Levels of 5α-reductase type 1 and type 2 are increased in localized high grade compared to low grade prostate cancer
Levels of 5α-reductase type 1 and type 2 are increased in localized high grade compared to low grade prostate cancer
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DOI：
10.1016/j.juro.2007.08.155
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发表时间：
2008-01-01
影响因子：
6.6
通讯作者：
Too, Catherine K. L.
中科院分区：
文献类型：
--
作者：
Thomas, Lynn N.;Douglas, Robert C.;Too, Catherine K. L.
目的：在前列腺中，睾酮通过1型和/或2型5 α-还原酶转化为二氢睾酮。虽然5 α-还原酶2型在正常前列腺中占主导地位，但1型在癌症中相对于良性组织增加。目前尚不清楚5 α-还原酶1/2型水平是否与癌症分级相关。我们比较了5 α-还原酶1型和2型的相对表达在局部高，低级别prostate cancer.Materials和方法：免疫组化5 α-还原酶1/2型进行了评估，在64例前列腺组织未经治疗的男性局限性前列腺癌。对于组织中的每种Gleason模式，估计具有中-高强度染色的肿瘤面积的百分比。结果：5 α-还原酶1型的中高染色从34例Gleason 3型癌的18.8% +/- 2.9%（平均值+/- SEM）增加到30例Gleason 4/5型癌的31.0% +/- 4.1%（p = 0.016）。5 α-还原酶2型染色从34例Gleason 3型癌症的22.9% +/- 3.0%增加到30例Gleason 4/5型癌症的39.2% +/- 4.1%（p = 0.002）。与良性前列腺增生组织相比，5 α-还原酶1型染色高3倍以上，5 α-还原酶2型染色在癌旁良性组织中显著降低（分别为p = 0.006和0.0236）。5 α-还原酶1型在癌旁良性组织中的水平高于良性前列腺增生。这些结果提高了局部高级别癌症中5 α-还原酶1型的增加可能有助于降低前列腺癌预防试验中5 α-还原酶2型选择性抑制剂非那肽对高级别前列腺癌的有效性。
Purpose: In the prostate testosterone is converted to dihydrotestosterone by 5 alpha-reductase type 1 and/or 2. Although 5 alpha-reductase type 2 is predominant in normal prostates, type 1 is increased in cancer vs benign tissue. It is unclear whether 5 alpha-reductase type 1/2 levels correlate with cancer grade. We compared the relative expression of 5a-reductase type 1 and 2 in localized high and low grade prostate cancer.Materials and Methods: Immunostaining for 5 alpha-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.Results: Moderate-high staining for 5 alpha-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 5 alpha-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 5 alpha-reductase type 1 was greater than 3-fold higher and staining for 5 alpha-reductase type 2 was significantly lower in benign tissue adjacent to cancer (p = 0.006 and 0.0236, respectively).Conclusions: Levels of 5 alpha-reductase type and 2 are increased in localized high vs low grade prostate cancer. Levels of 5 alpha-reductase type 1 are higher in benign tissue adjacent to cancer than in benign prostatic hyperplasia. These results raise the possibility that increased 5 alpha-reductase type 1 in localized high grade cancers may contribute to the decreased effectiveness of the 5 alpha-reductase type 2 selective inhibitor finasteride against high grade prostate cancer in the Prostate Cancer Prevention Trial.