Results
Immunohistochemistry
Ki-67 expression was positive in 57/148 (38.5%) of PSCCs. The mean expression was 42% and similar to median value (40%). Different subtypes of PSCC showed significant difference in Ki-67 expression (p<0.0001, figure 1) with highest positivity in basaloid, 16/17 (94.1%) and a lack of Ki-67 positive cases within verrucous tumours, 0/15 (Table 1). Ki-67 protein strongly positively correlated with tumour grade (p<0.0001) but not with stage (p=0.2193) or LNM (p=0.7366). Positive lymph node status at the time of surgery significantly correlated with tumour grade (p=0.0001) and stage (p=0.009).
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Figure 1.
Pattern of Ki-67-positive immunoexpression in subtypes of penile squamous cell carcinoma (PSCC). (A) Basaloid PSCC. (B) Usual type PSCC. (C) Verrucous PSCC. Magnification ×200.
HPV Genotyping
HPV DNA was detected in 57/102 (56%) of PSCCs. High-risk type 16 was the most prevalent type, present in 46/57 (81%) of HPV-positive tumours. Differences in the HPV infections were observed between the histological subtypes of PSCC. HPV DNA was detected in 38/64 (59%) of usual-type tumours, 10/13 (77%) of basaloid and only 3/13 (23%) of verrucous tumours. High-risk HPV strongly correlated with Ki-67 immunoexpression (p<0.0001, Table 2).
Survival Analysis
Follow-up data was available for 134 patients. The prognostic value of Ki-67, as a biomarker for penile cancer-specific survival (CSS) and overall survival (OS), was assessed as a dichotomous variable with a cut-off at 40%. There was no significant difference in OS (p=0.5538) and CSS (p=0.6221, figure 2) for patients with positive and negative Ki-67 expression. In univariate analysis, Ki-67 showed no prognostic value for CSS (HR=1.00, 95%, CI 0.99 to 1.02, p=0.54) or OS (HR=1.00, 95%, CI 0.99 to 1.02, p=0.45). In univariate and multivariate analysis high tumour stage and grade, LNM and age at diagnosis were all prognostic variables for CSS (Table 3) and OS.
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Figure 2.
Cancer-specific survival. Censoring at time-to-last follow-up (log rank test p=0.6221).