Immunocytochemical expression of p16(INK4A) and Ki-67 in cytologically negative and equivocal Pap smears positive for oncogenic human papillomavirus

Immunocytochemical expression of p16(INK4A) and Ki-67 in cytologically negative and equivocal Pap smears positive for oncogenic human papillomavirus

Author Longatto, A. Google Scholar
Utagawa, M. L. Google Scholar
Shirata, N. K. Google Scholar
Pereira, SMM Google Scholar
Namiyama, G. M. Google Scholar
Kanamura, C. T. Google Scholar
Santos, G. D. Google Scholar
Oliveira, M. A. de Google Scholar
Wakamatsu, A. Google Scholar
Nonogaki, S. Google Scholar
Roteli-Martins, C. Google Scholar
di Loreto, C. Google Scholar
Ferraz, MDMD Google Scholar
Maeda, MYS Google Scholar
Alves, VAF Google Scholar
Syrjanen, K. Google Scholar
Institution Adolfo Lutz Inst
Univ Minho
Universidade Federal de São Paulo (UNIFESP)
Leonor Mendes Barros Hosp
Universidade de São Paulo (USP)
Turku Univ
Abstract This study was designed to analyze the cross-sectional comparison of the p16(INK4A) and Ki-67 immunocytochemical expression in negative and equivocal (atypical squamous cells of undetermined significance (ASC-US)) liquid-based cytology (LBQ samples testing positive for high-risk human papillomavirus (HPV) types with HC2 assay or polymerase-chain reaction (PCR). A series of 199 consecutive LBC specimens 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 11 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 negative cytologic samples, 101 were HPV-positive and 55 HPV-negative. of the HPV-positive group, 59 of 101 cases (58.4%) were positive for both p16 and M67 inummostaining, 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 simultaneous positive immunoreaction for p 16 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 between the graded p16 and Ki-67 expression (p = 0.065 for linear trend). in the HPV-negative ASGUS group, there was no statistical association between the graded p16 and Ki-67 positivity (Pearson, p = 0.28 1). 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 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 management of women with equivocal cytology.
Keywords p16
cervical cancer
human papillomavirus
liquid-based cytology
Language English
Date 2005-04-01
Published in International Journal of Gynecological Pathology. Philadelphia: Lippincott Williams & Wilkins, v. 24, n. 2, p. 118-124, 2005.
ISSN 0277-1691 (Sherpa/Romeo, impact factor)
Publisher Lippincott Williams & Wilkins
Extent 118-124
Access rights Closed access
Type Article
Web of Science ID WOS:000227883400002

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