Loss of PTEN Expression but Intact Expression of Mismatch Repair Proteins (MLH-1 and MSH-2) in Atypical Polypoid Adenomyomas of the Uterus.
Michael Cruise, Teri Longacre, Edward Stelow. University of Virginia, Charlottesville; Stanford, Stanford, CA
Background: hosphatase and tensin homolog (PTEN) is a tumor suppressor gene located at 10q23 that encodes a phosphatase that works within the AKT pro-apoptotic pathway and the MAPK pathway to regulate cellular growth as well as other functions. Mutations of PTEN have been implicated in inherited cancer syndromes such as Cowden disease. Patients with this disease typically develop multiple hamartomatous tumors and are at increased risk for breast, thyroid and endometrial cancers. Mutations of PTEN are present in up to 83% of spontaneous endometrial adenocarcinomas, making it the most frequent molecular genetic alteration seen with these tumors. Additionally, deficiencies in mismatch repair proteins are frequently seen with endometrial carcinoma. Recently, we encountered a patient with Cowden syndrome who developed an atypical polypoid adenomyoma (APA) of the uterus which prompted an investigation of the prevalence of loss of PTEN and mismatch repair protein( MHL1 and MSH2) expression in APAs.
Design: A series of APAs were reviewed and diagnoses were confirmed. These included a mixture of curettage and hysterectomy/polypoidectomy specimens. PTEN, MLH1, and MSH2 expression was examined using immunohistochemistry in formalin-fixed, paraffin-embedded tissue. Cases were considered to be PTEN reactive if they demonstrated cytoplasmic staining of the glandular component of the APA and non-reactive if there was no cytoplasmic staining of the glandular component but the stroma or other internal control tissues was reactive. Similarly, MLH1 and MSH2 were considered positive with nuclear staining of the neoplastic cells, and negative if the neoplastic cells were negative but an internal control was positive.
Results: Immunohistochemical staining for PTEN demonstrated a total of 12 of 20 (60%) cases with staining of the glandular component of the lesion. A total of 7 of 20 cases demonstrated stromal and/or squamous metaplasia positive for PTEN but no staining of the glandular component. All of the cases retained expression of MLH1 and MSH2.
Conclusions: PTEN expression is lost in a subset of APAs, albeit less so than is seen with endometrial carcinomas. There was no loss in the expression of mismatch proteins. Uncommonly, APAs develop in patients with Cowden disease.
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 175, Wednesday Afternoon