Chromosomal Aberrations

Whole genome studies on penile cancer are scarce. DNA ploidy studies suggest the frequency of DNA aneuploidy to be correlated with histological type of invasive squamous cell carcinoma of the penis37,38 and patients with DNA diploid cancer to have a better survival rate than patients with aneuploid cancer.39 Preliminary analysis suggests that patients with a high DNA index may be at increased risk of disease progression and metastatic involvement.38,40 Karyotype analysis has been reported in a very small set of penile cancers (n = 4), of which three of the four presented with a variety of cytogenetic anomalies.41-43 The tumors with cytogenetic abnormalities seem to have a more aggressive component, though clearly further data linking chromosomal abnormalities to biological behavior and outcome are necessary to state this firmly. In a comparative genomic hybridization study of 26 cases,44 DNA copy number alterations were present in 23 cases (89%). The CGH analysis using metaphase spreads showed aberrations in all chromosomes, at varying frequencies. The most common copy number gains were found in 8q24, 16p11-12, 20q11-13, 22q, 19q13, and 5p15, and the most common deletions were detected in 13q21-22, 4q21-32, and along the X chromosome. These alterations were similar to those detected in other SCC types, such as oral and esophageal SCC. No clear correlation between tumor grade and chromosome aberrations could be detected, but there was a tendency for lower copy number alterations being associated with shorter survival times. It would be worthwhile to extend these CGH studies and combine chromosomal patterns of various HPV-positive versus negative cancers, including those of other anatomical sites such as vulva and oropharynx, to determine both unique patterns and common denominators in HPV-mediated and HPV-unrelated carcinogenesis.

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