Involution of Latent Endometrial Precancers by Hormonal and Non Hormonal Mechanisms
MC Lin, KA Burkholder, AN Viswanathan, D Neuberg, GL Mutter. Brigham and Women's Hospital, Boston, MA; Dana Farber Cancer Institute, Boston, MA
Background: Inactivation of the PTEN suppressor gene occurs in the majority of endometrial cancer cases. Somatic PTEN inactivation by deletion and/or mutation, the first detectible change of endometrial carcinogenesis, occurs at a high frequency in the endometrium of normal premenopausal women, though few of these progress to cancer. We hypothesized that the 50-60% reduced cancer risk of oral contraceptives (OCP) and intrauterine devices (IUD) occurs in part through their activity as negative selection factors for these subclinical mutated glands.
Design: 71 women with a history of oral contraceptive use and 80 with a history of IUD use were age matched with 191 and 119 controls, respectively. Endometrial biopsies were immunostained for PTEN and each scored for presence or absence of PTEN null glands (latent precancer).
Results: The frequency of latent precancers was significantly reduced in OCP (13%, OR 0.19, p<0.001) and IUD (18%, OR 0.42, p=0.015) exposed women compared to respective matched controls (43 and 34%). Presence or absence of endometritis did not significantly correlate with PTEN status within the IUD exposed group (p=0.24).
Conclusions: Normal appearing PTEN mutated endometrial glands, which are highly prevalent in the normal population, may be targets of endometrial cancer risk modulating exposures. Some exposures known to diminish endometrial cancer occurrences in epidemiologic outcome studies, including OCP and IUD use, are associated with a proportionate decline in the frequency of latent precancers. Involution of pre-existing endometrial latent precancers, as evaluated by PTEN analysis, may provide an accessible surrogate marker for long term endometrial cancer risk.
Tuesday, March 10, 2009 8:15 AM
Platform Session: Section D, Tuesday Morning