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Park, Park, Kim, Gang, Song, and Park: Significance of Neuroendocrine Cell Differentiation in Specimens from Patients with Prostate Cancer
Original Articles

Korean J Urol 2008;49(7):585-591.

Published online: 19 January 2008

DOI: https://doi.org/10.4111/kju.2008.49.7.585

Significance of Neuroendocrine Cell Differentiation in Specimens from Patients with Prostate Cancer

Chang Hoo Park, Chang Myeon Park, Han Kwon Kim, Kil Hyeon Gang1, Jae Seok Song2, Jong Yeon Park

From the Departments of Urology and College of Medicine, Ulsan University, College of Medicine, Kwandong University, Gangneung, Korea

1Pathology, Gangneung Asan Hospital, College of Medicine, Ulsan University, College of Medicine, Kwandong University, Gangneung, Korea

2Department of Preventive Medicine, College of Medicine, Ulsan University, College of Medicine, Kwandong University, Gangneung, Korea

Received 7 April 200829 May 2008

Copyright © 2008 The Korean Urological Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

The neuroendocrine cell (NEC) is one of the constitutional cells found in the prostate gland; these cells secret neurotransmitters. These neuroendocrine products have been associated with prostate cancer progression. We evaluated the significance of neuroendocrine differentiation (NED) in radical prostatectomy specimens.

Materials and Methods

We studied 45 patients who underwent bilateral pelvic lymphadenectomy and radical prostatectomy. The patients were classified into three groups according to their pathological stage. Group A included cases with organ confined tumors, Group B local advanced tumors and Group C cases had any T stage and lymph node metastasis. The cellular expression of chromogranin A in matched samples from the same patients was evaluated by immunohistochemical staining using commercially available monoclonal antibodies.

Results

Sixteen (35.6%) tumors had chromogranin A stained cells. Chro-mogranin A immunoreactivity was greatest in cases with lymph node involvement (75.0%) compared to those with primary prostate cancer (5.9% in group A and 37.5% in group B). Pathologically advanced tumors or tumors with the highest histological grades were associated with increased NED. The median staining score was 0 in Group A, 0 in Group B and 1 in Group C. The logistic regression analysis the odds ratio for group C cases showed a relative risk of 32.07 (95% CI: 2.783-369.416) for NED compared to Group A. An increased prostate-specific antigen (PSA) and Gleason score were also associated with the NED.

Conclusions

The degree of NEC immunohistochemical staining using the chromogranin A monoclonal antibody was marginally useful for predicting the outcome in prostate cancer patients after radical prostatectomy, especially in node positive patients. However, it is important to determine a therapeutic plan for patients with low PSA and internal organ metastasis.

Keywords: Prostate cancer, Neuroendocrine differentiation, Prognosis

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Fig. 1.
(A) The findings with a neuroendocrine differentiation score of 1 (stained cells ＜10%). Immunoreactive neoplastic cells are scattered (x100). (B) The findings with a neuroendocrine differentiation score of 3 (stained cell ＞20%). Numerous cancer cells with immunoreactivity were identified.
kju-49-585f1.tif
Fig. 2.
(A) Relationship between neuroendocrine differentiation and clinical stage (by ANOVA test). (B) Relationship between neuroendocrine differentiation and histological grade (by Student’s t-test).
kju-49-585f2.tif
Table 1.
Patient characteristics
Group A Group B Group C
No. of patients 17 16 12
Age (mean±SD) 67.29±9.61 66.81±3.37 67.00±6.16
Follow up
Duration
(Months) 24.82±22.35 45.40±40.31 21.17±15.46
(mean±SD)
Initial PSA (mean±SD) 6.07±3.37 15.71±11.52 76.00±158.48
Death 0 1 (NEDscore; 3) 2 (NEDscore; 3)
PSA at Death 24.9ng/ml 1;13.9ng/ml
1;3.6ng/ml

Group A: pathologic stage (T2 a, b, c NoMo), Group B: pathologic stage (T3 a, b NoMo), Group C: pathologic stage (T2-4N1-3Mo), PSA: prostate-specific antigen, NED: neuroendocrine differentiation

Table 2.
The characteristics among the group of patients with regard to NED
Group A Group B Group C p-value*
PSM (%) 7/17 (41.9) 13/16 (81.6) 10/11 (90.9) 0.0083
Progression (%) 2/17 (11.7) 4/16 (25.0) 3/12 (25.0) 0.5228
NED score
1 (%) 1/17 (5.88) 4/16 (25.0) 6/12 (50.0) 0.0050
2 (%) 0 (0.0) 0 (0.0) 0 (0.0)
3 (%) 0 (0.0) 2/16 (12.5) 3/12 (25.0)
Total (%) 1/17 (5.88) 6/16 (37.5) 9/12 (75.0)
NED amount
Low (%) 0 (0.0) 3/16 (18.75) 3/12 (25.0) 0.0040
High (%) 1/17 (5.88) 3/16 (18.75) 6/12 (50.0)
Total (%) 1/17 (5.88) 6/16 (37.5) 9/132 (75.0)

PPSM: positive surgical margin, NED: neuroendocrine differen tiation, *by chi-square test

Table 3.
The results of the logistic regression analysis (odds ratio of each stage according to each of the parameters)
PSA
Group B 1.251 (1.045-1.497)
Group C 1.300 (1.019-1.658)
Gleason score
Group B 1.847 (1.035-3.295)
Group C 18.869 (1.839-193.622)
NED score
Group B 6.688 (0.728-61.438)
Group C 32.066 (2.783-369.416)
NED count
Group B 3.147 (0.823-12.042)
Group C 7.853 (1.834-33.623)
NED distribution type
Group B 7.479 (0.889-62.941)
Group C 33.301 (3.046-364.016)

All odds ratio was obtained by reference group as group A. PSA: prostate-specific antigen, NED: neuroendocrine differentiation

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