and in the cytoplasm, whereas AR-V7 staining was seen in the cytoplasm as general staining and/or localized in cytoplasmic granule-like structures
Summary
Prostate cancer (PCa) represents the second most common cancer and the fifth most common cause of cancer-associated death in men globally [1]. PCa is a group of histologically and molecularly heterogeneous diseases with variable clinical courses. In its early, localized stages, PCa is usually treated with curative intent by local therapy, such as radical prostatectomy, external beam radiation therapy, or brachytherapy. PCa is strictly dependent on androgen receptor (AR) signaling in all stages of disease, except for neuroendocrine differentiation. Androgen deprivation therapies (ADT) aimed at disrupting AR signaling by surgical or chemical castration, combined in selected cases with antiandrogens, are the standard care for locally advanced or metastatic disease. The disease may be controlled for several years, the benefit of ADT is only temporary
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