**4. Microsatellite Instability (MSI)**

140 Endometriosis - Basic Concepts and Current Research Trends

hydroxysteroid dehydrogenase type 1 (HSD17B1). Evidence for association between the Ser312Gly polymorphism in HSD17B1 and endometriosis was found in a Japanese population. The A-allele of HSD17B1 appears to confer higher risk for endometriosis

The *Alu*I polymorphism in the ERβ gene is associated with an increased risk of stage IV endometriosis in a Japanese population (Wang Z et al, 2004).The *Pvu*II polymorphism of the ERα gene is associated with the risk for endometriosis, adenomyosis and leiomyomata in Japanese women (Kitawaki J et al, 2001). The ERα dinucleotide repeat and cytochrome P450c17α gene polymorphisms are associated with susceptibility to endometriosis in

Androgen receptor gene is present in the endometrial tissue and the pelvic organs, which are the targets for endometriotic implants. The AR was detected in endometriosis, adenomyosis and endometrial carcinoma (Horie K et al 1992). Endometrial cysts are monoclonal in origin and are related to the reaction with AR. The endometrioma might be formed from an independent monoclonal ovarian endometrial cell after inactivation of AR allele in the X chromosome (Fujimoto J et al, 1999). The proliferation and differentiation of the endometrium are mediated mainly by the Estrogen and Progesterone receptors. However, Androgen receptor also plays a role in modulating the cyclic change of the

*Androgen Receptor (AR) gene* trinucleotide polymorphism has been associated with endometriosis (Yao-Yuan-Hsieh et al, 2001). The AR gene has a polymorphic cytosine, adenine and guanine (CAG) microsatellite in exon 1 that codes for variable length glutamine repeats in the amino-terminal domain of the AR protein (Hsieh.Y Y et al, 2004). The 21-CAG repeats may be associated with some determinants for endometriosis formation as indicated

Estrogen and progesterone receptors are present in the ectopic endometrium but in lower concentrations than in eutopic endometrium. Cyclical variation in the receptor population has not been observed and also there seems to be a difference in the way that estrogen is

The expression of the variants of the Progesterone Receptor (PR-A and PR-B) was shown to be aberrant in endometriotic tissues, which may indicate a role of the progesterone receptor

The progesterone receptor gene is located in chromosome region 11q22-23.PROGINS polymorphism has been studied in association with breast cancer (Wang-Gohrke S et al, 2000) and ovarian cancer (Vigano P et al, 2006). The data indicate that a mutated progesterone

*Progesterone Receptor (PR) gene PROGINS* polymorphism has been shown to be associated with endometriosis in Caucasian women (Weiser F et al, 2002). The secretory phase of the

(Tsuchia M et al, 2005).

Taiwanese women (Hsieh.Y Y et al, 2005).

in a study by Lattuada et al, (2004) in Italian women.

handled by the endometrium at the two sites (Vierikko P et al, 1985).

in the pathogenesis of endometriosis (Nisolle M et al, 1994; Attia GR et al 2000).

receptor gene contributes to the development of disease in hormone-sensitive tissues

**3.3.3 Progesterone Receptor (PR)** 

**3.3.2 Androgen Receptor (AR)** 

endometrium.

Microsatellites are short sequence elements that consist of mononucleotide to hexanucleotide motifs reiterated several times. This form of genomic instability is caused by defects in the DNA mismatch repair system. Genomic instability is an almost universal feature of cancer cells. Microsatellite instability is a DNA level instability seen in a number of tumors, including colon cancers. Instability is probably necessary to enable a cell to amass enough mutations and is not a chance feature, but is the result of selection. High frequency of MSI is defined as >29% of all markers and are defined as a class of MSI positive tumors (Strachanan & Read 2004).

### **4.1 Microsatellite (MS) markers**

Genetic alterations in microsatellite marker sites among eight tumor suppressor genes in endometriosis were examined and reported that MSI is not ubiquitous in endometriosis and may be uncommon (Nakayama K et al, 2001). MSI assays reveal an allelic imbalance and loss of heterozygosity (LOH) on p16(Ink4), GALT, p53, APOA2 loci in endometriosis. The 9p21 locus may be a prognostic marker of the disease (Goumenou AG et al, 2001).
