Involution of latent endometrial precancers by hormonal and nonhormonal mechanisms.
BACKGROUND
Inactivation of the PTEN suppressor gene has been shown to occur in the majority of endometrial cancer cases. Somatic PTEN inactivation by deletion and/or mutation, the first detectible change of endometrial carcinogenesis, has been reported to occur at a high frequency in the endometrium of normal premenopausal women, although few of these cases progress to cancer. It was hypothesized that the 50% to 60% reduced cancer risk attributed to oral contraceptives (OCPs) and intrauterine devices (IUDs) occurred in part through their activity as negative selection factors for these subclinical mutated glands.


METHODS
A total of 71 women with a history of OCP use and 80 with a history of IUD use were age matched with 191 and 119 controls, respectively. Endometrial biopsy specimens were immunostained for PTEN, and each was scored for the presence or absence of PTEN-null glands (latent precancer).


RESULTS
The frequency of latent precancers was found to be significantly reduced in OCP-exposed (13%; odds ratio [OR], 0.19 [P < .001]) and IUD-exposed (18%; OR, 0.42 [P = .015]) women compared with respective matched controls (43% and 34%). The presence or absence of endometritis did not appear to be significantly correlated with PTEN status within the IUD-exposed group (P = .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 reported to diminish the incidence of endometrial cancer 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.
Lin
Ming-Chieh
MC
Department of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.
Burkholder
Kyla A
KA
Viswanathan
Akila N
AN
Neuberg
Donna
D
Mutter
George L
GL
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D016022:Case-Control Studies; D003276:Contraceptives, Oral; D003430:Cross-Sectional Studies; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007434:Intrauterine Devices; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000032:analysis*; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D017697:Premenopause; D012306:Risk
D014408:Biomarkers, Tumor; D003276:Contraceptives, Oral; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human