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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 1/2013

01-01-2013 | Healthcare Policy and Outcomes

Prognostication of Vulvar Cancer Based on p14ARF Status: Molecular Assessment of Transcript and Protein

Authors: André Mourão Lavorato-Rocha, MSc, Beatriz de Melo Maia, MSc, Iara Sant’ana Rodrigues, MSc, Mônica Maria Ágata Stiepcich, MD, PhD, Glauco Baiocchi, MD, MSc, PhD, Flávia Munhoz da Silva Cestari, MD, Kátia Cândido Carvalho, MSc, PhD, Fernando Augusto Soares, MD, MSc, PhD, Rafael Malagoli Rocha, MSc, PhD

Published in: Annals of Surgical Oncology | Issue 1/2013

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Abstract

Purpose

This study was designed to determine the prognostic role of p14ARF in vulvar squamous cell carcinoma (VSCC).

Methods

Immunohistochemistry for p14ARF 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 p14ARF and p53 transcript assessment was performed in 16 cases. All results were correlated with clinicopathological variables.

Results

Immunohistochemistry analysis showed p14ARF and p53 positivity in 16.4 % and 53 % cases respectively. Positive p14ARF 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, p14ARF-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 (p14ARF) 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 %).

Conclusions

p14ARF represents an important marker of poor prognosis in VSCC. p53 and HPV infection did not show any prognostic importance. Further clinical trials concerning p14ARF positivity may result in important contributions due to its relationship with poor outcome. Mainly due to the relationship of p14ARF 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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Metadata
Title
Prognostication of Vulvar Cancer Based on p14ARF Status: Molecular Assessment of Transcript and Protein
Authors
André Mourão Lavorato-Rocha, MSc
Beatriz de Melo Maia, MSc
Iara Sant’ana Rodrigues, MSc
Mônica Maria Ágata Stiepcich, MD, PhD
Glauco Baiocchi, MD, MSc, PhD
Flávia Munhoz da Silva Cestari, MD
Kátia Cândido Carvalho, MSc, PhD
Fernando Augusto Soares, MD, MSc, PhD
Rafael Malagoli Rocha, MSc, PhD
Publication date
01-01-2013
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 1/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2560-7

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