Clinicopathologic study of the putative precursor lesions of epithelial ovarian cancer in low-risk women

Abstract

Possible precursor lesions for epithelial ovarian cancer (EOC) have been defined in the ovaries of women with contralateral EOC, with breast cancer susceptibility gene (BRCA)-1 mutations, or with positive family history. We aimed to investigate the prevalence of these lesions in women without any recognizable risk and to correlate these lesions with clinical ovulatory markers. The study group consisted of 184 women who were operated for benign gynecological conditions. Patients were requested to fill a questionnaire about anthropometric characteristics and medical and reproductive history. Oophorectomy specimens were examined for presence of epithelial inclusion cysts (EIC), cortical invaginations (CI), stromal hyperplasia (SHPP), epithelial pseudostratification (EPS), and surface papillomatosis (SP). Women with EIC were older, had lower age at menarche, and had higher menarche-to-pregnancy and menarche-to-operation time. SHPP was found to be related with age, menarche-to-operation time, history, and the duration of oral contraceptive use. Women with SP had lower age at menarche, lower menopausal age, and longer duration of hormone replacement therapy. No significant correlations were established between CI and any clinical parameters. Only one patient had EPS. Our findings suggest that these lesions correlate closely with reproductive features. Exact mechanisms that lead to development of these lesions should be clarified before implying them as precursor lesions of EOC.

BRCA1 expression, proliferative and apoptotic activities in ovarian epithelial inclusions

“…In this study, we examined two sections per ovary and observed OEIs in 53% of women examined, which is similar to previous findings [31]. It has been reported that the incidence of OEIs increases with age [31, 32]. In this study, OEIs were more common in the ovaries of postmenopausal women (58%) than of premenopausal women (45%), but there was no trend of increasing numbers of OEIs with age in premenopausal women.…”

Insulin and insulin-like growth factor signaling increases proliferation and hyperplasia of the ovarian surface epithelium and decreases follicular integrity through upregulation of the PI3-kinase pathway

“…Activation of this pathway may also repress expression of E-cadherin, a component of the epithelial cell tight junction that functions to establish and maintain cell polarity that is often altered in ovarian cancer cells to permit increased metastasis [43]. While no universally accepted precursor lesion exists for ovarian cancer originating in the OSE, menopausal ovaries and some mouse models of ovarian cancer exhibit hyperplasia of the OSE, formation of papillary structures, and inclusion cysts [44,45]. Insulin and IGF-I did not induce transformative changes in OSE as measured by growth in soft agar (data not shown); however, it is possible that if levels of insulin and IGF accumulate enough locally in disease they might act on early stages of ovarian cancer to increase proliferation and alter cell polarity to encourage hyperplasia.…”

Ovarian Epithelial Dysplasia and Prophylactic Oophorectomy for Genetic Risk

“…This statistical comparison with a control group is necessary because there is no threshold score for dysplasia. 24 For our study, we adopted and extended the score devised by Nieto et al We listed the cytological and architectural abnormalities that were most frequent and most representative of ovarian dysplasia after an exhaustive literature review (which also ensured excellent reproducibility and comparability for our study): ovarian dysplasia found in areas adjacent to stage 1 ovarian carcinoma, 21,25 in the controlateral ovary of women with stage 1 ovarian carcinoma, 26,27 in relation to ovulation induction, 22 and in prophylactic oophorectomy for BRCA mutation. 16,18,19 We incorporated all of these anomalies in order to have a complete dysplasia scoring system (Table 7).…”