Thomas Lynn N, Douglas Robert C, Lazier Catherine B, Gupta Rekha, Norman Richard W, Murphy Paul R, Rittmaster Roger S, Too Catherine K L
Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada.
J Urol. 2008 Jan;179(1):147-51. doi: 10.1016/j.juro.2007.08.155. Epub 2007 Nov 13.
In the prostate testosterone is converted to dihydrotestosterone by 5alpha-reductase type 1 and/or 2. Although 5alpha-reductase type 2 is predominant in normal prostates, type 1 is increased in cancer vs benign tissue. It is unclear whether 5alpha-reductase type 1/2 levels correlate with cancer grade. We compared the relative expression of 5alpha-reductase type 1 and 2 in localized high and low grade prostate cancer.
Immunostaining for 5alpha-reductase type 1/2 was evaluated in 64 prostate tissues from untreated men with localized prostate cancer. The percent of tumor area with moderate-high intensity staining was estimated for each Gleason pattern in the tissues. Adjacent benign tissue was evaluated in 26 prostate cancer specimens.
Moderate-high staining for 5alpha-reductase type 1 increased from 18.8% +/- 2.9% (mean +/- SEM) in 34 Gleason pattern 3 cancers to 31.0% +/- 4.1% in 30 Gleason pattern 4/5 cancers (p = 0.016). Staining for 5alpha-reductase type 2 increased from 22.9% +/- 3.0% in 34 Gleason pattern 3 cancers to 39.2% +/- 4.1% in 30 Gleason pattern 4/5 cancers (p = 0.002). Compared to benign prostatic hyperplasia tissues staining for 5alpha-reductase type 1 was greater than 3-fold higher and staining for 5alpha-reductase type 2 was significantly lower in benign tissue adjacent to cancer (p = 0.006 and 0.0236, respectively).
Levels of 5alpha-reductase type 1 and 2 are increased in localized high vs low grade prostate cancer. Levels of 5alpha-reductase type 1 are higher in benign tissue adjacent to cancer than in benign prostatic hyperplasia. These results raise the possibility that increased 5alpha-reductase type 1 in localized high grade cancers may contribute to the decreased effectiveness of the 5alpha-reductase type 2 selective inhibitor finasteride against high grade prostate cancer in the Prostate Cancer Prevention Trial.
在前列腺中，睾酮通过1型和/或2型5α-还原酶转化为二氢睾酮。虽然2型5α-还原酶在正常前列腺中占主导，但在癌组织与良性组织中，1型5α-还原酶的含量有所增加。目前尚不清楚1型/2型5α-还原酶水平是否与癌症分级相关。我们比较了局限性高分级和低分级前列腺癌中1型和2型5α-还原酶的相对表达。
对64例未经治疗的局限性前列腺癌男性患者的前列腺组织进行1型/2型5α-还原酶免疫染色评估。估计组织中每个Gleason分级模式下中高强度染色的肿瘤面积百分比。在26例前列腺癌标本中评估相邻的良性组织。
1型5α-还原酶的中高强度染色在34例Gleason分级3级癌症中从18.8%±2.9%（均值±标准误）增加到30例Gleason分级4/5级癌症中的31.0%±4.1%（p = 0.016）。2型5α-还原酶的染色在34例Gleason分级3级癌症中从22.9%±3.0%增加到30例Gleason分级4/5级癌症中的39.2%±4.1%（p = 0.002）。与良性前列腺增生组织相比，癌旁良性组织中1型5α-还原酶的染色强度高出3倍多，而2型5α-还原酶的染色强度显著降低（分别为p = 0.006和0.0236）。
局限性高分级前列腺癌中1型和2型5α-还原酶的水平高于低分级前列腺癌。癌旁良性组织中1型5α-还原酶的水平高于良性前列腺增生。这些结果提示，局限性高分级癌症中1型5α-还原酶的增加可能导致在前列腺癌预防试验中2型5α-还原酶选择性抑制剂非那雄胺对高分级前列腺癌的疗效降低。
