Calcium-binding proteins S100A8 and S100A9 as novel diagnostic markers in human prostate cancer.
OBJECTIVE
S100 proteins comprise a family of calcium-modulated proteins that have recently been associated with epithelial tumors. We examined the expression of two members of this family, S100A8 and S100A9, together with the S100 receptor RAGE (receptor for advanced glycation end products) in human prostate adenocarcinomas and in prostatic intraepithelial neoplasia.


METHODS
Tissue specimens of 75 patients with organ-confined prostate cancer of different grades were analyzed by immunohistochemistry for expression of S100A8, S100A9, and RAGE. In addition, in situ hybridization of S100A8 and S100A9 was done for 20 cases. An ELISA was applied to determine serum concentrations of S100A9 in cancer patients compared with healthy controls or to patients with benign prostatic hyperplasia (BPH).


RESULTS
S100A8, S100A9, and RAGE were up-regulated in prostatic intraepithelial neoplasia and preferentially in high-grade adenocarcinomas, whereas benign tissue was negative or showed weak expression of the proteins. There was a high degree of overlap of S100A8 and S100A9 expression patterns and of S100A8 or S100A9 and RAGE, respectively. Frequently, a gradient within the tumor tissue with an increased expression toward the invaded stroma of the prostate was observed. S100A9 serum levels were significantly elevated in cancer patients compared with BPH patients or healthy individuals.


CONCLUSIONS
Our data suggest that enhanced expression of S100A8, S100A9, and RAGE is an early event in prostate tumorigenesis and may contribute to development and progression or extension of prostate carcinomas. Furthermore, S100A9 in serum may serve as useful marker to discriminate between prostate cancer and BPH.
Hermani
Alexander
A
Research Group Hormones and Signal Transduction, German Cancer Research Center, Heidelberg, Germany.
Hess
Jochen
J
De Servi
Barbara
B
Medunjanin
Senad
S
Grobholz
Rainer
R
Trojan
Lutz
L
Angel
Peter
P
Mayer
Doris
D
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000097:blood; D040501:Calgranulin A / Q000096:biosynthesis* / Q000097:blood; D040502:Calgranulin B / Q000096:biosynthesis* / Q000097:blood; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D017127:Glycation End Products, Advanced; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D019048:Prostatic Intraepithelial Neoplasia / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000097:blood; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D040501:Calgranulin A; D040502:Calgranulin B; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic