Immunohistochemical Panel To Differentiate Endometrial Papillary Serous Carcinoma from High Grade Endometrioid Carcinoma
MA Rollins-Raval, R Byler Dann, RP Edwards, G Tseng, M Chivukula. Magee-Womens Hospital of UPMC, Pittsburgh, PA; University of Pittsburgh, Pittsburgh, PA
Background: Endometrial papillary serous carcinoma (EPS) can be difficult to differentiate histologically from high grade endometrial endometrioid carcinoma (EE). Recurrences have been found to be more frequent in EPS as opposed to high grade EE despite the same pre- and post-operative radio- and chemotherapy, indicating more aggressive tumor biology. To date, there is no well-defined immunohistochemical (IHC) panel to differentiate these two tumors.
Design: 12 cases of EE and 23 cases of EPS were retrieved from departmental archives and stained using Pax-2, WT-1 and p16 antibodies. PAX2, a homeobox gene, encodes a transcription factor expressed in intermediate mesoderm from which Wolffian and Mllerian ducts, and kidneys originate, whose expression was demonstrated in epithelial cells of the female genital tract, as well as ovarian serous carcinoma (OSC). Wilm's tumor gene (WT1) plays a role in early stages of development of kidneys and gonads, and its product is expressed in OSC. P16, a tumor suppressor gene involved in cervical carcinogenesis, is shown to be expressed in high grade carcinomas of Mllerian origin. A strong nuclear staining is considered positive for the former two anitibodes, with strong nuclear or nuclear and cytoplasmic staining for the latter. Statistical analysis via Fisher's Exact test is performed to compare proportions of antibody positivity in these two entities.
Results: See Table-1.
Table-1. Summary of IHC staining intensity in EPS and EE*Negative/Weak=Negative; Moderate/Strong=Positive
Statistical analysis of individual markers and combined panel with p-values: WT-1: 8/23 (34.8%) in EPS to 0/12 (0%) in EE; p-value = 0.02 (Sensitivity, specificity for EPS: 34.8%, 100%). Pax-2: 15/23 (65.2%) in EPS to 4/12 (33.3%) in EE; p-value=0.08 (Sensitivity, specificity for EPS: 65.2%, 66.7%). p16: 22/23 (95.7%) in EPS to 6/12 (50%) in EE; p-value=0.003 (Sensitivity, specificity for EPS: 95.7%, 50%); A combination of the three markers: 17/23 (73.9%) in EPS to 2/12 (16.7%) in EE; p-value=0.002 (Sensitivity, specificity for EPS: 73.9%, 83.3%).
Conclusions: WT-1 is specific and p16 is fairly sensitive for EPS. Positive expression existing in two or more biomarkers is predictive of EPS; otherwise it is predicitive of EE.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 163, Monday Morning