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Title: Prognostication of Vulvar Cancer Based on p14(ARF) Status: Molecular Assessment of Transcript and Protein
Authors: LAVORATO-ROCHA, Andre MouraoMAIA, Beatriz de MeloRODRIGUES, Iara Sant'anaSTIEPCICH, Monica Maria AgataBAIOCCHI, GlaucoCESTARI, Flavia Munhoz da SilvaCARVALHO, Katia CandidoSOARES, Fernando AugustoROCHA, Rafael Malagoli
Citation: ANNALS OF SURGICAL ONCOLOGY, v.20, n.1, p.31-39, 2013
Abstract: This study was designed to determine the prognostic role of p14(ARF) in vulvar squamous cell carcinoma (VSCC). Immunohistochemistry for p14(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(ARF) and p53 transcript assessment was performed in 16 cases. All results were correlated with clinicopathological variables. Immunohistochemistry analysis showed p14(ARF) and p53 positivity in 16.4 % and 53 % cases respectively. Positive p14(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(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(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(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(ARF) positivity may result in important contributions due to its relationship with poor outcome. Mainly due to the relationship of p14(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.
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Artigos e Materiais de Revistas Científicas - LIM/58
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular

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