Elsevier

Urology

Volume 51, Issue 4, April 1998, Pages 585-589
Urology

Adult Urology
Neuroendocrine Differentiation in Prostatic Carcinoma During Hormonal Treatment

https://doi.org/10.1016/S0090-4295(97)00684-5Get rights and content

Abstract

Objectives. Neuroendocrine differentiation (NED) is a common feature in adenocarcinoma of the prostate. Several studies suggest that NED may have a major impact on cancer progression as neuroendocrine (NE) secretory products have been shown to possess growth stimulatory effects. NED has also been proposed to constitute part of the mechanism by which a prostate cancer cell progresses toward androgen independence as NE tumor cells have been demonstrated to be devoid of androgen receptor immunoreactivity. In this retrospective study, we evaluated NED status in prostate cancer specimens from patients undergoing androgen ablation therapy.

Methods. The degree of NED in transurethral resection of the prostate (TURP) samples from 53 patients with prostate cancer was investigated by immunocytochemistry using polyclonal rabbit immunoglobin G (IgG) against chromogranin A (CgA). Changes in NED with time were determined by a manual semiquantitative cell counting method.

Results. During androgen withdrawal therapy, 21 tumors (40%) displayed increased NED concomitant with histopathologic tumor progression, whereas 29 carcinomas (55%) showed no change in NED status. However, a majority of the histopathologically unchanged tumors displayed marked NED at the first TURP and an increase in NED was by definition not possible. In only 3 cases (5%) was a decrease in NED observed with time.

Conclusions. Androgen ablation therapy may be a contributing factor to the increase in NED of prostatic adenocarcinoma with time, and our findings imply that androgen withdrawal therapy enhances the selection and progression of NED, androgen-independent tumor cells.

Section snippets

Patients and Tissue Specimens

Repeated transurethral resection of the prostate (TURP) samples from 53 men with histopathologically confirmed adenocarcinoma of the prostate were obtained at intervals during androgen withdrawal treatment; 18 men underwent orchiectomy and 35 men underwent medical castration. The mean follow-up was 4.6 years. Each patient underwent 2 to 4 transurethral resections (mean 2.6), and the mean age of the patients at the first TURP was 71 years (range 52 to 87).

The patient cohort consisted of two

Results

During the follow-up period, 25 of the prostate carcinomas (47%) were dedifferentiated with time. In 26 tumors (49%), no change in histopathologic differentiation grade was observed as assessed using the WHO classification system. An increase in tumor differentiation grade was noted in 2 cases (4%) (Table II). However, it should be noted that the vast majority of tumors not showing any change in histopathologic differentiation over time (22 of 26) were poorly differentiated at the first TURP

Comment

NED in prostate cancer has been associated with tumor progression, androgen independence, and a poor prognosis.7, 8, 9, 10, 11, 13, 14 In addition, several studies have demonstrated prostatic NE cells to be devoid of androgen receptor immunoreactivity, and NED has been proposed to constitute part of the mechanism by which a prostate cancer cell progresses toward androgen independence.11, 13, 14, 18, 19 Furthermore, in a recent study, Noordzij et al.[26] found increased NED after androgen

Conclusions

NE tumor cells in prostate cancer in men are considered to be androgen independent as they do not express the androgen receptor. Furthermore, there is accumulated evidence that NED in adenocarcinoma of the prostate is associated with androgen independence and poor prognosis.

The present study shows that prostate cancer specimens become enriched in NE cells with time during androgen withdrawal therapy. These data suggest that hormonal ablation therapy enhances the selection and progression of

References (41)

  • X Li et al.

    Parathyroid hormone-related peptide is a downstream target for ras and src activation

    J Biol Chem

    (1994)
  • E Rozengurt et al.

    Early signals underlying the induction of the c-fos and c-myc genes in quiescent fibroblastsstudies with bombesin and other growth factors

    Prog Nucl Acid Res Mol Biol

    (1988)
  • PA di Sant’Agnese

    Neuroendocrine differentiation in carcinoma of the prostate

    Cancer

    (1992)
  • PJM Tutton et al.

    Biogenic amines as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review)

    Anticancer Res

    (1987)
  • CJ Dalsgård et al.

    Neuropeptides as growth factorsPossible roles in human diseases

    Regul Pept

    (1989)
  • M Bologna et al.

    Bombesin stimulates growth of human prostatic cancer cells in vitro

    Cancer

    (1989)
  • MC Dauge et al.

    APUD type endocrine tumor of the prostateincidence and prognosis in association with adenocarcinoma

  • B Tetu et al.

    Small cell carcinoma of the prostatepart I.A clinicopathologic study of 20 cases

    Cancer

    (1987)
  • UA Almagro et al.

    Argyrophilic, “carcinoid-like” prostatic carcinoma

    Arch Pathol Lab Med

    (1986)
  • RJ Cohen et al.

    Prostatic carcinomahistological and immunohistological factors affecting prognosis

    Br J Urol

    (1990)
  • Cited by (132)

    View all citing articles on Scopus
    View full text