The significance of monoamine oxidase-A expression in high grade prostate cancer.
The significance of monoamine oxidase-A expression in high grade prostate cancer.
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单胺氧化酶A表达在高级前列腺癌中的重要性。
DOI：
10.1016/j.juro.2008.07.019
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发表时间：
2008-11
期刊：
影响因子：
--
通讯作者：
Zhao H
中科院分区：
文献类型：
--
作者：
Peehl DM;Coram M;Khine H;Reese S;Nolley R;Zhao H
Gleason 4/5级前列腺癌是根治性前列腺切除术后复发的决定因素。与3级癌症相比，单胺氧化酶-A在4/5级癌症中过度表达。单胺氧化酶-A也由正常基底细胞表达，体外研究表明其功能是抑制分泌分化。因此，4/5级癌症中的单胺氧化酶-A可能反映了向基底细胞样表型的去分化。我们研究了单胺氧化酶-A表达是否与另一种基底细胞蛋白CD 44在高级别癌症中相关，以及是否与侵袭性表型相关。共133个4/5级档案癌症的队列，以前用于评估组织形态学变量的预后意义进行了单胺氧化酶-A和CD 44免疫组化标记。确定蛋白质、组织形态学和临床变量的斯皮尔曼等级相关性。单变量和多变量值的每个变量作为生化复发的决定因素进行了评估的逻辑回归。单胺氧化酶-A表达与CD 44相关。生化复发也没有预后。而单胺氧化酶A表达与术前血清前列腺特异性抗原及4/5级癌的百分比呈正相关。单胺氧化酶-A和CD 44的同时表达表明，4/5级癌症可能是基底细胞样的性质，尽管缺乏其他经典的基底细胞生物标志物，如细胞角蛋白5和14，和p63。单胺氧化酶-A表达与前列腺特异性抗原和4/5级癌症百分比的相关性表明，单胺氧化酶-A可能有助于高级别癌症的生长，并且靶向单胺氧化酶-A的抗抑郁药物可能在治疗前列腺癌中具有应用。
Gleason grade 4/5 prostate cancer is a determinant for recurrence following radical prostatectomy. Monoamine oxidase-A is over expressed in grade 4/5 compared to grade 3 cancer. Monoamine oxidase-A is also expressed by normal basal cells and in vitro studies suggest that its function is to repress secretory differentiation. Therefore, monoamine oxidase-A in grade 4/5 cancer might reflect dedifferentiation to a basal cell-like phenotype. We investigated whether monoamine oxidase-A expression correlates with another basal cell protein, CD44, in high grade cancer and whether either is associated with an aggressive phenotype. A total of 133 grade 4/5 archival cancers from a cohort previously used to evaluate the prognostic significance of histomorphological variables were scored for monoamine oxidase-A and CD44 immunohistochemical labeling. Spearman rank correlations of the proteins, and histomorphological and clinical variables were determined. The univariate and multivariate value of each variable as a determinant of biochemical recurrence was assessed by logistic regression. Monoamine oxidase-A expression correlated with CD44. Neither was prognostic for biochemical recurrence. However, monoamine oxidase-A expression positively correlated with preoperative serum prostate specific antigen and the percent of grade 4/5 cancer. Concurrent expression of monoamine oxidase-A and CD44 suggests that grade 4/5 cancer may be basal cell-like in nature, despite the absence of other classic basal cell biomarkers such as cytokeratins 5 and 14, and p63. The correlation of monoamine oxidase-A expression with prostate specific antigen and the percent of grade 4/5 cancer suggests that monoamine oxidase-A may contribute to growth of high grade cancer and that antidepressant drugs that target monoamine oxidase-A may have applications in treating prostate cancer.
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