title: Loss of claudins-1 and -7 and expression of claudins-3 and -4 correlate with prognostic variables in prostatic adenocarcinomas.
abstract: Claudins, members of a large family of adherent junction proteins, regulate the integrity and function of tight junctions and influence tumorigenesis. Recent studies have shown that altered levels of the different claudins may be related to invasion and progression of carcinoma cells in several primary neoplasms. However, there is no reported study documenting the pattern of claudin expression in prostatic adenocarcinomas (PACs). Formalin-fixed paraffin-embedded sections from 141 PACs were immunostained by manual and automated methods on the Xmatrx (BioGenex, San Ramon, CA) using antihuman claudin-1, -3, -4, -5, and -7 antibodies (Zymed, San Francisco, CA). Membranous immunoreactivity for each protein was semiquantitatively scored in both the tumor and adjacent benign epithelium in each case. Results were correlated with clinicopathologic variables. Variable membranous positivity was noted in the adjacent benign glands for all 5 proteins in all cases. PACs showed variable membranous positivity ranging from decreased, similar to, and increased in relation to the adjacent benign epithelium for all claudins. Decreased expression of claudin-1 correlated with high tumor grade (P = .001) and biochemical disease recurrence (P = .01), whereas decreased claudin-7 correlated with high tumor grade (P < .0001). In contrast, expression of claudin-3 correlated with advanced stage tumors (P = .03) and recurrence (P = .02), and expression of claudin-4 correlated with advanced stage (P = .02). On multivariate analysis, advanced stage (P = .026) and decreased claudin-1 protein expression (P = .005) independently predicted disease recurrence. Immunohistochemical expression and prognostic significance of claudins are variable in PACs, with decreased expression of claudin-1 emerging as an independent prognostic variable warranting further study.
authors.affiliation: Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY 12208, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Sheehan
authors.forename: Bhaskar V S
authors.initials: BV
authors.lastname: Kallakury
authors.forename: Christine E
authors.initials: CE
authors.lastname: Sheehan
authors.forename: Hugh A G
authors.initials: HA
authors.lastname: Fisher
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Kaufman
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019108:Tight Junctions / Q000378:metabolism
chemical_list: C568108:CLDN1 protein, human; C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; C473255:CLDN7 protein, human; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D008565:Membrane Proteins