Immunohistochemical detection of p16INK4a in liquid-based cytology specimens on cell block sections.
BACKGROUND
Colposcopy biopsy procedure is a standard recommendation for atypical squamous cell cannot exclude high-grade lesion (ASC-H) in abnormal Papanicolaou smears. p16 (p16INK4a), a cell cycle regulator, has been shown to be overexpressed in squamous dysplasia. To further improve the diagnostic accuracy of the ASC-H Papanicolaou smear and to reduce unnecessary procedures, the authors evaluated the utility of immunodetection of p16 in liquid-based cytology specimens on cell blocks.


METHODS
Seventy-five liquid-based (SurePath; TriPath Imaging, Inc. Burlington, NC) cytology specimens were prepared for cell blocks. Three groups (G1, G2, and G3) of cases were included: G1 comprised 44 cases of ASC-H; G2, 14 cases of high-grade dysplasia; and G3, 17 negative/reactive cases. All cases in G1 were confirmed by cervical biopsy or Digene Hybrid Capture 2 (Digene, Gaithersburg, Md) human papilloma virus (HPV) testing. Immunodetection for p16 was performed on cell blocks.


RESULTS
In G1, 26 of 44 (59%) cases showed squamous dysplasia, with 14 high-grade squamous intraepithelial lesion (HSIL) cases. Twenty-two of 28 (79%) p16-positive cases were confirmed by surgical biopsy or HPV testing, with a diagnostic sensitivity of 85%, specificity of 67%, positive predictive value (PPV) of 79%, and negative predictive value (NPV) of 75%. Four cases with false-negative staining for p16 were identified. All 28 cases of HSIL (14 from G1 and 14 from G2) were positive for p16.


CONCLUSIONS
1) p16 is a sensitive marker to confirm the diagnosis of ASC-H on a cell block; 2) Multiple unstained slides with adequate cellularity can be obtained from each cell block; and 3) Additional markers can be used to further increase diagnostic sensitivity and specificity.
Liu
Haiyan
H
Department of Pathology, Lehigh Valley Hospital, Allentown, Pennsylvania, USA.
Shi
Jianhui
J
Wilkerson
Myra
M
Huang
Yajue
Y
Meschter
Steven
S
Dupree
William
W
Lin
Fan
F
D014408:Biomarkers, Tumor / Q000032:analysis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D003584:Cytological Techniques; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018307:Neoplasms, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism; D065006:Papanicolaou Test; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000378:metabolism; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000378:metabolism
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16