Abstract
Penile squamous cell carcinoma is a rare disease, in which somatic genetic aberrations have yet to be characterized. We hypothesized that gene copy aberrations might correlate with human papillomavirus status and clinico-pathological features. We sought to determine the spectrum of gene copy number aberrations in a large series of PSCCs and to define their correlations with human papillomavirus, histopathological subtype, and tumor grade, stage and lymph node status. Seventy formalin-fixed, paraffin embedded penile squamous cell carcinomas were centrally reviewed by expert uropathologists. DNA was extracted from micro-dissected samples, subjected to PCR-based human papillomavirus assessment and genotyping (INNO-LiPA human papillomavirus Genotyping Extra Assay) and microarray-based comparative genomic hybridization using a 32K Bacterial Artificial Chromosome array platform. Sixty-four samples yielded interpretable results. Recurrent gains were observed in chromosomes 1p13.3-q44 (88%), 3p12.3-q29 (86%), 5p15.33-p11 (67%) and 8p12-q24.3 (84%). Amplifications of 5p15.33-p11 and 11p14.1-p12 were found in seven (11%) and four (6%) cases, respectively. Losses were observed in chromosomes 2q33-q37.3 (86%), 3p26.3-q11.1 (83%) and 11q12.2-q25 (81%). Although many losses and gains were similar throughout the cohort, there were small significant differences observed at specific loci, between human papillomavirus positive and negative tumors, between tumor types, and tumor grade and nodal status. These results demonstrate that despite the diversity of genetic aberrations in penile squamous cell carcinomas, there are significant correlations between the clinico-pathological data and the genetic changes that may play a role in disease natural history and progression and highlight potential driver genes, which may feature in molecular pathways for existing therapeutic agents.
Highlights
Penile squamous cell carcinoma (PSCC) is a rare disease, but can have a profound physical and psychological effect on those afflicted
We have provided a detailed characterization of the genetic landscape of prostate cancer by DNA copy number aberrations found in HPV-positive and HPV-negative PSCCs, and demonstrated that these tumors display similar patterns of genetic aberrations despite the distinct pathogenetic mechanisms, with statistically significant changes in only a few small loci
MDM2 and TP53 form an auto-regulatory negative-feedback loop, in which TP53 induces the expression of MDM2, which facilitates the breakdown of TP53 in the nucleus and cytoplasm, inhibits its transcriptional activity and assists its nuclear export [30]
Summary
Penile squamous cell carcinoma (PSCC) is a rare disease, but can have a profound physical and psychological effect on those afflicted. It mainly affects men aged 50–70 years old [1] and, rare in developed countries, it is a significant health problem in developing countries. PSSCs comprise a spectrum of lesions that differ in clinical behavior. The most common morphological subtypes of PSCC are usual type (48–65%), basaloid (4–10%), warty (7–10%) and verrucous (3–8%) [5]. Basaloid carcinomas are the most aggressive PSCC subtype, whereas verrucous carcinomas have a more indolent clinical course [6]
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