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Aberrant expression of cystatin C in prostate cancer is associated with neuroendocrine differentiation
Author(s) -
JIBORN THOMAS,
ABRAHAMSON MAGNUS,
GADALEANU VIRGIL,
LUNDWALL ÅKE,
BJARTELL ANDERS
Publication year - 2006
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2006.06345.x
Subject(s) - neuroendocrine differentiation , prostate cancer , cystatin c , cancer research , prostate , expression (computer science) , oncology , medicine , biology , cancer , computer science , renal function , programming language
OBJECTIVE To investigate the expression of cystatin C and the relationship with neuroendocrine differentiation and proliferation in benign and malignant prostatic tissues, as cystatin C, the most important inhibitor of human lysosomal cysteine proteases, is considered to be a major regulator of pathological protein degradation in inflammatory and neoplastic diseases. MATERIALS AND METHODS Immunoreactivity for cystatin C, prostate‐specific antigen, Ki‐67 and the neuroendocrine marker chromogranin A was examined in whole‐mount radical prostatectomy specimens and using tissue microarrays. Cystatin C in tissue homogenates was analysed by Western blotting and enzyme‐linked immunosorbent assay (ELISA). The expression and relative levels of cystatin C mRNA were assessed by in situ hybridization and quantitative real‐time polymerase chain reaction (QRT‐PCR). RESULTS The intensity of cystatin C immunostaining in Gleason grade 2 and 3 prostate cancer was significantly higher than in benign prostatic tissues, but decreased significantly with increasing Gleason grades. There was strong expression of cystatin C in neuroendocrine‐like cells, which increased significantly with increasing Gleason grades. The Ki‐67 immunoreactivity also increased significantly during de‐differentiation. In situ hybridization showed staining patterns in concordance with the immunohistochemical results. ELISA showed high concentrations of cystatin C in benign and malignant tissue extracts and QRT‐PCR further corroborated that the cystatin C gene is highly expressed in both benign and malignant prostatic tissues. CONCLUSIONS There was a significant decrease in the immunohistochemical expression of cystatin C in non‐neuroendocrine prostate cancer cells, concomitant with increasing Gleason grades. That there were more strongly cystatin C‐positive neuroendocrine‐like cells in prostate cancer than in benign prostatic tissue suggests a connection between cystatin C and neuroendocrine differentiation in prostate cancer progression.