Utility of PAX2 as a Marker for Diagnosis of Endometrial Intraepithelial Neoplasia (EIN).
Charles M Quick, Anna R Laury, Nicolas M Monte, George L Mutter. Brigham and Women's Hospital, Boston, MA
Background: Accurate diagnosis of premalignant endometrial disease, EIN, requires learning new diagnostic criteria and resolving its many mimics. PAX2, a gene clonally inactivated in three quarters of EIN lesions, is a potential tool for educational and/or diagnostic use. When informative, PAX2 can precisely delimit lesion extent and facilitate appreciation of lesion characteristics relative to background. We had two trainees diagnose routinely stained (“H&E”) biopsies and then measured the effect of subsequently viewing a PAX2 stain on their interpretation.
Design: H&E recuts and PAX2 immunostained sections from 52 endometrial biopsies originally diagnosed as EIN were assembled (by GLM and NM) as a study set, and presented to two pathology fellows (MQ and AL, “subjects”) for review. 71% (37/52) of the EINs were known to be PAX2 null. The subjects first diagnosed H&E slides using standard EIN criteria, recording those features that complicated diagnosis. PAX2 stains were then reviewed in all cases and problems and benefits of their interpretation noted.
Results: Results of 52 cases and two reviewers totalled 104 diagnostic passes. H&E diagnoses included EIN (82%), and crowded glands subdiagnostic of EIN (12%). Diagnostic areas seen on the original slides were depleted in some recuts. The most common features confounding H&E EIN diagnosis were altered differentiation (“metaplasia”, 14%), separation of EIN and background glands within different tissue pieces (13%), large lesions lacking comparison normal endometrium (11%), and secretory background (8%). Trainees were more likely to consider PAX2 staining helpful when there was a secretory background, or foci of EIN lacked adjacent normal tissue in the diagnostic fragment. PAX2 staining confused the subjects where interpretation of PAX2 immunoreactivity was unclear (14%), and when non-diagnostic tissue fragments contained PAX2 null glands (11%).
Conclusions: PAX2 staining is not a panacea for resolution of all, or even most, EIN lesions. Some do not bear abnormalities of this marker, and others are difficult to interpret. There is, however, educational value in using small training sets of dual stained EIN lesions to illustrate patterns of lesion spread and variable presentations of EIN cytology and architecture. PAX2 immunostaining may have clinical value in carefully selected cases where contrast between the lesion and background are represented in different areas of the sample, or obscured by a secretory background.
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 141, Wednesday Afternoon