Prognostication of Vulvar Cancer Based on p14^sup ARF^ Status: Molecular Assessment of Transcript and Protein

This study was designed to determine the prognostic role of p14^sup ARF^ in vulvar squamous cell carcinoma (VSCC). Immunohistochemistry for p14^sup ARF^ and p53 and fluorescent in situ hybridization (FISH) for TP53 were performed in 139 cases of VSCC. Human papillomavirus (HPV) genotyping by hybridization was employed in 100 cases. qRT-PCR for p14^sup ARF^ and p53 transcript assessment was performed in 16 cases. All results were correlated with clinicopathological variables. Immunohistochemistry analysis showed p14^sup ARF^ and p53 positivity in 16.4 % and 53 % cases respectively. Positive p14^sup ARF^ expression was significantly associated with the following variables: shorter cancer-specific survival (P = 0.04) and shorter disease-free survival (P = 0.02), presence of perineural invasion (P = 0.037), vascular invasion (P = 0.047), and node metastasis (P = 0.031). Also, p14^sup ARF^-positive HPV-negative cases had the shortest cancer-specific survival (P = 0.03) and disease-free survival (P = 0.04). HPV infection was detected in 32.8 % of the cases; HPV16 was the most prevalent type. Viral infection was more common in poorly differentiated tumors (P = 0.032). qRT-PCR demonstrated that CDKN2A (p14^sup ARF^) had higher expression in tumor samples compared with paired noncancerous samples (P < 0.001). The opposite relationship was seen in TP53 expression evaluation (P < 0.001). FISH demonstrated 4 cases with deleted TP53 (6.3 %). p14^sup ARF^ represents an important marker of poor prognosis in VSCC. p53 and HPV infection did not show any prognostic importance. Further clinical trials concerning p14^sup ARF^ positivity may result in important contributions due to its relationship with poor outcome. Mainly due to the relationship of p14^sup ARF^ with lymph node metastasis, the immunohistochemistry evaluation of this marker may help to identify a subset of patients more suitable to less radical procedures.[PUBLICATION ABSTRACT]