Morphologic characteristics of p16INK4a-positive cells in cervical cytology samples.
OBJECTIVE
Overexpression of p16INK4a has been proposed as a biomarker helpful for the identification of dysplastic cervical epithelial cells on histologic slides as well as in cervical smears. Since a few nontransformed cells in the genital tract in some instances may also express p16INK4a, we evaluated whether applying established morphologic criteria for cervical dysplasia allows a distinction of dysplastic from nondysplastic p16INK4a-stained cells in cytologic samples.


METHODS
Liquid-based cytology samples were obtained from a screening population (n=50), and from patients attending a dysplasia clinic (n=40). Slides prepared from these samples were stained with the conventional Papanicolaou stain procedure. From each specimen, a second slide was prepared in parallel and immunostained for p16INK4a. Cytologic diagnoses for most patients attending the dysplasia clinic could be compared to the reported histologic diagnoses on punch biopsy samples taken from the patients at the time of colposcopy. This allowed a comparison of the cytology and p16INK4a immunostaining results with subsequent hematoxylin and eosin-based histologic diagnoses.


RESULTS
Overall, in 10% of slides obtained from patients with nonsuspicious smears, few p16INK4a-positive cells were found. Using established morphologic criteria and applying these criteria on cells showing any p16INK4a immunoreactivity, p16INK4a-positive normal or metaplastic cells could be discriminated from p16INK4a-expressing dysplastic cells. In 21 of 22 cases (95%) of high grade lesions (cervical intraepithelial neoplasia 2 or higher in follow-up histology), easily recognizable p16INK4a-positive dysplastic cells could be detected, with the remaining case lacking dysplastic cells in the thin-layer slide used for p16INK4a immunostaining.


CONCLUSIONS
Established morphologic criteria for cervical dysplasia can be readily applied to p16INK4a-immunostained cytologic specimens. Thus, p16INK4a immunostaining may help to avoid ambiguities in the interpretation of cervical cytology samples and facilitate more rapid diagnosis and possibly even automated screening of cytologic slides.
Trunk
Marcus J
MJ
mtm laboratories AG, Heidelberg, Germany.
Dallenbach-Hellweg
Gisela
G
Ridder
Ruediger
R
Petry
Karl Ulrich
KU
Ikenberg
Hans
H
Schneider
Volker
V
von Knebel Doeberitz
Magnus
M
D000368:Aged; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D003951:Diagnostic Errors / Q000517:prevention & control; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008679:Metaplasia / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D065006:Papanicolaou Test; D011237:Predictive Value of Tests; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*; D014626:Vaginal Smears / Q000379:methods*
D019941:Cyclin-Dependent Kinase Inhibitor p16