NeuroD1 expression in human prostate cancer: can it contribute to neuroendocrine differentiation comprehension?
OBJECTIVE
Neuroendocrine differentiation is a common feature of prostate cancer (pCA). NeuroD1 is a neuronal transcription factor able to convert epithelial cells into neurons. The aim of the study is to investigate NeuroD1 expression and compare it with chromogranin-A, synaptophysin, and CD56 staining in human prostate cell lines and surgical specimens.


METHODS
We detected NeuroD1 gene expression, by duplex reverse transcriptase-polymerase chain reaction, in primary human prostate fibroblasts, in EPN, LNCaP, DU145, and PC3 cell lines before and after cAMP exposure, in 6 BPH and 11 pCA samples. Thereafter 166 paraffin sections from normal and neoplastic prostates were stained with NeuroD1, chromogranin-A, synaptophysin, and CD56 antibodies. The relationships between chromogranin-A and NeuroD1 and clinicopathologic parameters were evaluated by multivariate logistic regression analysis.


RESULTS
NeuroD1 is inactive in baseline prostate cell lines and BPHs, whereas it is actively expressed in cAMP-treated EPN, PC3, and DU145 cells. In our surgical series, positive chromogranin-A, synaptophysin, CD56, and NeuroD1 staining was detected in 26.5%, 4.3%, 3.1%, and 35.5%, respectively (difference between chromogranin-A and NeuroD1: p<0.05). The multivariate analysis showed a strong association between chromogranin-A and microscopic perineural invasion (OR: 2.49; 95%CI, 0.85-7.32; p=0.097) and a high primary Gleason score (OR: 1.96; 95%CI, 1.14-3.39; p=0.015), whereas NeuroD1 expression strictly correlated to microscopic perineural invasion (OR: 2.97; 95%CI, 1.05-8.41; p=0.04).


CONCLUSIONS
Expression of NeuroD1 versus chromogranin-A is more frequent in pCA, and correlates to increased indicators of malignancy in moderately to poorly differentiated pCA, and could be involved in the pathophysiology of the neuroendocrine differentiation of pCA.
Cindolo
Luca
L
Urology Unit, "G. Rummo" Hospital, Benevento, Italy. lucacindolo@virgilio.it
Franco
Renato
R
Cantile
Monica
M
Schiavo
Giulia
G
Liguori
Giuseppina
G
Chiodini
Paolo
P
Salzano
Liugi
L
Autorino
Riccardo
R
Di Blasi
Arturo
A
Falsaperla
Mario
M
Feudale
Elisa
E
Botti
Gerardo
G
Gallo
Antonio
A
Cillo
Clemente
C
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D053379:Chromogranin A / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D053379:Chromogranin A; D012334:RNA, Neoplasm; C093970:NEUROD1 protein, human