Dual-Stain for P16 and Ki-67 in the Interpretation of Abnormal PAP Cytology Results: A Prospective Study
M Chivukula, RM Austin, A Duwe, T Friedman, J Masko, N Mauser, R Ridder. Magee Women's Hospital of UPMC, Pittsburgh, PA; MTM Labortatories, Hiedelberg, Germany
Background: p16 has been found to be strongly over-expressed in nearly all high-grade pre-cancerous and cancerous cervical lesions and may serve as a surrogate marker for the transforming activity of high-risk HPV. As over-expression of the cell-cycle regulatory protein p16 in cells with intact cell cycle regulation should prevent those cells from proliferating, we further tested the hypothesis that the detection of individual cells simultaneously co-expressing p16 protein and proliferation marker Ki-67 can be used as an indicator for the presence of cervical dysplasia. To accomplish this goal we initiated a large prospective study on cervical cytology specimens showing Pap abnormalities.
Design: Residual materials from liquid-based cytology specimens of women attending cervical cancer screening at a major tertiary hospital and reference center over one year period were used for the analysis. Specimens with any abnormal Pap cytology result (ASC-US+) were included. For each case, an additional ThinPrep™ slide was prepared and immuno-stained using a prototypic dual staining reagent kit (CINtec®Cytology, Dual stain) for the simultaneous detection of p16 and Ki-67 expression on the same slide. The presence of one or more individual cells co-expressing both p16 and Ki-67 were interpreted as “positive” test result. Follow-up biopsy and HPV results were obtained.
Results: Sensitivity of the Dual stain was 87.0% for CIN2+ and 95.7% for CIN3+, with specificity of 89.8% for non high-grade CIN. In ASC-US/ASC-H/LSIL categories with positive HPV results, a positive Dual stain result identified all CIN3+ cases at high levels of specificity (up to 80%).
Conclusions: Initial results from a first set of cytology specimens subjected to simultaneous p16/Ki-67 dual staining and with biopsy follow-up (n=661) indicate both high sensitivity and specificity of this novel screening approach to detection of CIN2/3+ on biopsy follow-up. Results showing high specificity rates for the Dual stain support this approach as an enhancement for detecting histopathological CIN2/3+.
Tuesday, March 23, 2010 11:15 AM
Platform Session: Section F, Tuesday Morning