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[869] Expression of PAX2 in Endometrial Hyperplasia and Carcinomas: Immunohistochemical Analysis of 136 Cases

D Cao, AM Gown, RS Vang, RJ Kurman, BM Ronnett. The Johns Hopkins Hospital, Baltimore, MD; Seattle, WA

Background: A paired box gene, PAX2, has been reported to be activated by estrogen and tamoxifen in endometrial carcinomas but not in normal endometrium, with activation associated with cancer-linked hypomethylation of the PAX2 promoter (Wu et al, Nature 2005;438:981-7). However, PAX2 expression in normal and hyperplastic endometrium and endometrial carcinomas has not been systematically studied.
Design: Immunohistochemical analysis of PAX2 expression (nuclear staining) using a rabbit polyclonal anti-PAX2 (1:50 dilution, Zymed Laboratories Inc., San Francisco, CA) was performed on 136 endometrial specimens: non-atypical hyperplasia (simple or complex [SH/CH]; n=22), complex atypical hyperplasia (CAH, n=31), FIGO grade 1 endometrioid carcinoma (EC-G1; n=24), FIGO grade 2 endometrioid carcinoma (EC-G2; n=28), FIGO grade 3 endometrioid carcinoma (EC-G3; n=19), and serous carcinoma (invasive or endometrial intraepithelial carcinoma [SC/EIC]; n=12).
Results: Staining of lesional cells was semi-quantitatively scored: 0 = <5% , 1+ = 5-25%, 2+ = 26-50%, 3+ = 51-75%, 4+ = >75% (Table 1). Normal endometrial glands, when present, were uniformly positive (usually 4+, rarely 3+) and served as internal positive control.
Conclusions: PAX2 was uniformly expressed in normal endometrium and demonstrated progressive loss along the spectrum of endometrial proliferations considered pathogenetically related to unopposed estrogenic stimulation (hyperplasias and endometrioid carcinomas). In contrast, loss of expression in serous carcinomas was less frequent compared with endometrioid carcinomas. These results appear contrary to the concept of PAX2 gene activation in carcinomas related to estrogenic stimulation, suggesting a need for further analysis, including correlation of PAX2 and ER expression with PAX2 promoter methylation status, and comparison of results with this polyclonal anti-PAX2 with a monoclonal anti-PAX2.

Table 1: PAX2 expression in endometrial hyperplasia and carcinomas
Endometrial lesion01+2+3+4+
SH/CH (n=22)4 (18%)5 (23%)3 (13%)5 (23%)5 (23%)
CAH (n=31)17 (55%)7 (23%)2 (6%)2 (6%)3 (10%)
EC-G1 (n=24)19 (79%)1 (4%)1 (4%)0 (-)3 (13%)
EC-G2 (n=28)22 (79%)1 (3%)2 (7%)0 (-)3 (11%)
EC-G3 (n=19)18 (95%)0 (-)0 (-)1 (5%)0 (-)
SC/EIC (n=12)6 (50%)4 (33%)0 (-)2 (17%)0 (-)



Category: Gynecologic

Monday, March 26, 2007 8:15 AM

Platform Session: Section C, Monday Morning

 

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