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OBJECTIVE To study the mechanisms of invasion and innervation of deep endometriosis in women. DESIGN Morphologic and immunohistochemical analysis of human endometriotic lesions. SETTING Academic research unit. PATIENT(S) Seventeen biopsy samples of deep endometriotic lesions were collected from patients undergoing surgery for deep endometriosis. INTERVENTION(S) The endometriotic samples were divided into two parts: the front (the most invasive area of lesions, approaching rectal infiltration) and center (the area close to the posterior part of the cervix). MAIN OUTCOME(S) To elucidate: gland morphology, proliferation, and expression of adhesion molecules (β-catenin, E-cadherin, and N-cadherin) to determine the possible role of collective cell migration (CCM) in the invasion process; and nerve growth factor (NGF) and nerve fiber density (NFD) values to shed further light on the mechanism of innervation. RESULTS Glands from the front showed significantly reduced thickness, but significantly higher proliferation. β-Catenin expression was similar between the lesion center and front. E-cadherin levels were significantly lower and N-cadherin levels significantly higher in glands located at the front of the lesions. Expression of matrix metalloproteinase-9 was significantly higher in glands and stromal cells located at the invasion front. NFD and NGF expression were also significantly higher at the lesion front. CONCLUSION Although some data in the literature point to features of epithelial to mesenchymal transition in human deep nodular endometriosis, our study suggests that gland invasion in these lesions is dominated by CCM. Innervation of deep nodular endometriotic lesions may be a consequence of nerve recruitment from surrounding organs.