1884 ANDROGEN RECEPTOR AND BCL-2 EXPRESSION IN PROSTATE CANCER

but not tumor related death. Additional studies on bcl-2 and other related markers are needed.

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EDITORIAL COMMENT

The molecular mechanisms governing androgen independent pros- tate cancer progression are poorly understood. One hypothesis is that androgen independent tumors survive hormone ablation by upregulating genes that protect against apoptosis, such as bcl-2. In the current study tested this hypothesis was tested by immunohis- tochemically staining transurethral resection specimens from hormone-naive and hormone-refractory patients for bcl-2 protein expression. Contrary to other published series, these authors found a much lower rate of bcl-2 positivity in untreated and treated pa- tients, suggesting that bcl-2 expression cannot be the only or even the primary mechanism underlying androgen independent progres- sion. Why these results differ from those of previous studies (refer- ences 11 and 15 in article) is unclear. Some notable features of the current patient series are that 76% had Gleason scores of 8 to 10 and that no metastatic lesions were examined. Perhaps bcl-2 expression has a more important role in metastatic androgen-independent pro- gression or in lower grade tumors, although this study does include some bcl-2 negative patients with lower grade disease. Although it seems unlikely that differences in tissue handling before fixation and therefore protein degradation could explain the discrepancies in different studies, i t would be interesting to see if bcl-2 messenger ribonucleic acid is expressed in these samples.

It is important to note that the pretreatment and posttreatment specimens in this study were not obtained from the same patients and, thus, it remains possible that bcl-2 expression is upregulated in individual patients during hormone independent progression. Also, for the same reason, this study cannot answer whether bcl-2 upregu- lation after hormonal therapy has negative prognostic value. As for androgen receptor staining, this study is consistent with other stud- ies showing an inverse relationship between grade and androgen receptor positivity. It is unclear what to make of the combined bcl-Uandrogen receptor score reported here. Although one might predict that a combination of high bcl-2 and low androgen receptor or low bcl-2 and high androgen receptor would be poor predictors (ei- ther high bcl-2 expression or high androgen receptor expression

ANDROGEN RECEPTOR AND BCL-2 EXPRESSION IN PROSTATE CANCER 1885 would be necessary for androgen independent growth), it is not evident why high bcl-2 and high androgen receptor expression would be good predictors. This observation needs to be confirmed by other investigators.

All said, I believe the major point of this article is that androgen independent prostate cancer is likely to be a heterogeneous disease with multiple molecular mechanisms. Alternative mechanisms might in- dude expression of other anti-apoptotic genes (bcl-xl and bcl-w), andro- gen receptor mutations and stimulation by other growth factors

(epidermal growth factor and 80 forth). Future basic science and trans- lational research will hopefully unravel this complex prostate cancer phenotype.

Robert E. Reiter Department of Urology UCLA School of Medicine Los Angeles, California