title: Prognostication of vulvar cancer based on p14ARF status: molecular assessment of transcript and protein.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Anatomic Pathology, Cancer Hospital AC Camargo, São Paulo, Brazil. lavorato.andre@gmail.com
authors.forename: André Mourão
authors.initials: AM
authors.lastname: Lavorato-Rocha
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Melo Maia
authors.forename: Iara Sant'ana
authors.initials: IS
authors.lastname: Rodrigues
authors.forename: Mônica Maria Ágata
authors.initials: MM
authors.lastname: Stiepcich
authors.forename: Glauco
authors.initials: G
authors.lastname: Baiocchi
authors.forename: Flávia Munhoz
authors.initials: FM
authors.lastname: da Silva Cestari
authors.forename: Kátia Cândido
authors.initials: KC
authors.lastname: Carvalho
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.forename: Rafael Malagoli
authors.initials: RM
authors.lastname: Rocha
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001808:Blood Vessels / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D052162:Human papillomavirus 16; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D030361:Papillomavirus Infections / Q000150:complications*; D010525:Peripheral Nerves / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014846:Vulvar Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53