**Section 3**

**Recent Research Trends** 

308 Endometriosis - Basic Concepts and Current Research Trends

Nisolle, M. and J. Donnez (1997). "Peritoneal endometriosis, ovarian endometriosis, and

Prianishnikov, V. A. (1978). "On the concept of stem cell and a model of functionalmorphological structure of the endometrium." Contraception 18(3): 213-223. Ridley, J. H. and I. K. Edwards (1958). "Experimental endometriosis in the human."

Sasson, I. E. and H. S. Taylor (2008). "Stem cells and the pathogenesis of endometriosis."

Schwab, K. E., R. W. S. Chan, et al. (2005). "Putative stem cell activity of human endometrial

Szotek, P. P., H. L. Chang, et al. (2007). "Adult Mouse Myometrial Label Retaining Cells Divide in Response to Gonadotropin Stimulation." Stem Cells 25(5): 1317-1325. Tamura, M., T. Fukaya, et al. (1998). "Analysis of clonality in human endometriotic cysts

Tanaka, M., S. Kyo, et al. (2003). "Evidence of the monoclonal composition of human

Tanaka, T., S. Nakajima, et al. (2003). "Cellular heterogeneity in long-term surviving cells

Taylor, H. S. (2004). "Endometrial cells derived from donor stem cells in bone marrow

Taylor, R. N., S. G. Lundeen, et al. (2002). "Emerging role of genomics in endometriosis

Te Linde, R. W. and R. B. Scott (1950). "Experimental endometriosis." American journal of

Thibodeau, L. L., G. R. Prioleau, et al. (1987). "Cerebral endometriosis." Journal of

Vercellini, P., M. Meschia, et al. (1996). "Bladder detrusor endometriosis: clinical and

Wolff, E. F., X. B. Gao, et al. (2011). "Endometrial stem cell transplantation restores

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laser capture microdissection and the human androgen receptor (HUMARA)

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obstetrics and gynecology 60(5): 1147-1173.

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Molecular Medicine 15(4): 747-755.

assay\* 1." Fertility and sterility 79: 710-717.

epithelial and stromal cells during the menstrual cycle." Fertility and sterility 84:

based on evaluation of X chromosome inactivation in archival formalin-fixed,

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isolated from eutopic endometrial, ovarian endometrioma and adenomyosis

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1124-1130.

292(1): 81-85.

adenomyotic nodules of the rectovaginal septum are three different entities."

**16** 

*Japan* 

**Endometriosis-Associated Ovarian Cancer:** 

Recent studies indicated that oxidative stress has a causal role in the carcinogenesis of mainly two histological subtypes of ovarian cancer, namely, clear cell carcinoma and endometrioid adenocarcinoma. Because of recurrent hemorrhage in endometrial cysts, excess of reactive oxygen species are produced due to iron deposition, which results in direct genomic mutation of the epithelial cells and exaggeration of oxidative stress by stromal cells such as macrophages. In endometriosis-associated ovarian cancer, genomic mutations in specific genes such as ARID1A, p53, K-ras, PTEN, PI3CA and Met have been reported. Mechanism of carcinogenesis, especially focusing on the precise role of oxidative stress, remains to be clarified. Development of novel drugs and methods for therapy or

Endometriosis is a common disease affecting 10 to 15% of women of reproductive age (Irving, 2011). An association between endometriosis and cancer was reported as early as the 1920s in English publications. Sampson (Sampson, 1925) proposed that endometrial carcinoma of the ovary develops from endometrial tissue, based on classic microscopic observation using several strict criteria (i.e., the coexistence of benign and malignant tissue with a shared histologic relationship in the same organ and evidence against invasion from other sites or sources). Further studies were interrupted by World War II; however, in the late 1940s and 1950s, several groups published case reports that met Sampson's criteria (Scott, 1953; Postoloff & Rodenberg, 1955). Although none of the studies demonstrated any direct evidence, the consensus of the major researchers in the field at that time was that

In 1990, Heaps et al. analyzed 195 cases that mostly fulfilled Sampson's criteria (Heaps, 1990). They found that the primary endometriosis site was most frequently the ovary (78.7%), followed by various other sites such as the pelvis, rectovaginal septum, colon or rectum, or the vagina. The most frequent histologic subtype was endometrioid adenocarcinoma in either of the primary sites, ovarian (69%) or extragonadal (66%), followed by clear cell carcinoma and sarcoma in 13.5% and 11.6% of ovarian tumors, respectively, and sarcomas in 25% of extragonadal tumors. More recently, an elevated risk of ovarian cancer development in endometriosis has been shown by statistical analyses. A

prevention of endometriosis-associated ovarian cancer is necessary.

malignant transformation or transition occurred in ovarian endometriosis.

**2. Risk of cancer development in endometriosis** 

**1. Introduction** 

**The Role of Oxidative Stress** 

Yoriko Yamashita and Shinya Toyokuni *Nagoya University Graduate School of Medicine,* 
