**1. Introduction**

Endometriosis is a benign gynaecological disease characterized by the presence of endometrial glands and stroma outside the uterine cavity. This condition is mainly found in women of reproductive age, from all ethnic and social groups and it is associated with pelvic pain and infertility. Endometriosis is typically present in the pelvis such as on the ovaries and pelvic peritoneum, but may also involve the bowel, ureter or bladder. It regresses after menopause or ovariectomy, suggesting it could depend on the production and metabolism of sex steroids: high concentrations of estrogens were found in the endometriotic lesions, which grow and regress in an oestrogen-dependent way. Nevertheless, the pathogenesis and the molecular mechanism that underlie the development of endometriosis have troubled the investigators through many years, remaining an enigma. The disease is widely accepted to result from the ectopic implantation of refluxed menstrual tissues. In addition, immunologic changes, environmental, hormonal and genetic factors contribute to the multifactorial etiology of endometriosis.

Many studies are therefore focusing on identifying markers for the diagnosis and follow-up of endometriosis. Although the ''gold standard" for the diagnosis of endometriosis is the laparoscopy, many reports have suggested that various serum, peritoneal fluid and tissue markers might be associated with endometriosis. In fact, the identification of more sensitive and specific markers of endometriosis should facilitate the development of accurate and non-invasive techniques for diagnosis and prognosis (Table 1). Furthermore, the inheritable susceptibility to endometriosis justifies the growing interest in identifying genes and/or genetic polymorphisms that could lead to an increased risk of disease. Identifying these polymorphisms may open to their use as genetic biomarkers of endometriosis.

Over the last 20 years, several proteomics technologies have been used to research novel proteins with a potential etiological role in endometriosis, and to identify candidate serum markers for this condition. While some molecules identified by proteomics technologies may have a relevant role in the pathogenesis of endometriosis, the research of potential serum markers for this condition is still far from any clinical application.

The early diagnosis of endometriosis could prevent the possible progression of endometriosis, resulting in more pain, infertility and in a declining quality of life.

Current Insights and Future Advances in Endometriosis Diagnostics 421

Progesterone Estradiol

Leptin

E-cadherin

SOLUBLE ADHESION MOLECULES Intercellular adhesions molecule-1 (sICAM-1)

Table 2. Peritoneal fluid (PF) and/or serum markers for endometriosis. (Continuation)

Some serum glycoproteins, more commonly known for its use in the diagnosis or monitoring of cancers, might also serve as a marker for endometriosis, although levels are usually elevated only in advanced stages and are therefore not suitable for routine

CA125 is a 200,000 Da glycoprotein expressed on the surface of the coelomic epithelium, including the epithelium of the endocervix, endometrium, fallopian tube, pelvic peritoneum and placental tissues. Serum CA125 levels increase in patients with malignant and benign

Despite the most important clinical use of CA125 is the monitoring of patients with ovarian cancer, high levels can be found in women with endometriosis. Many studies have assessed the role of CA125 serum levels in women affected with endometriosis. The sensitivity and specificity of serum CA125 assay varies with the stage of disease. Usually, high CA125 serum levels can be found both in most patients with advanced endometriosis and in few patients with early-stage disease. Therefore, the routine use of serum CA125 cannot be used as a diagnostic tool for endometriosis. Serum CA125 may be more useful in evaluating recurrent disease or the outcome of a surgical treatment. CA125 levels may also be useful in patients with advanced endometriosis and several studies have suggested the use of this

The patients with endometriosis often undergo repeated laparoscopic examinations to assess the progress during and after therapy or to determine the recurrence of disease. Therefore, CA125 may be useful in the management of endometriosis and some authors

Autoantibodies to oxidized lipoproteins

Thyroid stimulating hormone (TSH) Follicle stimulating hormone (FSH)

Matrix metalloproteinases (MMPs) Tissue inhibitors for MMPs (TIMPs)

Human leukocyte class I antigens (sHLA-I)

Thyroid peroxidase antibodies IgG anti-laminin-1 antibodies Anti-phospholipid antibodies

AUTOANTIBODIES Antiendometrial antibodies

HORMONES Luteinizing hormone (LH)

ENVIRONMENTAL CONTAMINAT Dioxin-like chemicals

gynaecologic diseases, including endometriosis.

marker in the preoperative diagnosis of endometriosis.

PROTEOLYTIC ENZYMES AND

THEIR INHIBITORS

**2.1 Glycoproteins** 

screening.

**2.1.1 CA125** 

For a clinical purpose, the identification of highly sensitive and specific diagnostic test of endometriosis should facilitate the development of accurate and non-invasive test diagnosis and prognosis.


Table 1. Markers for endometriosis
