title: Profiling of expression of human papillomavirus-related cancer miRNAs in penile squamous cell carcinomas.
abstract: Penile squamous cell carcinoma (PSCC) is a rare tumor associated with high-risk human papillomavirus (HR-HPV) infection in 30% to 60% of cases. Altered expression of miRNAs has been reported in HPV-related cervical and head and neck cancers, but such data have not been available for PSCC. We analyzed a series of 59 PSCCs and 8 condylomata for presence of HPV infection, for p16(INK4a), Ki-67, and p53 immunohistochemical expression, and for expression of a panel of cellular miRNAs (let-7c, miR-23b, miR-34a, miR-145, miR-146a, miR-196a, and miR-218) involved in HPV-related cancer. HR-HPV DNA (HPV16 in most cases) was detected in 17/59 (29%) PSCCs; all penile condylomata (8/8) were positive for low-risk HPV6 or HPV11. HR-HPV(+) PSCCs overexpressed p16(INK4a) in 88% cases and p53 in 35% of cases, whereas HR-HPV(-) PSCCs were positive for p16(INK4a) and p53 immunostaining in 9% and 44% of cases, respectively. Among the miRNAs investigated, expression of miR-218 was lower in PSCCs with HR-HPV infection and in p53(-) cancers. Hypermethylation of the promoter of the SLIT2 gene, which contains miR-218-1 in its intronic region, was frequently observed in PSCCs, mainly in those with low miR-218 expression. Epigenetic silencing of miR-218 is a common feature in HR-HPV(+) PSCCs and in HR-HPV(-) PSCCs without immunohistochemical detection of p53.
authors.affiliation: Department of Molecular Medicine, University of Padua, Padua, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Barzon
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Cappellesso
authors.affiliation: Department of Molecular Medicine, University of Padua, Padua, Italy.
authors.forename: Elektra
authors.initials: E
authors.lastname: Peta
authors.affiliation: Department of Molecular Medicine, University of Padua, Padua, Italy; Virology Unit, Parma University Hospital, Parma, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Militello
authors.affiliation: Department of Molecular Medicine, University of Padua, Padua, Italy; Veneto Region Oncology Institute (Istituto Oncologico Veneto-IRCCS), Padua, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sinigaglia
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonato
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Guzzardo
authors.affiliation: Department of Statistical Sciences, University of Padua, Padua, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ventura
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Stella
authors.initials: S
authors.lastname: Blandamura
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Gardiman
authors.affiliation: Department of Molecular Medicine, University of Padua, Padua, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy. Electronic address: ambrogio.fassina@unipd.it.
authors.forename: Ambrogio
authors.initials: A
authors.lastname: Fassina
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000378:metabolism* / Q000821:virology*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications; D010412:Penile Neoplasms / Q000150:complications / Q000378:metabolism* / Q000821:virology*; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C498990:SLIT3 protein, human; D000098552:Slit Homolog 2 Protein