Prognostic significance of plasma chromogranin a levels in patients with hormone-refractory prostate cancer treated in Cancer and Leukemia Group B 9480 study

Taplin, Mary‐Ellen; George, Daniel J.; Halabi, Susan; Sanford, Ben; Febbo, Philip G.; Hennessy, Kristen; Mihos, Christos G.; Vogelzang, Nicholas J.; Small, Eric J.; Kantoff, Philip W.

doi:10.1016/j.urology.2005.03.040

Cited by 84 publications

(60 citation statements)

References 25 publications

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“…Several investigators found that increased chromogranin A levels are associated with high-grade disease, advanced state disease and poor survival, particularly in the case of hormone-refractory cancer. [87][88][89] In addition, a number of studies showed that an elevation of serum chromogranin A preceded PSA increase as a marker of progression to hormone-refractory disease. As such, it may be possible to use chromogranin A to monitor metastatic PCa patients under androgen blockade.…”

Section: Chromogranin Amentioning

confidence: 99%

New circulating biomarkers for prostate cancer

Bensalah

Lotan

Karam

et al. 2007

Prostate Cancer Prostatic Dis

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Section: Chromogranin Amentioning

confidence: 99%

New circulating biomarkers for prostate cancer

Bensalah

Lotan

Karam

et al. 2007

Prostate Cancer Prostatic Dis

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“…7 The controversy continues with some recent studies showing an independent negative correlation between serum CgA and survival in AI CaP, 33,34 but others showing no prognostic correlation, 35 or improved outcomes with higher CgA. 36 These authors all agree that the serum CgA continues to be a valid marker of progression, but the complex biology of NED makes direct correlation with prognosis difficult.…”

Section: Products Action In Cap Referencesmentioning

confidence: 99%

Clinical implications of neuroendocrine differentiation in prostate cancer

Nelson

Cambio

Yang

et al. 2006

Prostate Cancer Prostatic Dis

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The cellular signaling pathways of the prostate play a central role in the induction, maintenance, and progression of prostate cancer (CaP). Neuroendocrine (NE) cells demonstrate attributes that suggest they are an integral part of these signaling cascades. We summarize what is known regarding NE cells in CaP focusing on NE cellular transdifferentiation. This significant event in CaP progression appears to be accelerated by androgen deprivation (AD) treatment. We examine biochemical pathways that may impact NE differentiation in a chronological manner focusing on AD therapy (ADT) as a central event in inducing androgen-independent CaP. Our analysis is limited to the common adenocarcinoma pattern of CaP and excludes small-cell and carcinoid prostatic variants. In conclusion, we speculate on the future of treatment and research in this area.

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“…Several mechanisms have been identified in this respect: neuroendocrine cells are androgen receptor negative, therefore they survive androgen deprivation; as an alternative, neuroendocrine cells produce peptides, hormones and growth factors that could stimulate the proliferation of exocrine prostate cancer cells and increase their aggressiveness through apoptosis inhibition and neoangiogenesis stimulation. [5][6][7] Two recent studies in patients with hormone-refractory disease have demonstrated an independent poor prognostic role of elevated levels of circulating chromogranin A, a marker of neuroendocrine differentiation, 8,9 although in patients with hormone naive disease a significant relationship between amount of neuroendocrine cells and disease stage and grade but not with disease-free survival and overall survival has been unequivocally proven. [10][11][12] Neuroendocrine differentiation regulatory mechanisms might play a role in the transition from an androgen-dependent to an androgen-resistant phenotype in prostate cancer, and in vivo studies, both in animals 13 and humans, 14 have shown that the neuroendocrine prostate cancer compartment increases after androgen deprivation.…”

mentioning

confidence: 99%

Human ASH1 expression in prostate cancer with neuroendocrine differentiation

et al. 2008

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Neuroendocrine differentiation in prostate cancer correlates with overall prognosis and disease progression after androgen-deprivation therapy, although its specific mechanisms are currently poorly understood. A role of Notch pathway has been reported in determining neuroendocrine phenotype of normal and neoplastic tissues. The aim of this study was to analyze whether this pathway might affect neuroendocrine differentiation in prostate cancer. Human achaete-scute homolog 1 (hASH1), a pivotal member of the Notch pathway, was investigated in 80 prostate cancers selected and grouped according to chromogranin A immunohistochemistry, as follows: prostate cancers without neuroendocrine differentiation, untreated (25 cases); prostate cancers with neuroendocrine differentiation, untreated (40 cases); prostate cancers with previous androgen-deprivation therapy, all having neuroendocrine differentiation (15 cases). Human ASH1 protein was analyzed by immunohistochemistry, whereas the presence of hASH1 mRNA transcripts was investigated on paraffin material by real-time PCR. By immunohistochemistry, hASH1 was colocalized with chromogranin A in neuroendocrine cells of normal prostatic gland. It was absent in all but one prostate cancers without neuroendocrine differentiation, whereas it was positive in 25% of prostate cancers with neuroendocrine differentiation/ untreated, with a significant correlation with the extent of neuroendocrine features (P ¼ 0.02). Moreover, comparing untreated and treated prostate cancers with neuroendocrine differentiation, a positive association with androgen-deprivation therapy was observed (P ¼ 0.01). In prostate cancers with neuroendocrine differentiation, RNA analysis confirmed the association of higher transcript levels in androgen deprivationtreated compared with untreated patients (P ¼ 0.01). In addition, hASH1 mRNA analysis in microdissected chromogranin A-positive and chromogranin A-negative areas within the same tumor demonstrated a two-to sevenfold increase of hASH1 mRNA expression in chromogranin A-positive tumor cell populations.

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Prognostic significance of plasma chromogranin a levels in patients with hormone-refractory prostate cancer treated in Cancer and Leukemia Group B 9480 study

Cited by 84 publications

References 25 publications

New circulating biomarkers for prostate cancer

New circulating biomarkers for prostate cancer

Clinical implications of neuroendocrine differentiation in prostate cancer

Human ASH1 expression in prostate cancer with neuroendocrine differentiation

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