**2.3 Proteins in invading process of endometrial tissue**

In endometriosis, after the attachment to the ectopic sites, the epithelial endometrial cells invade to the extracellular matrix with MMPs and TIMPs secretion playing an important role in degradation in extracellular matrix and basement membrane components [30]. It has been proved that this process is related to the involvement of MMPs, which is stimulated by TNF-a and IL-1 at high concentrations in peritoneal fluid. Meanwhile, TNF-a inhibits TIMP-1 and TIMP-2, leading to an imbalance of MMPs/TIMPs ratio. In patients of endometriosis, MMP-2 and membranous type 1 of eutopic endometrium have been found higher, TIMP-2 was lower than normal women [31]. Increased MT5- MMP expression and alterations of the balances between MMP-9/TIMP-1, MMP-9/TIMP-3, MMP-3/uPA, VEGF/MMP-3/uPA, VEGF/ /MMP-2/CD44/Ki67, PAI/TIMP-1, and IL-1/ /MMP-1 indicated that implantation and invasion might participate the mechanism of endometriosis [32–38].

## **2.4 Proteins in carcinogenesis possibility of endometriosis**

Clinicopathological, molecular, and genetic evidences support the hypothesis of endometriosis as a neoplastic process, with a potential to malignant transformation. Polypoid endometriosis, premalignant changes, borderline tumors and malignant tumors were described. Except for an increased MMPs expression associated to deregulation of the intercellular adherence signaling, tumor suppressor genes, oncogenes, CAMs, furthermore LOH and inflammatory immunomodulation were detected [39, 40]. The progressive accumulations of genetic alterations of tumorsuppressing genes and oncogenes are probably responsible for endometriosis development and its possible association with the development of malignancies [41–45].
