P-ERM, a Marker of Cell Polarity, Distinguishes Tubal Intraepithelial Carcinoma from Benign Oviductal Mucosa
Gang Ning, Ju Yuan, In Young Hwang, Michelle S Hirsch, Frank D McKeon, Christopher P Crum, Wa Xian. Harvard Medical School, Boston, MA; Institute of Medical Biology, A*STAR, Singapore; Brigham and Women's Hospital, Boston, MA; University of Massachusetts Medical Center, Worcester, MA
Background: Serous tubal intraepithelial carcinoma (STIC) is a non-invasive phase of pelvic serous cancer at risk for metastasizing. Because of its biologic significance, its accurate distinction from non-malignant mimics is important. This can be achieved in part by the application of histologic criteria and immunostaining with biomarkers (p53, Ki-67). However, consistently distinguishing STIC from proliferative or expansile lesions with p53 mutations (p53 signatures) remains difficult. Loss of cell orientation is an important feature of STIC. Certain proteins, such as Ezrin-Radaxin-Moesin (ERM) are involved in cytoskelaton organization and when activated (phosphorylated or P-ERM) concentrate on the apical cytoplasmic membrane of polarized epithelia. We sought to determine if P-ERM would be useful in distinguishing STIC from its benign couterparts in oviductal mucosa.
Design: A range of oviductal epithelia, including STICS (20), serous carcinomas (10), benign secretory outgrowths (SCOUTs) with (p53 signatures, 4) and without altered p53 staining (10), and expansile or proliferative p53 signatures (3) were immunostained with an antibody to P-ERM. Staining patterns were compared with attention to their location and intensity.
Results: P-ERM staining was linear and luminal in normal mucosa, with weaker staining of the cell membranes. In STICS, the luminal staining was either lost or disrupted, producing a discontinuous pattern, with increased staining of individual cell membranes, a feature also seen in invasive carcinomas. Expansile or proliferative p53 signatures maintained the apical staining with variable cell membrane staining. Other SCOUTs and normal epithelium displayed a similar staining pattern. The intensity of P-ERM staining in the former was less but not accompanied by conspicuous staining of individual cell membranes. There was no apparent relationship between P-ERM staining and proliferation (MIB1).
Conclusions: We show, for the first time, that an immunohistochemical correlate of cell polarity (P-ERM) shows an altered expression pattern in STIC that will distinguish it from its benign counterparts, including proliferative p53 signatures. If confirmed this finding warrants further analysis of this and other indices of cell polarity as objective markers for diagnosis and mapping the evolution of early pelvic serous cancer.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 189, Tuesday Morning