The Significance of Monoamine Oxidase-A Expression in High Grade Prostate Cancer

Abstract

Purpose-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.Materials and Methods-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.Results-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.Conclusions-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. Keywordsprostate; monoamine oxidase; neoplasm recurrence, local; adenocarcinoma; CD44 protein, humanThe presence of Gleason grades 4 and/or 5 cancer in primary adenocarcinoma of the prostate is associated with a poor outcome following radical prostatectomy. 1 The primary determinant of failure to cure prostate cancer by surgery is the percent of Gleason grade 4/5 present in the largest (index) cancer. 2 Individuals in whom cancer is composed entirely of Gleason grade 3 have a greater than 95% chance of being cured by surgery. In contrast, for approximately every 10% increase in the percent of grade 4/5 cancer present at surgery there is a 10% biochemical The functions of MAO-A in the nervous system have been extensively studied and inhibitors of its activity have therapeutic value in neurological diseases. 4 However, MAO-A actions in other tissues are not as well understood. In studies to reveal the biological role of MAO-A in prostate cancer we observed that MAO-A is also highly expressed in basal but not in secretory cells of the normal prostatic epithelium. 5 Furthermore, using a primary cell culture model we noted that...

Increased expression of monoamine oxidase A is associated with epithelial to mesenchymal transition and clinicopathological features in non-small cell lung cancer

“…However, conflicting results were reported across different types of cancer, including prostate cancer (24)(25)(26)(27)(28)(29)(30), HCC (31), and cholangiocarcinoma (32). MAOA was demonstrated as being highly expressed in high-grade aggressive prostate cancer, and capable of mediating prostate tumorigenesis and metastasis (24)(25)(26)(27). Recently, MAOA was reported as a novel decision maker in apoptosis and autophagy processes occurring within hormone refractory neuroendocrine prostate cancer cells (28).…”

“…Previous studies have demonstrated that prostate cancer and HCC exhibit completely different MAOA expression levels (24,31), and to date, MAOA expression has not been reported in NSCLC. To investigate the expressions of MAOA and EMT markers in NSCLC tissues, immunohistochemical staining was performed in 45 pairs of NSCLC and patient-matched non-tumor adjacent lung tissues.…”

“…The functions of MAOA have been extensively studied in the context of neurological disorders, including mental depression, aggressive behaviors, and Parkinson's disease (22,23). Recent studies have indicated the role of MAOA in the progression of prostate cancer (24)(25)(26)(27)(28)(29)(30), hepatocellular carcinoma (HCC) (31), and cholangiocarcinoma (32). High Gleason grade or poorly differentiated prostate cancer exhibited increased MAOA expression (24), and the increased MAOA promoted prostate cancer metastasis (25,26 (25).…”

Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis

“…In the last several decades, MAOA has been widely studied in the context of neuropsychiatric disorders, such as aggressive behaviors and mental depression (3,5). Recently, a significant correlation was established between increased levels of MAOA expression and high Gleason grade or poorly differentiated human prostate tumors (7,8). MAOA is exclusively expressed in the epithelial cells of prostatic glands with relatively low levels in stromal counterparts (9).…”

Influence of concurrent medications on outcomes of men with prostate cancer included in the TAX 327 study

“…38 In vitro proliferation experiments. 37 Erythropoietin May promote growth of prostate cancer cells.…”