ERG expression can predict the outcome of docetaxel combinedwith androgen deprivation therapy in metastatic hormone-sensitiveprostate cancer

Küronya, Zsófia; Sükösd, Farkas; Varga, Linda; Bíró, Krisztina; Gyergyay, Fruzsina; Gergely, Lajos; Nagyiványi, Krisztián; Jorgo, Kliton; Szarvas, Tibor; Kovács, A; Laczó, Ibolya; Varga, Zoltán; Pósfai, Boglárka; Pepó, J; Maráz, Anikó

doi:10.1016/j.urolonc.2018.12.007

Cited by 7 publications

(9 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The TMPRSS2-ERG fusion is an early and one of the most common genetic abnormalities responsible for tumor invasion and progression affecting growth pathways and regulating differentiation, cell cycle, proliferation, angiogenesis and morphology in PCa (78)(79)(80). The overexpression of ERG is a biomarker of fusion, and may be related to unfavorable prognostic factors and decreased survival (80)(81)(82)(83). The incidence of fusion significantly differs between the nationalities and our results were similar to other Polish data (26,84,85).…”

Section: Discussionsupporting

confidence: 87%

Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

et al. 2021

View full text Add to dashboard Cite

BackgroundCancer stroma contains the neural compartment with specific components and action. Neural microenvironment processing includes among others axonogenesis, perineural invasion (PNI), neurosignaling, and tumor cell neural/neuroendocrine differentiation. Growing data suggest that tumor-neural crosstalk plays an important function in prostate cancer (PCa) biology. However, the mechanisms involved in PNI and axonogenesis, as well as their patho-clinical correlations in this tumor are unclear.MethodsThe present study was carried out on FFPE samples of 73 PCa and 15 benign prostate (BP) cases. Immunohistochemistry with neural markers PGP9.5, TH, and NFP was performed on constructed TMAs and selected tissue sections. The analyzed parameters of tumor innervation included small nerve density (ND) measured on pan-neural marker (PGP9.5) and TH s4tained slides, as well assessment of PNI presence and morphology. The qualitative and topographic aspects were studied. In addition, the expression of neuroendocrine marker chromogranin and NPY was assessed with dedicated indexes. The correlations of the above parameters with basic patho-clinical data such as patients’ age, tumor stage, grade, angioinvasion, and ERG status were examined.ResultsThe study showed that innervation parameters differed between cancer and BP. The neural network in PCa revealed heterogeneity, and ND PGP9.5 in tumor was significantly lower than in its periphery. The density of sympathetic TH-positive fibers and its proportion to all fibers was lower in cancer than in the periphery and BP samples. Perineural invasion was confirmed in 76% of cases, usually multifocally, occurring more commonly in tumors with a higher grade. NPY expression in PCa cells was common with its intensity often rising towards PNI. ERG+ tumors showed higher ND, more frequent PNI, and a higher stage. Moreover, chromogranin-positive cells were more pronounced in PCa with higher NPY expression.ConclusionsThe analysis showed an irregular axonal network in prostate cancer with higher neural density (panneural and adrenergic) in the surroundings and the invasive front. ND and PNI interrelated with NPY expression, neuroendocrine differentiation, and ERG status. The above findings support new evidence for the presence of autocrine and paracrine interactions in prostate cancer neural microenvironment.

show abstract

Section: Discussionsupporting

confidence: 87%

Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Based on our previous experience as well as published data reflecting PC tumor biology (Figure 1), cases of MPC were classified into three categories based on cytomorphologic and immunohistochemical features: conventional, intermediary, or HGNC 11‐13 . Conventional cases were categorized by the presence of acinar morphology, retained expression of prostatic‐specific markers, and absent neuroendocrine expression.…”

Section: Methodsmentioning

confidence: 99%

“…26,27 Finally, ERG expression is highly specific for MPC and hence of diagnostic utility and may also serve as a potential predictive marker for docetaxel response. 28 In this study, we retrospectively reviewed cases of MPC diagnosed by FNA and correlated the findings with clinicopathologic features and contemporary prostate cancer therapies including CRPC. Cases were specifically evaluated for variant morphologies or other pro-proliferative features and the impact of prior therapy on pathologic features and clinical outcome.…”

Section: Introductionmentioning

confidence: 99%

Metastatic prostate cancer diagnosed by fine‐needle aspiration: Contemporary cytopathologic and biomarker assessment with clinical correlates

