Immunocytochemistry with p16INK4a (p16) and Ki-67 as Adjuncts to the Pap Test
Edward T Jones, Larry J Fowler, Edward J Wilkinson. University of Florida, Gainesville, FL
Background: Predicting which women with low-grade squamous intraepithelial lesions (LSIL) on cervical Pap tests have or will develop high-grade cervical intraepithelial neoplasia (CIN2+) on cervical biopsy remains problematic due to the poor specificity of the Pap test and the transient nature of most HPV infections. It has been reported that the specificity of the Pap test can be increased by the use of a dual immunocytochemical technique (dual stain) that tests for the co-expression ofp16 and Ki-67. We report our experience using this method on routine diagnostic material.
Design: Residual liquid based cytology cellular material from women with Pap tests interpreted as LSIL was collected between November 2010 and May 2011 and analyzed for p16 and Ki-67 expression using the dual stain. Cases were scored as positive if at least one dual-stained cell was present and negative otherwise, independent of cell morphology. Interpretation was performed by the three authors. Correlation with subsequent cervical histology was performed.
Results: The study set included 231 dual-stained Pap test slides (165 Surepath and 66 Thinprep) from women ranging in age from 17 to 62 (mean 30). Of these, 205 had correlative histology, with CIN 1 in 49.8%, CIN 2 in 10.7%, and CIN 3 in 7.8%. The dual stain was positive in 199 (86.1%) overall and in 175 (85.4%) of those with histologic correlation. Regarding cases with CIN1+ histology, the dual stain was positive in 126/140 (sensitivity 90.0%). For CIN2+ histology, the dual stain was positive in 37/38 (sensitivity 97.4%). Specificity was 24.6%for CIN1+ and 17.4% for CIN2+.
Conclusions: The dual stain can be performed in a routine histology laboratory with commonly used equipment and was easily interpretable independent of cellular morphology. Dual immunocytochemistry using p16 and Ki-67 on Pap test cells interpreted as LSIL yielded a high sensitivity for the detection of CIN2+ lesions on cervical histology, with specificity similar to that obtained with Pap test plus oncogenic HPV testing.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 45, Tuesday Morning