Unraveling the two entities of endometrioid ovarian cancer: A single center clinical experience
Highlights
► Endometriosis-associated endometrioid ovarian tumors possess a different biologic signature when compared to cancers not associated with the disease. ► Clinical and molecular features of the two types of endometrial cancer reflect those of endometriosis-associated and non-associated endometrioid ovarian tumor.
Introduction
The potential for neoplastic degeneration of ovarian endometriotic cysts has been debated over the past decade from biological, epidemiological and clinical perspectives [1], [2], [3], [4], [5]. This issue is of particular clinical relevance given the high incidence of endometriosis, a disease affecting an estimated 14 million women of reproductive age in the European Union alone [6]. The life-threatening characteristics of ovarian cancer, a tumor with a 5-year overall survival of less than 40%, make the issue even more critical. Indeed, based on a comprehensive literature search, a significant association between endometriosis and ovarian cancer has been supported by at least six sufficiently powered epidemiological studies [1], [7], [8], [9], [10], [11]. In addition, when the presence of endometriosis has been related to the cancer histotypes, it was clear that tumors arising from endometriosis were confined to specific subcategories of disease [3]. A strong association between endometriosis and both endometrioid and clear cell ovarian cancers has long been known, although the adoption of strict criteria for the pathological analysis has prevented for decades the recognition of ectopic endometrium as the definitive site of origin of these gonadal malignancies [3], [12]. Currently, atypical endometriosis, observed in 1–3% of endometriotic cysts [13], is considered the precursor lesion for most endometrioid and clear cell ovarian cancers and the risk of detecting these histotypes is estimated to be about 4-fold higher in women with endometriosis [14].
A keenly debated topic in literature is whether endometriosis-associated cancer represents a clinicopathologic entity distinct from other forms of ovarian cancers [13], [14], [15]. Indeed, increased awareness of the characteristics of these tumors would improve early detection of patients at risk. To this aim, some studies have investigated the clinical behavior and prognostic factors in ovarian cancer patients with or without concomitant endometriosis. In general, they suggest, albeit not consistently, that patients with endometriosis tend to be younger and to be diagnosed in earlier stages and with lower grade lesions [16], [17], [18]. Other studies have tried to establish the histological features characterizing these ovarian cancers. Reports are however heterogeneous with controversial results in terms of prevalence and significance of metaplastic, hyperplastic or atypical changes associated with the malignant lesions [3]. Importantly, very few of these studies have specifically evaluated differences in prognostic factors and histological findings between cancers of similar histotypes [11], [19], [20], [21], [22], [23], [24]. The comparisons have been mostly performed with cases of ovarian epithelial cancer in general, thus probably introducing some sources of bias.
In this study, we have evaluated the clinical and histological features of endometriosis-associated ovarian cancers of the endometrioid histotype specifically and compared them with those of endometrioid tumors without endometriosis. Based on the combination of the results obtained herein and of findings derived from the molecular pattern, some potentially interesting observations on the pathogenesis of endometrioid ovarian cancer have been suggested as a potential novel theory.
Section snippets
Methods
After obtaining ethical approval from San Raffaele Institute Ethics Board, the study population was identified through a search on the Gynecological Malignancies Database of the Department of Obstetrics and Gynecology.
Between January 2000 and December 2010, n = 658 patients were diagnosed with ovarian cancer at the Department of Obstetrics and Gynecology of the San Raffaele Scientific Institute. All patients with a primary diagnosis of invasive ovarian tumor of endometrioid histotype were
Results
Medical records and pathologic specimens were available for n = 65 patients diagnosed with endometrioid ovarian cancer (9.9%) in the considered time interval. Of these n = 65 patients, n = 21 (32%) had EAEOC and 44 (68%) had EOC. Clinical and morphological characteristics of the two groups are shown in Table 1. The mean age ± SD at diagnosis of the entire cohort was 60 ± 12 (range 37–87). Overall, age was significantly lower in patients without endometriosis (mean ± SD, 55 ± 10; range 39–73) versus
Discussion
The rate of malignant transformation of endometriosis into ovarian cancer has been estimated to be between 0.7% and 5% [28]. It is clinically well known that about one-third of all endometrioid and clear cell ovarian cancers arise from endometriosis. However, the distinguishing clinico-pathological features of endometriosis-associated ovarian tumors are still controversial. Some investigators have suggested that these tumors may be associated with young age, early-stage, low grade disease, and
Conclusions
We have herein confirmed that EAEOC presents at a younger age with an earlier stage and lower grade. Moreover, based on the fact that we detected a higher rate of concurrent endometrial cancer in EAEOC and considering the molecular data published so far, we dare to hypothesize a parallelism between endometrial and endometrioid ovarian carcinoma. This hypothesis represents the focus of our current and future research.
Conflict of interest statement
The authors declare no conflict of interest.
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