Cantley

Wang

Reichert

et al. 2022

Cancer Cytopathology

View full text Add to dashboard Cite

Introduction The diagnosis of metastatic prostatic cancer (MPC) by fine needle aspiration (FNA) can usually be rendered by typical cytomorphologic and immunohistochemical (IHC) features. However, MPC diagnosis may be complicated by transformation to atypical phenotypes such as small cell carcinoma, typically under pressure from androgen deprivation therapy (ADT). Predictive and prognostic biomarkers can also be assessed by IHC. This study illustrates how careful assessment of cytologic and biomarker features may provide therapeutic and prognostic information in MPC. Design We reviewed our anatomic pathology archives for MPC diagnosed by FNA from January 2014 to June 2021. Clinical histories, cytology slides, and cell blocks were reviewed. Extensive IHC biomarker workup was performed, including markers of prostate lineage, cell‐cycle dysfunction, Ki‐67, neuroendocrine markers, PDL1, and androgen receptor splice variant 7. Cases were reclassified into three categories: conventional type, intermediary type, and high‐grade neuroendocrine carcinoma (HGNC). Results Eighteen patients were identified. Twelve had conventional MPC, including six of six ADT‐naive patients. Six of twelve (50%) with prior ADT were reclassified as intermediary or HGNC. Four intermediary cases included two with squamous differentiation and two with pro‐proliferative features. Two HGNC cases had typical small cell carcinoma cytomorphology. Expression of PDL1 was identified in two cases and ARv7 in three cases. Five of five intermediary and HGNC patients died of disease versus six of eleven with with conventional type. Conclusions Aggressive cytomorphologic variants were commonly identified in patients with prior ADT. Identification of nonconventional cytomorphology and increased proliferation can provide important prognostic information. Recognition of these changes is important for an accurate diagnosis, and the identification of high‐grade variants can affect therapeutic decision‐making. Clinically actionable biomarkers such as PDL1 and ARv7 can be assessed by IHC.

show abstract

“…These findings indicated that ERG gene fusion status is unlikely to be a predictive factor for radiation response. However, in patients suffering from metastatic CS-CaP treated with docetaxel in addition to ADT, expression of ERG was associated with favorable relapse-free survival, suggesting ERG expression may have a potential predictive value with respect to the effectiveness and outcome of docetaxel chemotherapy combined with ADT [98].…”

Section: Ar Target Gene Expression Associated Genomic Marks and Cap Treatment Responsesmentioning

confidence: 98%

Somatic Alterations Impact AR Transcriptional Activity and Efficacy of AR-Targeting Therapies in Prostate Cancer

Chauhan

Heemers

2021

Cancers

View full text Add to dashboard Cite

Inhibiting the activity of the ligand-activated transcription factor androgen receptor (AR) is the default first-line treatment for metastatic prostate cancer (CaP). Androgen deprivation therapy (ADT) induces remissions, however, their duration varies widely among patients. The reason for this heterogeneity is not known. A better understanding of its molecular basis may improve treatment plans and patient survival. AR’s transcriptional activity is regulated in a context-dependent manner and relies on an interplay between its associated transcriptional regulators, DNA recognition motifs, and ligands. Alterations in one or more of these factors induce shifts in the AR cistrome and transcriptional output. Significant variability in AR activity is seen in both castration-sensitive (CS) and castration-resistant CaP (CRPC). Several AR transcriptional regulators undergo somatic alterations that impact their function in clinical CaPs. Some alterations occur in a significant fraction of cases, resulting in CaP subtypes, while others affect only a few percent of CaPs. Evidence is emerging that these alterations may impact the response to CaP treatments such as ADT, radiation therapy, and chemotherapy. Here, we review the contribution of recurring somatic alterations on AR cistrome and transcriptional output and the efficacy of CaP treatments and explore strategies to use these insights to improve treatment plans and outcomes for CaP patients.

show abstract

ERG expression can predict the outcome of docetaxel combinedwith androgen deprivation therapy in metastatic hormone-sensitiveprostate cancer

Cited by 7 publications

References 19 publications

Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

Metastatic prostate cancer diagnosed by fine‐needle aspiration: Contemporary cytopathologic and biomarker assessment with clinical correlates

Somatic Alterations Impact AR Transcriptional Activity and Efficacy of AR-Targeting Therapies in Prostate Cancer

Contact Info

Product

Resources

About