We have analyzed the overall survival further in cases with and without endometriosis in strata of selected characteristics (Table 2). The presence of endometriosis was associated with higher 10-year overall survival (OS) rates in E ovarian cancer cases (HR, 0.2; 95% CI, 0.3–1.4). In particular, the 10-year OS was 100% among women with E ovarian cancer grade 1 to 2 and endometriosis, but this estimate was based on 12 cases.
This study’s results show that EAOC CC and E cases tended to have a better long-term survival than non-EAOC CCs and E ones. In particular, the 10-year OS was approximately 90% among women with E ovarian cancer and endometriosis, but this estimate was based on 17 cases.
The favorable prognostic role of endometriosis was, however, largely explained by the different stage distribution between the 2 groups: early stages being significantly more common among EAOC cases than among those without endometriosis.
Potential limitation of this analysis should be considered. First, this is a retrospective analysis, and data were obtained by clinical records; thus, only hard information, such as age and stage of the disease, were collected. The considered cases were observed during 20 years. During this long period, treatment protocols changed. Likewise, the pathologic criteria may change overtime. In particular, the attention given to the diagnosis of endometriosis in ovarian cancer cases may be changed. The frequency of EAOC cases did not increase among CC and E cases during the study period. Furthermore, the clinical and pathologic staff was largely unchanged over the considered period.
Another limitation of this study is that we were not able to identify ovarian cancer cases in which the cancer was arising in endometriosis and cases in which endometriosis was incidentally found in the surgical specimen, but not in continuity with the tumor.
Endometriosis was diagnosed in 53% of CC ovarian cancer cases and 47% of E ones. These findings are largely consistent with published data.6–14 For example, in a study that included 221 endometrial epithelial ovarian cancer cases, endometriosis was identified in 82 (37.1%).6 Similar estimates were reported in other studies.7–9
Endometriosis-associated ovarian cancer cases have been suggested to be diagnosed at an early stage. For example, a case control study including 58 EAOC patients and 234 age-matched non-EAOC patients conducted in Slovenia showed that EAOC cases had a statistically significant lower-stage disease (both FIGO and TNM).4 Similar findings have been reported in other studies.5,15 A greater proportion of stage I among EAOC cases has been observed in the present study.
It has been suggested that the lower stage at diagnosis in ovarian cancer cases with endometriosis is due to the presence of endometriosis, and its symptoms may cause early diagnosis of the diseases.16 However, Orezzoli et al (2008)5 have shown that most patients with EAOC had cancer-related symptoms. Otherwise, it is conceivable that ovarian cancer case arising on endometriosis may have a more benign profile.
Younger age has also been associated with diagnosis of EAOC cases. In the study conducted by Orezzoli et al (2008),5 patients with CC carcinoma arising in endometrioisis were 10 years younger than those with CC cancer not arising in endometriosis (P < 0.05). In our series, cases with endometriosis were, on average, 3 years younger than those without endometriosis, but the finding was not statistically significant.
The role of endometriosis ovarian cancer prognosis is unclear in the literature. Published studies have generally showed that patients with EAOC had higher survival rates, but in most series, this finding was explained by the higher proportion of early stages among ovarian cancer cases with endometriosis.4,5
For example, in the previously quoted study by Erzen et al4 (2001), patients with EAOC showed a significantly better overall survival. This better survival was evident in all age groups and histologic subtypes but not in any FIGO stage.
Orezzoli et al5 have recently analyzed the role of the presence of endometriosis as a prognostic factor in 84 patients with CC carcinoma of the ovary. In that study, endometriosis was diagnosed in 49% of cases: in 18%, cancer arose in endometriosis, and in 31%, endometriosis was found elsewhere in the specimen. The median OS for patients with endometriosis was 196 months versus 34 months in those without endometriosis. In the interpretation of this finding, the authors underlined that it is possible that the effect on survival associated with the presence of endometriosis might reflect primarily the strong relation between the presence of endometriosis and stage at diagnosis.5
Modesitt et al,15 however, did not find any difference in survival among cases with and without endometriosis.
In our study, overall 5-year survival rate in early-stage cases tended to be higher in women with endometriosis (HR, 0.4; 95% CI, 0.1–2.0). The finding, however, was not statistically significant.
