Improving Identification of CIN2+ Disease by Combining MCM2 and MCM7 Biomarker Over-Expression with a Pap Counterstain on a Standard Cervical LBC Specimen.
Clark M Whitehead, Qin He, Lisa Allen, Kellie Willse, Ramona Nelson, Roxanne Hudson, Hema Doobay, Dondrea Purnell, Lawann Simpson, Adriann Taylor, Timothy J Fischer, Douglas Malinowski. BD Diagnostics, Durham, NC
Background: Over-expression of MCM 2 and 7 have been shown to correlate with aberrant S-phase induction and persistent HPV infection. To further improve accuracy in identifying abnormal cells and true disease from BD SurePath liquid-based cervical (LBC) cytology specimens, a new automated test, that combines the morphology of a standard SurePath Pap with protein biomarker immunostaining on a single slide (hereafter referred to as SurePath Plus), was developed. This research study evaluated the performance of SurePath Plus in identifying CIN2+ disease.
Design: This study included 996 cytology specimens ranging from NILM to HSIL. All LSIL and HSIL cases had biopsy results. As biopsies were not obtainable for all NILM and ASCUS cases, a negative HPV test was used as a surrogate for disease negative status. For each sample, 2 slides were produced, one prepared as a SurePath Pap and a second SurePath Plus slide prepared using a BD PrepStain Plus instrument that combines cell deposition with optimized immunocytochemical processing and Pap counterstaining. All slides were scored using standard Bethesda 2001 criteria. The SurePath Plus slide was further evaluated for the presence of nuclear immunostaining in morphologically abnormal cells. The distribution of cases within the various morphologic categories and their biopsy status were compared.
Results: Comparison of the SurePath Plus slides to the SurePath Pap slides, using a cytology endpoint, resulted in a 153% increase in the HSIL+ detection rate (123 cases) and a corresponding decrease in detection rates for LSIL (23% decrease, 58 cases) and ASCUS (54 % decrease, 207 cases). The biopsy endpoint analysis resulted in a significant increase in the number of CIN2+ cases associated with HSIL+ cytology and a corresponding reduction in the amount of CIN2+ within the LSIL and ASCUS groups for the SurePath Plus Test when compared to the SurePath Pap. Specifically, the number of CIN2+ cases within the HSIL+ group increased 154% (77 cases), while the number of CIN2+ cases decreased by 62% (52 cases) within the LSIL and 62% (13 cases) for the ASCUS population.
Conclusions: This study reports the successful development of reagents, assay, and instrumentation that combine biomarker specific immunostaining with standard Pap counterstaining. The use of the SurePath Plus test leverages the advantages of both biomarker expression and morphologic assessment on a single LBC slide. Within this biopsy confirmed research cohort, the SurePath Plus test resulted in a more accurate detection of high grade disease.
Category: Gynecologic & Obstetrics
Monday, February 28, 2011 1:15 PM
Platform Session: Section C, Monday Afternoon