[1179] PTEN Status in Untreated and Progestin-Treated 'Complex Endometrial Hyperplasia' and Its Correlation with Disease Outcome

RA Simon, CJ Sung, WD Lawrence, MM Steinhoff, K Hansen, MR Quddus. Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, RI

Background: Complex endometrial hyperplasia without atypia (CEH) according to the WHO is defined by architecturally complex glands without significant cytologic atypia and a relatively low chance of progression to atypical endometrial hyperplasia (AH) or endometrioid carcinoma (EMCA). Other classifications, such as endometrial intraepithelial neoplasia (EIN), maintain that marked glandular crowding is a cardinal feature and that ∼44% of CEHs correspond to, and represent 29% of, EINs. PTEN, a tumor suppressor gene, is reported to be mutated (PTEN-null) in 55-83% of endometrial precancers and EMCAs, respectively. We studied 23 cases of CEH treated with progestins i) to assess the PTEN status before the start of treatment and any change in PTEN status post progestin therapy and ii) to assess any association between post treatment PTEN status and disease resolution, persistence, or progression to AH or EMCA.
Design: From our institutional archives we identified 23 cases of CEH that had been treated with progestin and had available post-treatment samples. The initial biopsy and post-treatment samples (varied from 2-12) were retrieved and immunostained for PTEN (Cascade Bioscience; 1:100 dilutions). Histological changes of progression, regression and persistence were noted. The median follow-up was 35 months (range: 1-114 months).
Results:

Tabke 1: PTEN status before and after progestin therapy

PRE-progestin PTEN status	6 PTEN-null	9 Mixed PTEN-null and PTEN+	8 PTEN+
POST-progestin PTEN status	4 PTEN-null; 0 Mixed; 2 PTEN+	1 PTEN-null; 3 Mixed; 5 PTEN+	0 PTEN-null; 2 Mixed; 6 PTEN+

Table 2: Post-progestin therapy follow-up

POST-progestin PTEN status	5 PTEN-null	5 Mixed PTEN-null and PTEN+	13 PTEN+
Post-progestin follow-up	2 Progressed; 3 Regressed; 0 No change	3 Progressed; 1 Regressed; 1 No change	3 Progressed; 10 Regressed; 0 No change
Final pathology	2 EMCA	3 AH	2 AH; 1 EMCA

Conclusions: 65% of CEH exhibited PTEN mutation prior to progestin therapy, whereas 43% showed PTEN mutation after therapy. In 13 cases (57%) of CEH the PTEN status remained unchanged after progestin treatment. Half of progestin-treated PTEN-null cases of CEH progressed to AH/EMCA while 23% of progestin-treated PTEN+ cases progressed to AH/EMCA. These suggest that the PTEN status of CEH may be used in predicting its biologic behavior after progestational therapy and in determining the frequency of clinical follow-up studies.
Category: Gynecologic & Obstetrics

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 163, Monday Morning