Correlation of three immunohistochemically detected markers of neuroendocrine differentiation with clinical predictors of disease progression in prostate cancer

Abstract

BackgroundThe importance of immuno-histological detection of neuroendocrine differentiation in prostatic adenocarcinoma with respect to disease at presentation and Gleason grade is gaining acceptance. There is limited literature on the relative significance of three commonly used markers of NE differentiation i.e. Chromogranin A (CgA), Neuron specific enolase (NSE) and Synaptophysin (Syn). In the current work we have assessed the correlation of immuno-histological detection of neuroendocrine differentiation in prostatic adenocarcinoma with respect to disease at presentation and Gleason grade and to determine the relative value of various markers.Materials and methodsConsecutive samples of malignant prostatic specimens (Transurethral resection of prostate or radical retropubic prostatectomy) from 84 patients between January 1991 and December 1998 were evaluated by immunohistochemical staining (PAP technique) using selected neuroendocrine tumor markers i.e. Chromogranin A (CgA), Neuron specific enolase (NSE), and Synaptophysin (Syn). According to the stage at diagnosis, patients were divided into three groups. Group (i) included patients who had organ confined disease, group (ii) included patients with locally invasive disease, and group (iii) with distant metastasis. NE expression was correlated with Gleason sum and clinical stage at presentation and analyzed using Chi-Square test and one way ANNOVA.ResultsThe mean age of the patients was 70 ± 9.2 years. Group I had 14 patients, group II had 31 patients and group III had 39 patients. CgA was detected in 33 cases, Syn in 8 cases, and NSE in 44 cases. Expression of CgA was seen in 7% of group I, 37% in group II and 35% of group III patients (p 0.059). CgA (p 0.024) and NSE (p 0.006) had a significantly higher expression with worsening Gleason grade.ConclusionCgA has a better correlation with disease at presentation than other markers used. Both NSE and CgA had increasing expression with worsening histological grade this correlation has a potential for use as a prognostic indicator. Limitations in the current work included small number and retrospective nature of work. The findings of this work needs validation in a larger cohort.

Regulation of neuroendocrine differentiation by AKT/hnRNPK/AR/β‐catenin signaling in prostate cancer cells

“…Serum chromogranin A, a NE differentiation marker, has been proposed as an indicator of advanced prostate cancer in some patients who do not have elevated serum PSA. 8,[33][34][35] In the present study, by analyzing molecular pathways altered during NE differentiation, we have identified a small cluster of putative predictive markers that could identify PC at high risk of resistance to therapy and might serve as therapeutic targets for prevention and to slow disease progression. AKT, an important signaling molecule in mammalian cells, is considered a key player in many tumors including PC 36 and transgenic mice expressing activated AKT in the prostate develop intraepithelial neoplasia, 37 a precursor lesion of PC.…”

“…7 The importance of immuno-histological detection of NED in prostatic adenocarcinoma with respect to disease at presentation and Gleason grade is gaining acceptance, and a correlation of immunohistochemically detected markers of neuroendocrine differentiation with clinical predictors of disease progression in prostate cancer has been reported. 8 Using proteomic analysis of the nuclear matrix, we previously reported that hnRNP K, a member of the hnRNP family with pleiotropic functions, 9-12 was overexpressed in PC specimens with involvement of seminal vesicles and that its expression level was closely correlated with Gleason score …”

For Which Cancer Types can Neuron-Specific Enolase be Clinically Helpful in Turkish Patients?

“…In 84 prostate cancer patients, Ather et al evaluated the correlation of immunohistological detection of neuroendocrine differention marker NSE with Gleason grade. They found that NSE had a significantly higher expression with worsening Gleason grade (Ather et al, 2008). Humez et al (2006) observed that neuroendocrine differentiation was associated with NSE expression and this was important for the prostate cancer progression and hormonal-therapy failure.…”

The New Combination Docetaxel, Prednisone and Curcumin in Patients with Castration-Resistant Prostate Cancer: A Pilot Phase II Study

“…The clinical significance of these markers has been analyzed in several studies; CgA and NSE were shown to have an independent prognostic significance in prostate cancer [22]. CgA appears to be the best sensitive marker for detecting NE differentiation [22]. Ferrero-Poüs et al [23] found that patients resistant to androgen-suppressive treatments and with elevated PSA had an increase in CgA and NSE in 62 and 29% of cases, respectively.…”

“…Serum levels of NE markers might reflect the NE activity of prostate carcinoma [21]. The clinical significance of these markers has been analyzed in several studies; CgA and NSE were shown to have an independent prognostic significance in prostate cancer [22]. CgA appears to be the best sensitive marker for detecting NE differentiation [22].…”