Multiple pregnancies, childbirth, induced abortion, chronic endometritis and other factors make the endometrial basal layer thinning and loss of protective function. The endometrium grows through direct contact with the myometrium through the unprotected areas and invades the myometrium, and further invades the surrounding tissue. In the observation of pathological sections of AM patients undergoing hysterectomy, endometrial glands and stromal tissues were found in 10–47% of the myometrium, which were closely connected with the endometrium. Therefore, although AM is a benign pathological manifestation, it has biological characteristics similar to malignant tumors, such as implantation, growth, infiltration, recurrence and so on. In addition to the basement membrane invagination theory, the pathogenesis of AM may be related to estrogen metabolism disorder, EMT, eutopic endometrial lesion, immune factors and genetic factors. From the perspective of EMT, exploring the pathogenesis of AM will become an important research direction in the future. Research finds promotion for the growth, distant metastasis and angiogenesis of AM endometrial tissue is implemented through the mechanism on ANXA2-inducing EMT [
5]. ANXA2 was first discovered in 1979 by Rade and Martin. Its basic structure contains 339 amino acids, consisting of the N-terminal of 3 kD and the C-terminal domain of 33 kD. As a calcium-binding cytoskeleton protein, it has many functions including angiogenesis, proliferation, apoptosis, calcium signal transduction and cell growth regulation [
7‐
9]. The mechanism on induction EMT in AM may be through binding fibrinogen then hydrolyzing to fibrinolysis enzyme, which can degrade extracellular matrix and peripheral vascular basement membrane [
14]. It is possible to change cell-to-cell and cell-to-matrix adhesion by binding to cell surface adhesion molecules to enhance the anti-apoptosis and motility of cells, and then induce epithelial-to-mesenchymal cell transformation (EMT) [
3,
4]. Research finds that ANXA2 abnormal expression in cervical cancer, ovarian cancer, choriocarcinoma and other gynecological malignancies [
15] and AM also has biological behavior similar to a malignant tumor. According to ANXA2 function and the above in vitro study AM, the mechanism is speculated. In the human body of AM, that ANXA2 abnormal expression probably promoted the occurrence and development of AM have not been reported. In this study, the expression of ANXA2 in AM was detected by immunohistochemistry S-P method. There was no significant difference between the two groups (
P > 0.05), but the expression was higher in eutopic endometrium and ectopic endometrium than in normal endometrium (
P < 0.05). In vitro studies found that the increased expression about ANXA2 in AM ectopic lesions was consistent [
5]. This not only confirms the abnormal expression of ANXA2 in human AM tissues, but also indicates that the effect of ANXA2 in AM epitope and ectopic endometrium may be the same, and may be different from that in uterine leiomyoma. It indicates that ANXA2 may play an important role in the development of AM.
Progressive dysmenorrhea is the main clinical manifestation of AM, seriously affecting the quality of life of patients, some patients just because of dysmenorrhea can not bear the reluctance to remove the uterus. It is reported that the dysmenorrhea rate of AM patients is as high as 64.8–77.8% [
16]. It is noted that dysmenorrhea is closely related not only to estrogen but also to prostaglandins and cyclooxygenases 2. A study confirmed that estrogen significantly up-regulates ANXA2 [
5]. Another study found that prostaglandin E2 increased significantly in uterine tissues of AM patients, especially in patients with severe dysmenorrhea. Cyclooxygenase 2 is the rate-limiting enzyme for the conversion of arachidonic acid to prostaglandins. It was observed that ANXA2 significantly increased the expression of Cyclooxygenase 2 in peritoneal macrophages of patients with endometriosis by PCR and Western-blot methods [
17]. It can be seen that AM-elevated estrogen levels in patients may increase cyclooxygenase 2 by up-regulating ANXA2. There by increasing prostaglandin E2 production and promoting dysmenorrhea. EMT is strongly related to high estrogen environment. Estrogen-induced EMT is one of the important mechanisms of AM development. Among them, ANXA2 may play a key role. The relationship between ANXA2 expression and dysmenorrhea in AM tissues was tested in this study. The expression level of ANXA2 in AM ectopic endometrium was positively correlated with dysmenorrhea degree (
R = 0.831,
P = 0.000). The expression level of ANXA2 in AM ectopic endometrium increased gradually with the degree of dysmenorrhea. These results suggest that the exacerbation of dysmenorrhea is closely related to the up-regulation of ANXA2 expression in AM lesions, and there is a certain correlation between them. It is suggested that ANXA2 is involved in the occurrence of AM and dysmenorrhea, and promotes the development of AM and the aggravation of dysmenorrhea.
Preoperative diagnostic coincidence rate of AM by ultrasonography was only 52.9–60.5% and misdiagnosis rate was high. Preoperative diagnostic coincidence rate of MRI was 88.2%, but the high price limited the clinical application. Although the detection of serum CA125 has some reference value in the diagnosis of AM, the positive rate and the value of serum CA125 have not been reported in the literature. There is still a lack of sensitivity and specificity, so it is necessary to develop more reliable markers. In this study, the serum concentration of ANXA2 in AM patients was determined by ELISA for the first time, which was significantly higher than that in hysteromyoma patients (P < 0.05), suggesting that ANXA2 might be a new marker for the diagnosis of AM. Gene-targeting therapy for ANXA2, a biological target, provides a new therapeutic approach to alleviate dysmenorrhea in AM patients and to meet the conservative and fertility requirements of some patients after the open second-child policy.