title: Expression of S100A4 in renal epithelial neoplasms.
abstract: Expression of S100A4 has been associated with progression and poor clinical outcome in a variety of malignancies including those of the breast, pancreas, bladder, and thyroid. To date, the expression of S100A4 protein in renal epithelial neoplasms is poorly understood. In this study, we evaluated the expression of S100A4 protein and mRNA in the nontumoral kidney and renal epithelial neoplasms of different types and correlated its expression with patient outcome. The study population included 155 clear cell renal cell carcinomas (cRCC), 22 papillary renal cell carcinomas (pRCC), 13 chromophobe renal cell carcinomas and 13 oncocytomas. In nontumoral kidney, nuclear and cytoplasmic S100A4 staining was detected in the glomerular epithelium and endothelium, distal tubules and collecting ducts, and loops of Henle. A different expression pattern was noted in the various neoplasms. S100A4 expression was significantly increased in the stromal cells in cRCC (83%) and pRCC (73%) compared with paired nontumoral kidney tissue (P<0.001). There was no increased stromal cell expression of S100A4 in oncocytomas and chromophobe carcinomas. Positive epithelial staining was more common in pRCC (58%) than cRCC (11%) (P=0.01). The level of mRNA detected by reverse transcription-polymerase chain reaction was significantly higher in the tumor as opposed to normal tissue in cRCC but not in the other neoplasms (P=0.03). Multivariate analysis revealed that epithelial S100A4 protein expression is an independent poor prognostic factor along with grade and stage only in cRCC (P<0.01). Although S100A4 protein was expressed in a minority of cRCC, its expression was associated with shorter overall patient survival.
authors.affiliation: Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Li J
authors.initials: LJ
authors.lastname: Wang
authors.forename: Andres
authors.initials: A
authors.lastname: Matoso
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Sciandra
authors.forename: Evgeny
authors.initials: E
authors.lastname: Yakirevich
authors.forename: Edmond
authors.initials: E
authors.lastname: Sabo
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Meitner
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Tavares
authors.forename: Lelia
authors.initials: L
authors.lastname: Noble
authors.forename: Gyan
authors.initials: G
authors.lastname: Pareek
authors.forename: Ronald A
authors.initials: RA
authors.lastname: DeLellis
authors.forename: Murray B
authors.initials: MB
authors.lastname: Resnick
mesh_terms: D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012189:Retrospective Studies; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis*; D015996:Survival Rate
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human