title: Validation of 34betaE12 immunoexpression in clear cell papillary renal cell carcinoma as a sensitive biomarker.
abstract: Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognised neoplasm with a broad spectrum of morphological characteristics, thus representing a challenging differential diagnosis, especially with the low malignant potential multicystic renal cell neoplasms and clear cell renal cell carcinoma. We selected 14 cases of CCPRCC with a wide spectrum of morphological features diagnosed on morphology and CK7 immunoreactivity and analysed them using a panel of immunohistochemical markers, focusing on 34βE12 and related CKs 1,5,10 and 14 and several molecular analyses such as fluorescence in situ hybridisation (FISH), array comparative genomic hybridisation (aCGH), VHL methylation, VHL and TCEB1 sequencing and multiplex ligation-dependent probe amplification (MLPA). Twelve of 13 (92%) CCPRCC tumours were positive for 34βE12. One tumour without 3p alteration by FISH revealed VHL mutation and 3p deletion at aCGH; thus, it was re-classified as clear cell RCC. We concluded that: (1) immunohistochemical expression of CK7 is necessary for diagnostic purposes, but may not be sufficient to identify CCPRCC, while 34βE12, in part due to the presence of CK14 antigen expression, can be extremely useful for the recognition of this tumour; and (2) further molecular analysis of chromosome 3p should be considered to support of CCPRCC diagnosis, when FISH analysis does not evidence the common loss of chromosome 3p.
authors.affiliation: Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust of Verona, Verona, Italy; Pederzoli Hospital, Anatomic Pathology, Peschiera del Garda, Verona, Italy. Electronic address: guido.martignoni@univr.it.
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.affiliation: Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.affiliation: Pederzoli Hospital, Anatomic Pathology, Peschiera del Garda, Verona, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Segala
authors.affiliation: Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Munari
authors.affiliation: Pederzoli Hospital, Anatomic Pathology, Peschiera del Garda, Verona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gobbo
authors.affiliation: Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Cima
authors.affiliation: Hartmann Institute and HUSLab, University of Helsinki, Department of Pathology, Helsinki, Finland.
authors.forename: Ioana
authors.initials: I
authors.lastname: Borze
authors.affiliation: Hartmann Institute and HUSLab, University of Helsinki, Department of Pathology, Helsinki, Finland.
authors.forename: Tina
authors.initials: T
authors.lastname: Wirtanen
authors.affiliation: Hartmann Institute and HUSLab, University of Helsinki, Department of Pathology, Helsinki, Finland.
authors.forename: Virinder Kaur
authors.initials: VK
authors.lastname: Sarhadi
authors.affiliation: MRC-Holland, Amsterdam, Netherlands.
authors.forename: Lilit
authors.initials: L
authors.lastname: Atanesyan
authors.affiliation: MRC-Holland, Amsterdam, Netherlands.
authors.forename: Suvi
authors.initials: S
authors.lastname: Savola
authors.affiliation: Histology, Microbiology and Medical Biotechnologies, University of Padua, Padua, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Barzon
authors.affiliation: Histology, Microbiology and Medical Biotechnologies, University of Padua, Padua, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Masi
authors.affiliation: Department of Pathology, Anatomic Pathology, University of Padua, Padua, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States.
authors.forename: John N
authors.initials: JN
authors.lastname: Eble
authors.affiliation: Hartmann Institute and HUSLab, University of Helsinki, Department of Pathology, Helsinki, Finland.
authors.forename: Tom
authors.initials: T
authors.lastname: Bohling
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Wellington School of Medicine and Health Sciences, Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand.
authors.forename: Brett
authors.initials: B
authors.lastname: Delahunt
authors.affiliation: Hartmann Institute and HUSLab, University of Helsinki, Department of Pathology, Helsinki, Finland.
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor
keywords: 34βE12; CK14 antigen expression; CK7 immunoreactivity; Clear cell papillary renal cell carcinoma; FISH analysis; VHL mutation; aCGH; biomarker; chromosome 3p deletion