Vulvar intraepithelial neoplasia p53 expression, p53 gene mutation and HPV in recurrent/progressive cases.
OBJECTIVE
To evaluate p53 protein overexpression and p53 gene mutation in primary and recurrent undifferentiated vulvar intraepithelial neoplasia (VIN), establishing the recurrence and progression rates, median time interval, and sites of the initial lesion and first recurrence, addressing the relationship with HPV infection.


METHODS
Twenty women with undifferentiated VIN treated with wide surgical excision were followed every 6 months for 7 years and divided into groups with and without recurrence/progression. p53 Protein was detected in paraffin sections using the monoclonal p53 antibody. DNA was extracted from paraffin sections. Polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) analysis was utilized to screen for p53 gene mutations in exons 5-8. HPV was determined by digesting PCR products with restriction endonucleases.


RESULTS
Recurrences were observed in 8 (40%) patients and progression to cancer in 1 (5%). Two cases recurred twice. The median interval for recurrence/progression was 24.5 months. Recurrent/progressive lesions were located in the same area of the initial lesions in 10 cases (91%). p53 Overexpression was observed in 50% (10/20) of primary lesions, of which 45% corresponded to the 9 recurrent/progressive cases. p53 Overexpression was detected in 81.8% (9/11) of recurrent/progressive cases. In the last 2 cases PCR-SSCP showed p53 gene mutation. The rate of HPV infection was higher in the group without recurrence.


CONCLUSIONS
p53 Gene mutation plays an important role in undifferentiated VIN pathogenesis independent of high-risk HPV infection and may predict recurrence or progression to vulvar cancer. Undifferentiated VIN recurrent/progressive VIN lesions have a tendency to occur in the same area of the initial lesions, suggesting a molecular disturbance.
Chulvis do Val
Isabel C
IC
Vulvar Pathology Unit, Institute of Gynecology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. isabeldoval@uol.com.br
Almeida Filho
Gutemberg L
GL
Valiante
Paulo M
PM
Gondim
Consuelo
C
Takiya
Christina M
CM
Carvalho
Maria da Gloria da C
Mda G
D000328:Adult; D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D016158:Genes, p53; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D009364:Neoplasm Recurrence, Local; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014846:Vulvar Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53