title: Immunohistochemical analysis of Reg IV in urogenital organs: Frequent expression of Reg IV in prostate cancer and potential utility as serum tumor marker.
abstract: Regenerating islet-derived family, member 4 (Reg IV) is a candidate marker for cancer and inflammatory bowel disease and is associated with neuroendocrine and intestinal differentiation. We have reported that 14% of prostate cancer (PCa) cases are positive for Reg IV by immunohistochemistry. In the present study, we performed immunohistochemical analysis of Reg IV in other major urological cancers, including 101 renal cell carcinoma (RCC), and 95 urothelial carcinoma (UC) of urinary bladder by immunohistochemistry. We also investigated neuroendocrine differentiation by chromogranin A and synaptophysin staining along with intestinal differentiation by MUC2 staining. Immunohistochemical analysis of Reg IV revealed no expression of Reg IV in RCC, and only one case (1%) of UC expressed Reg IV. Neither neuroendocrine nor intestinal differentiation was found in RCC. Among 95 UC cases, neuroendocrine differentiation was detected in 13 cases (14%), and intestinal differentiation was observed in 33 cases (35%). In one Reg IV-positive UC case, MUC2 staining was observed. Since Reg IV expression was frequently found in PCa, we also measured Reg IV levels in sera from patients with PCa by enzyme-linked immunosorbent assay. The serum Reg IV concentration in PCa patients (n=38, mean +/- SE, 1.69+/-0.16 ng/ml) was significantly higher than that in control individuals (n=40, 1.28+/-0.11 ng/ml, P=0.0199, Mann-Whitney U test). The sensitivity and specificity for detection of PCa were 34% (13/38) and 90% (36/40), respectively. These results suggest that among major urologic cancers, Reg IV is expressed frequently in PCa, and that serum Reg IV represents a novel biomarker for PCa.
authors.affiliation: Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8551, Japan.
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Hayashi
authors.forename: Akio
authors.initials: A
authors.lastname: Matsubara
authors.forename: Shinya
authors.initials: S
authors.lastname: Ohara
authors.forename: Koji
authors.initials: K
authors.lastname: Mita
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Tsuguru
authors.initials: T
authors.lastname: Usui
authors.forename: Koji
authors.initials: K
authors.lastname: Arihiro
authors.forename: Shinichi
authors.initials: S
authors.lastname: Norimura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sentani
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000097:blood; D053379:Chromogranin A / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000097:blood; D037181:Lectins, C-Type / Q000097:blood*; D008297:Male; D008875:Middle Aged; D055262:Mucin-2 / Q000096:biosynthesis; D000073718:Pancreatitis-Associated Proteins; D011471:Prostatic Neoplasms / Q000097:blood*; D012680:Sensitivity and Specificity; D016708:Synaptophysin / Q000096:biosynthesis; D001749:Urinary Bladder Neoplasms / Q000097:blood; D014565:Urogenital Neoplasms / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D053379:Chromogranin A; D037181:Lectins, C-Type; C524625:MUC2 protein, human; D055262:Mucin-2; D000073718:Pancreatitis-Associated Proteins; C428528:REG4 protein, human; D016708:Synaptophysin