Challenging the prognostic impact of the new WHO and TNM classifications with special emphasis on HPV status in penile carcinoma

miRNA expression characterizes histological subtypes and metastasis in penile squamous cell carcinoma

“…It is of high clinical impact to identify patients who are at a high risk of metastasis and are likely to benefit from invasive therapies such as early inguinal lymph node dissection or adjuvant systemic chemotherapy. We and others proved regional lymph node involvement and lymph vessel invasion as independent prognostic factors in PSCC [19][20][21]. However, these parameters are not sufficient for individual therapy selection to improve treatment in high-risk patients and to prevent adverse effects in low-risk patients.…”

“…HPV infection is one of the most common risk factors in PSCC [1]. The prognostic role of HPV, however, is still debated [19,[33][34][35][36]. The current WHO classification of PSCC is now based on clinicopathologic uniqueness and HPV status, and it assigns histological subtypes to HPV-related and non-HPV-related PSCC [5].…”

“…The patient samples were obtained from urology departments in Germany and Russia as described in our previous cohort study [19] (Table 1 and Table S1). Thirty samples, including 22 tumor tissue and 8 normal tissue samples, were used for screening by microarray analysis.…”

“…For validation by PCR, 45 samples (27 tumor and 18 normal tissue samples) were analyzed, including those from the screening cohort. The hematoxylin and eosin (H&E)-stained tissue sections were assessed by two pathologists to confirm histologic subtypes as previously described [19]. Written informed consent was obtained from patients in most cases.…”

“…Total DNA and RNA (including small RNA) were isolated from formalin-fixed, paraffin-embedded (FFPE) tissue sections, prepared by punches from defined tumoraffected or normal areas, using AllPrep ® DNA/RNA FFPE Kits (Qiagen, Hilden Germany) according to the manufacturer's instructions. Detection of HPV infection was performed by HPV polymerase chain reaction (PCR) for GP5+/6+ and Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) primers using the LightCycler ® 1.5 instrument (Roche Diagnostics GmbH) as previously described [19,32]. The concentration and purity of the RNA was assessed using the ratio of absorbance levels at 230, 260, and 280 nm, determined using a NanoDrop™ ND-1000 Spectrophotometer (ThermoFisher Scientific, Dreieich, Germany).…”