title: Silver-enhanced in situ hybridization for detection of polyomavirus DNA in patients with BK virus nephropathy.
abstract: BK virus nephropathy is not an infrequent complication of renal transplantation associated with high rates of graft loss. Although antibodies against SV40 antigen detect different viruses of the polyomavirus family, immunohistochemistry is widely used to confirm the diagnosis of BK virus nephropathy in renal biopsies. Here we aimed to validate the novel silver-enhanced in situ hybridization (SISH) technique for the automated detection of BK virus in renal transplant biopsies. Two different patient cohorts were included. Twenty-nine consecutive patients suspicious for BK virus infection were investigated by SISH and chromogenic in situ hybridization. An additional 26 renal biopsies positive by SV40 immunohistochemistry from 19 patients were analyzed by SISH. Polyomavirus DNA serum levels, as determined by nested PCR analysis, were available for all of these patients. The presence of BK virus DNA in renal tubular cells was identified in 5 of the suspicious cases by both, SISH and chromogenic in situ hybridization . One additional patient was only positive in the SISH. In the second cohort, SISH was positive in all SV40 positive biopsies, but SISH signals were less extensive than SV40 immunohistochemistry. Our results show that the BK virus SISH is an ancillary tool for the detection of polyomavirus DNA in renal biopsies using bright-field microscopy. However, its diagnostic value in comparison with standard immunohistochemistry seems to be limited.
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Florian R
authors.initials: FR
authors.lastname: Fritzsche
authors.forename: Silvio
authors.initials: S
authors.lastname: Pianca
authors.forename: Ariana
authors.initials: A
authors.lastname: Gaspert
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Varga
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Michael P
authors.initials: MP
authors.lastname: Farrell
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Chen
authors.forename: Hans H
authors.initials: HH
authors.lastname: Hirsch
authors.forename: Erik
authors.initials: E
authors.lastname: Springer
authors.forename: Thomas
authors.initials: T
authors.lastname: Fehr
authors.forename: Jonathan
authors.initials: J
authors.lastname: Myles
authors.forename: Raymond
authors.initials: R
authors.lastname: Tubbs
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001331:Automation / Q000379:methods; D001739:BK Virus / Q000235:genetics / Q000302:isolation & purification*; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods*; D007674:Kidney Diseases / Q000175:diagnosis* / Q000821:virology; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D027601:Polyomavirus Infections / Q000175:diagnosis* / Q000821:virology; D012680:Sensitivity and Specificity; D012834:Silver / Q000378:metabolism*; D013194:Staining and Labeling / Q000379:methods*; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D012834:Silver