Clusterin as a possible predictor for biochemical recurrence of prostate cancer following radical prostatectomy with intermediate Gleason scores: a preliminary report

Abstract

Disease recurrence following radical prostatectomy is a major concern in prostate cancer patients. Gleason scores are useful in predicting recurrence. Low Gleason scores are usually associated with long disease-free intervals, while high Gleason scores are suggestive of early recurrence. However, prediction of recurrence has been difficult with intermediate Gleason scores. Clusterin is a ubiquitous secretory sulfated glycoprotein. It is also an antiapoptotic mediator in prostate cancer. The objective of the present study is to determine if clusterin can serve as a predictive biomarker for recurrence of prostate cancer with intermediate Gleason scores in patients following radical prostatectomy. Prostatic specimens with Gleason score of 6 (3+3) or 7 (3+4) were obtained from the archival bank. Three groups of specimens were investigated. The first group was from nine patients who developed recurrent disease according to a persistent rise of serum PSA within 3 years following radical prostatectomy. Those in the second group and the third group were from patients who showed no evidence of disease recurrence for at least 5 y (11 patients) and 10 y (eight patients), respectively following the surgery. Histological sections were subjected to immunohistochemical staining using a monoclonal antibody specific for clusterin. The staining intensity was scored as 0, 1, 2, and 3, with 0 being no staining, 1 showing less than 25% positive staining, 2 being 25-50% positive, and 3 showing greater than 75% positive staining. One-way ANOVA with Bonferroni correction was used for statistical analysis. Evaluation of the scores of clusterin staining was carried out according to four specific areas in each specimen. They were (a) benign epithelial cells, (b) malignant epithelial cells (cancer epithelia), (c) stromal cells surrounding benign cells, and (d) stromal cells surrounding malignant cells (cancer stroma). Staining score in prostatic epithelial cells, benign as well as malignant, showed no significant relationship among the three patient groups. However, when staining scores in stromal cells were compared, there was a significant difference between patients with recurrent disease and those showed no evidence of disease recurrence for at least 10 y. Results of this preliminary study support the important role of clusterin in the stromal component for prostate cancer progression. Clusterin immunostaining may be useful to aid the prediction of chance of disease recurrence in patients with Gleason score 6 or 7 prostate cancer following radical prostatectomy. Further studies with a large number of cases are warranted to verify this preliminary finding.

Figure 1

Clusterin immunostaining in benign epithelial cells, prostate cancer cells, and in stromal cells. (a–c) Examples of clusterin staining in benign prostatic epithelial cells in prostatectomy specimens: (a) An example of staining score of 1, in which less than 25% of epithelial cells showed positive staining for clusterin. (b) An example of staining score of 2, in which 25–75% of epithelial cells showed positive staining for clusterin. (c) An example of staining score of 3, in which more than 75% of epithelial cells showed positive staining for clusterin. (d–f) Examples of clusterin staining in malignant prostatic epithelial (prostate cancer) cells: (d) An example of staining score of 1, in which less than 25% of cancer cells showed positive staining for clusterin. (e) An example of staining score of 2, in which 25–75% of cancer cells showed positive staining for clusterin. (f) An example of staining score of 3, in which more than 75% of cancer cells showed positive staining for clusterin. (g–i) Examples of clusterin staining in stromal cells of prostate cancer specimens: (g) An example of staining score of 1, in which less than 25% of stromal cells showed positive staining for clusterin. (h) An example of staining score of 2, in which 25–75% of stromal cells showed positive staining for clusterin. (i) An example of staining score of 3, in which more than 75% of stromal cells showed positive staining for clusterin.