Progesterone Receptors A and B, pAkt, and p4EBP1 Expression Patterns in Grade 1 Endometrial Adenocarcinoma(G1EAC) and Complex Atypical Hyperplasia(CAH) and Prediction of Response to Progestin Therapy.
Kristine R Penner, Madhuri Wadehra, Angela A Steinhardt, Claire P Hogue, Ilana E Cass, Christine S Walsh, Christine H Holschneider, Jonathan Braun, Oliver Dorigo. UCLA Medical Center, Los Angeles, CA; Olive View-UCLA Medical Center, Los Angeles, CA; Cedars Sinai Medical Center, Los Angeles, CA
Background: Progestin therapy is a treatment option for CAH and G1EAC in women who desire fertility preservation.No markers that reliably predict response to treatment have been identified.Progesterone receptor status and activation of the pAkt/PTEN pathway have each been hypothesized to influence the effectiveness of progestin treatment.Progesterone receptor B(PRB)activation is known to alter the activity of this pathway.We investigated whether expression of progesterone receptor A(PRA) and B(PRB) as well as markers in the pAkt/PTEN pathway (pAkt and p4EBP1) change in response to progestin therapy and if any of these markers could be used to predict therapeutic response.
Design: Premenopausal patients with CAH or G1EAC who underwent progestin therapy for at least 8 weeks between 1998-2007 were retrospectively identified from three institutions.Patients had an initial diagnostic endometrial biopsy and a follow-up biopsy during the first nine months of treatment.Immunohistochemical(IHC) staining for PRA, PRB, pAkt and p4EBP1 was performed on all tissue.The H score system was used by a pathologist to quantify the IHC staining.H score>50 is considered positive with 50-100 weakly positive, 100-200 moderately positive, and 200-300 strongly positive.Tumor tissue was scored separately from stroma.
Results: 38 subjects were identified with a median age of 36 years(range 23-48).Moderate staining(H score >100)for PRA, PRB and pAkt was seen in 79%, 84%,and 62% of initial biopsies,respectively.Expression levels of all markers(PRA, PRB, pAkt, p4EBP1)were greater in the initial biopsy than after treatment (p<0.05).Strong(H score >200) expression of PRB in the initial biopsy was significantly associated with resolution(83% vs. 44% resolution,p=.035).
Conclusions: Our data suggests that progestin therapy appears to reduce expression of PRA, PRB, pAkt, and p4EBP1 in CAH and G1EAC, and hence,may influence activation of the pAkt/PTEN pathway.Strong PRB expression in both the initial and first follow-up biopsies with CAH or Grade 1 EA has the potential to predict response to progestin treatment.Staining for PRB in a patient's initial diagnostic biopsy therefore may provide additional information to assist in counseling patients regarding their individual likelihood of resolution of G1EAC and CAH with progestin therapy.
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 145, Wednesday Afternoon