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 p16INK4a, 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 p16INK4a in 88% cases and p53 in 35% of cases, whereas HR-HPV- PSCCs were positive for p16INK4a 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.
Written by:
Barzon L, Cappellesso R, Peta E, Militello V, Sinigaglia A, Fassan M, Simonato F, Guzzardo V, Ventura L, Blandamura S, Gardiman M, Palù G, Fassina A. Are you the author?
Department of Molecular Medicine, University of Padua, Padua, Italy; Department of Medicine, University of Padua, Padua, Italy; Virology Unit, Parma University Hospital, Parma, Italy; Veneto Region Oncology Institute (Istituto Oncologico Veneto-IRCCS), Padua, Italy; Department of Statistical Sciences, University of Padua, Padua, Italy.
Reference: Am J Pathol. 2014 Dec;184(12):3376-83.
doi: 10.1016/j.ajpath.2014.08.004
PubMed Abstract
PMID: 25455689