Relationship between neuroendocrine features and prognostic parameters in human prostate adenocarcinoma

Bollito, Enrico; Berruti, Alfredo; Bellina, M.; Mosca, Alessandra; Leonardo, Eugenio; Tarabuzzi, R.; Cappia, Susanna; Mari, M.; Tampellini, Marco; Fontana, Dario; Gubetta, L; Angeli, Alberto; Dogliotti, Luigi

doi:10.1093/annonc/12.suppl_2.s159

Cited by 57 publications

(40 citation statements)

References 23 publications

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“…Immunohistochemistry is highly specific, but its sensitivity may be influenced by sampling errors. The observed correlation between immunohistochemical CgA and pathological Gleason score, possibly reflecting the increased invasiveness of tumors with NED, is in agreement with Bollito's conclusions (18). In our series a significant correlation was found between preoperative serum CgA levels and either pathological tumor stage or pathological Gleason score.…”

Section: Discussionsupporting

confidence: 92%

“…Contrary to what has been reported by others (7,18,23), we were unable to find a significant correlation of preoperative serum CgA and its immunohistochemical expression with serum PSA, thereby suggesting a different behavior of neuroendocrine cells with respect to the (24,25), serum NSE in our series did not seem to be a useful tumor marker of NED in organ-confined CaP. Our data are in line with those reported by Slodkowska et al, who stated that NSE expression in the tumor and a mild increase in serum NSE are poor markers for distinguishing NED in non-small cell lung carcinomas (26).…”

Section: Discussioncontrasting

confidence: 77%

“…These data are not completely in line with the 45% and 50% reported by Bollito and Di Sant'Agnese, respectively (18,19), but our analysis involved only organ-confined CaP with a limited number of neuroendocrine cells. We demonstrated that the extent of NED strongly correlated with pathological disease stage, which is in agreement with other reports (18)(19)(20). Furthermore, because we used the same CgA assay as Sciarra et al, we can exclude any discordance due to the use of different kits (21,22).…”

Section: Discussioncontrasting

confidence: 66%

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The Possible Role of Chromogranin A as a Prognostic Factor in Organ-Confined Prostate Cancer

Grimaldi¹,

Valotto

Barbina

et al. 2006

Int J Biol Markers

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ABSTRACT:The clinical significance of neuroendocrine differentiation in patients who have undergone surgery for localized prostate cancer is still unclear. The aims of this study were to assess the relationship between serum neuroendocrine markers and well-known prognostic factors in prostate cancer (pathological staging, definitive Gleason score and serum PSA) and to search for correlations between serum chromogranin A (CgA) levels and pathological findings. Forty-one consecutive patients who had undergone radical retropubic prostatectomy for clinically localized prostate cancer were evaluated. Serum PSA, CgA and neuron-specific enolase were measured immediately before surgery. Twenty-six surgical specimens were phenotypically and immunohistochemically evaluated using an antibody against CgA.

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Section: Discussionsupporting

confidence: 92%

Section: Discussioncontrasting

confidence: 77%

Section: Discussioncontrasting

confidence: 66%

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The Possible Role of Chromogranin A as a Prognostic Factor in Organ-Confined Prostate Cancer

Grimaldi¹,

Valotto

Barbina

et al. 2006

Int J Biol Markers

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“…The major point of this manuscript is to demonstrate that despite apparent loss of Bcl-2 protein expression, cells are still androgen-independent and apoptosis-resistant (DU-145 and specimens from patients with androgen-independent prostate cancer). Bcl-2 protein expression was regained in LNCaP-UR NE cells after extended growth in charcoal-stripped serum suggesting that NE-like cells, which are commonly found localized with high-grade tumors 22 may contribute to the progression to androgen-unresponsiveness in prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Androgen signaling and post-transcriptional downregulation of Bcl-2 in androgen-unresponsive prostate cancer

Rothermund

Gopalakrishnan

Vishwanatha

2004

Prostate Cancer Prostatic Dis

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We previously characterized the LNCaP prostate cancer progression model and showed that despite loss of Bcl-2 protein in the androgen-unresponsive LNCaPunresponsive (UR) cells, these cells maintained an increased resistance to the induction of apoptosis. Since the loss of Bcl-2 protein coincided with the progression to androgen-unresponsiveness, we sought to determine if Bcl-2 expression was regulated through androgen signaling pathways. LNCaPresponsive (R) and -UR cells grown in charcoal-stripped serum conditions for 3 months differentiated to a neuroendocrine (NE)-like morphology. Under these conditions, LNCaP-UR cells regained Bcl-2 protein expression, and LNCaP-R cells overexpressed Bcl-2. Chronic exposure to casodex resulted in differentiation of both LNCaP-R and -UR cells to the NE-type morphology accompanied by a marked downregulation of Bcl-2 protein, while Bax protein levels were unchanged. Downregulation of Bcl-2 was post-transcriptional since Bcl-2 message levels were unchanged in LNCaP cells treated with casodex. These data suggest that Bcl-2 is post-transcriptionally modulated by androgen signaling pathways in LNCaP cells.

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“…[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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Relationship between neuroendocrine features and prognostic parameters in human prostate adenocarcinoma

Abstract: These data support the concept that NE differentiation in human prostate cancer has a negative prognostic significance. Circulating CgA levels reflect immunohistochemical findings.

Cited by 57 publications

References 23 publications

The Possible Role of Chromogranin A as a Prognostic Factor in Organ-Confined Prostate Cancer

The Possible Role of Chromogranin A as a Prognostic Factor in Organ-Confined Prostate Cancer

Androgen signaling and post-transcriptional downregulation of Bcl-2 in androgen-unresponsive prostate cancer

Human ASH1 expression in prostate cancer with neuroendocrine differentiation

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