Autor(es):
Longatto Filho, Adhemar 
; Utagawa, Maria Lúcia ; Shirata, Neuza Kasumi ; Pereira, Sónia Maria Miranda ; Namiyama, Gislene ; Kanamura, Cristina Takami ; Santos, Gilda da Cunha ; Oliveira, Marilene Almeida de ; Wakamatsu, Alda ; Nonogaki, Suely ; Roteli-Martins, C. ; Loreto, Celso di ; Ferraz, Maria da Gloria Mattosinho de Castro ; Syrjänen, K.
Data: 2005
Identificador Persistente: http://hdl.handle.net/1822/4037
Origem: RepositóriUM - Universidade do Minho
Assunto(s): p16; Cervical cancer; Ki67; Liquid-based cytology; Human papillomavirus
Descrição
This study was designed to analyze the cross-sectional comparison of the
p16
INK4A
and Ki-67 immunocytochemical expression in negative and equivocal (atyp-ical
squamous cells of undetermined significance (ASC-US)) liquid-based cytology
(LBC) samples testing positive for high-risk human papillomavirus (HPV) types with
HC2 assay or polymerase-chain reaction (PCR). A series of 199 consecutive LBC speci-mens
derived from the same number of women participating in the ongoing Latin American
Screening Study at Leonor Mendes de Barros Hospital, São Paulo, were analyzed
using immunocytochemistry for expression of p16
INK4A
and Ki-67 in negative and
equivocal LBC samples testing positive for high-risk HPV types with hybrid capture
II test (HC2) or PCR. All patients with at least one test positive (cytology, PCR, and/or
HC2) were followed each 6 months for 3 years. The follow-up procedure consisted of
visual examination, colposcopic inspection, cytology, and HC2 assay. Among the neg-ative
cytologic samples, 101 were HPV-positive and 55 HPV-negative. Of the HPV-pos-itive
group, 59 of 101 cases (58.4%) were positive for both p16 and Ki67
immunostaining, and 17 of 101 (16.8%) were negative for both. The proportion of
Ki-67-positivity increased almost in parallel with the increasing grade of p16-positivity
(p = 0.0001 for linear trend). In the HPV-negative group, both markers were negative in
41 of 55 cases (74.5%), and no statistical relationship was observed between the two
markers (Pearson, p = 0.595). HPV-positive ASC-US samples demonstrated a simulta-neous
positive immunoreaction for p16 and Ki67 in 11 of 16 cases (68.7%), whereas 3
(18.7%) were concurrently negative. The relationship between the two markers was of
borderline significance (Pearson, p = 0.053), but no linear relationship was found be-tween
the graded p16 and Ki-67 expression (p = 0.065 for linear trend). In the HPV-negative
ASC-US group, there was no statistical association between the graded p16
and Ki-67 positivity (Pearson, p = 0.281). After 36 months of follow-up of the ASC-US
patients, 6 women still displayed ASC-US smear, of which 4 of 6 were HPV-positive
and expressed both p16 and Ki-67 markers. Two of 43 ASC-US smears had high-grade squamous intraepithelial lesions diagnosed (4.6%), and 1 had low-grade squamous
intraepithelial lesion (2.3%). All of those were positive for HPV, p16 and Ki-67. Patients
with ASC-US diagnosis and positive high-risk HPV status and positive for p16
INK4A
Ki67 should be carefully observed to exclude occurrence of a squamous intraepithelial
lesion. The combination of these two markers can be a useful implement for manage-ment
of women with equivocal cytology.