In biological terms, it has been shown17 that ARID1A (AT-rich interactive domain-containing protein 1A) mutations is common in ovarian CC carcinomas, E carcinomas, but not in high-grade serous ovarian carcinomas. In particular, the loss of the BAF250a protein has been shown strongly associated with the ovarian CC carcinoma and E carcinoma subtypes and the presence of ARID1A mutations. Interestingly, these mutations have been observed in contiguous atypical endometriotic lesions, but not in distant endometriotic lesions far from the carcinoma. Furthermore, in the E ovarian cancers, breast cancer gene inactivation has not been reported.18
In conclusion, this analysis shows that EA CC and E ovarian cancer cases are diagnosed at an earlier stage than cases without endometriosis.
No clear association emerged between presence of endometriosis and survival: EA CC and E ovarian cancer cases tended to have a more favorable prognosis, but this finding was at least in part explained by the higher proportion of stage I and II cases in this group.
1. Somigliana E, Vigano P, Parazzini F, et al.. Association between endometriosis
and cancer: a comprehensive review and a critical analysis of clinical and epidemiological evidence. Gynecol Oncol
. 2006; 101: 331–341.
2. Melin A, Sparen P, Persson I, et al.. Endometriosis
and the risk of cancer with special emphasis on ovarian cancer
. Hum Reprod
. 2006; 21: 1237–1242.
3. Brinton LA, Gridley G, Persson I, et al.. Cancer risk after a hospital discharge diagnosis of endometriosis
. Am J Obstet Gynecol
. 1997; 176: 572–579.
4. Erzen M, Rakar S, Klancnik B, et al.. Endometriosis
-associated ovarian carcinoma (EAOC): an entity distinct from other ovarian carcinomas as suggested by a nested case-control study. Gynecol Oncol
. 2001; 83: 100–108.
5. Orezzoli JP, Russell AH, Oliva E, et al.. Prognostic implication of endometriosis
in clear cell carcinoma of the ovary. Gynecol Oncol
. 2008; 110: 336–344.
6. Lim MC, Chun KC, Shin SJ, et al.. Clinical presentation of endometrioid epithelial ovarian cancer
with concurrent endometriosis
: a multicenter retrospective study. Cancer Epidemiol Biomarkers Prev
. 2010; 19: 398–404.
7. McMeekin DS, Burger RA, Manetta A, et al.. Endometrioid adenocarcinoma of the ovary and its relationship to endometriosis
. Gynecol Oncol
. 1995; 59: 81–86.
8. Fukunaga M, Nomura K, Ishikawa E, et al.. Ovarian atypical endometriosis
: its close association with malignant epithelial tumours. Histopathology
. 1997; 30: 249–255.
9. Deligdisch L, Penault-Llorca F, Schlosshauer P, et al.. Stage I ovarian carcinoma: different clinical pathologic patterns. Fertil Steril
. 2007; 88: 906–910.
10. Ogawa S, Kaku T, Amada S, et al.. Ovarian endometriosis
associated with ovarian carcinoma: a clinicopathological and immunohistochemical study. Gynecol Oncol
. 2000; 77: 298–304.
11. Vercellini P, Parazzini F, Bolis G, et al.. Endometriosis
and ovarian cancer
. Am J Obstet Gynecol
. 1993; 169: 181–182.
12. Valenzuela P, Ramos P, Redondo S, et al.. Endometrioid adenocarcinoma of the ovary and endometriosis
. Eur J Obstet Gynecol Reprod Biol
. 2007; 134: 83–86.
13. Jimbo H, Yoshikawa H, Onda T, et al.. Prevalence of ovarian endometriosis
in epithelial ovarian cancer
. Int J Gynaecol Obstet
. 1997; 59: 245–250.
14. DePriest PD, Banks ER, Powell DE, et al.. Endometrioid carcinoma of the ovary and endometriosis
: the association in postmenopausal women. Gynecol Oncol
. 1992; 47: 71–75.
15. Modesitt SC, Tortolero-Luna G, Robinson JB, et al.. Ovarian and extraovarian endometriosis
-associated cancer. Obstet Gynecol
. 2002; 100: 788–795.
16. Sainz de la Cuesta R, Eichhorn JH, Rice LW, et al.. Histologic transformation of benign endometriosis
to early epithelial ovarian cancer
. Gynecol Oncol
. 1996; 60: 238–244.
17. Wiegand KC, Shah SP, Al-Agha OM, et al.. ARID1A mutations in endometriosis
-associated ovarian carcinomas. N Engl J Med
. 2010; 363: 1532–1543.
18. Kurman RJ, Shih Ie M. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer
—shifting the paradigm. Hum Pathol
. 2011; 42: 918–931.
Keywords:Copyright © 2013 by IGCS and ESGO
Endometriosis; Ovarian cancer; Survival