Please use this identifier to cite or link to this item:

TitleImmunocytochemical expression of p16 INK4A and Ki-67 in cytologically negative and equivocal pap smears positive for oncogenic human papillomavirus
Author(s)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.
Cervical cancer
Liquid-based cytology
Human papillomavirus
Issue dateApr-2005
PublisherLippincott, Williams & Wilkins
JournalInternational Journal of Gynecological Pathology
Citation"International Journal of Gynecological Pathology". ISSN 0277-1691. 24:2 (2005) 118-124.
Abstract(s)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.
Publisher version;jsessionid=DP4YnvhMuhHij2gsWP9dHQE34PJtYdGtZ1plfZ9R7WatK1rIqA3M!-786779307!-949856145!9001!-1
AccessOpen access
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

Files in This Item:
File Description SizeFormat 
Longato3.pdf233,79 kBAdobe PDFView/Open

Partilhe no FacebookPartilhe no TwitterPartilhe no DeliciousPartilhe no LinkedInPartilhe no DiggAdicionar ao Google BookmarksPartilhe no MySpacePartilhe no Orkut
Exporte no formato BibTex mendeley Exporte no formato Endnote Adicione ao seu ORCID