The significance of monoamine oxidase-A expression in high grade prostate cancer.
OBJECTIVE
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.


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.
Peehl
Donna M
DM
Department of Urology, Stanford University School of Medicine, Stanford, California, USA. dpeehl@stanford.edu
Coram
Marc
M
Khine
Htet
H
Reese
Stephen
S
Nolley
Rosalie
R
Zhao
Hongjuan
H
D000230:Adenocarcinoma / Q000097:blood / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001707:Biopsy, Needle; D015331:Cohort Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000473:pathology*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018570:Risk Assessment; D015996:Survival Rate
D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; D008995:Monoamine Oxidase; D017430:Prostate-Specific Antigen