Specific Local Predictors That Reflect the Tropism of Endometriosis—A Multiple Immunohistochemistry Technique

Abstract

Ectopic endometrial epithelium associates a wide spectrum of symptomatology. Their evolution can be influenced by inflammatory and vascular changes, that affect not only the structure and cell proliferation rate, but also symptoms. This prospective study involved tissue samples from surgically treated patients, stained using classical histotechniques and immunohistochemistry. We assessed ectopic endometrial glands (CK7+, CK20−), adjacent blood vessels (CD34+), estrogen/progesterone hormone receptors (ER+, PR+), inflammatory cells (CD3+, CD20+, CD68+, Tryptase+), rate of inflammatory cells (Ki67+) and oncoproteins (BCL2+, PTEN+, p53+) involved in the development of endometriosis/adenomyosis. A CK7+/CK20− expression profile was present in the ectopic epithelium and differentiated it from digestive metastases. ER+/PR+ were present in all cases analyzed. We found an increased vascularity (CD34+) in the areas with abdominal endometriosis and CD3+−:T-lymphocytes, CD20+−:B-lymphocytes, CD68+:macrophages, and Tryptase+: mastocytes were abundant, especially in cases with adenomyosis as a marker of proinflammatory microenvironment. In addition, we found a significantly higher division index-(Ki67+) in the areas with adenomyosis, and inactivation of tumor suppressor genes-p53+ in areas with neoplastic changes. The inflammatory/vascular/hormonal mechanisms trigger endometriosis progression and neoplastic changes increasing local pain. Furthermore, they may represent future therapeutic targets. Simultaneous-multiple immunohistochemical labelling represents a valuable technique for rapidly detecting cellular features that facilitate comparative analysis of the studied predictors.

Clinical Characteristics and Local Histopathological Modulators of Endometriosis and Its Progression

“…Malignant degeneration may occur under the influence of local inflammatory, vascular or hormonal factors that contribute to the development of atypical hyperplastic and subsequently malignant lesions. The malignant aspect must be carefully distinguished when there are deep infiltrating nodules or intracystic papillary projections [14]. E and A are not malignant disorders, but some characteristics are similar to cancer: they can develop local and distant foci, develop resistance to apoptosis and invade other tissues with subsequent damage [15].…”

“…Histopathological examination is the mainstay for the final diagnosis of E or A and the extent of tissue proliferation. Classical histological staining, hematoxylin-eosin (HE), highlights endometrial glandular structures, the presence of peri-glandular stroma and the degree of atypical glandular transformation [14].…”

“…Immunohistochemical studies can highlight the progressive potential of E or A foci; the presence of an inflammatory microenvironment, neovascularization or hormonal receptors; or the involvement of tumor proteins in the preneoplastic or malignant transformation of E lesions [14].…”

“…The diagnosis of malignant lesions is established following clinical suspicion and histopathological confirmation by identifying the primary structures affected by E or A, the malignant process and the benign-malignant tumor transition zone. The differential diagnosis is made in the absence of other neoplasms with secondary findings [14,25].…”

Molecular and Cellular Advances in Endometriosis Research: Paving the Way for Future Directions

“…In addition, to differentiate between ectopic and eutopic endometrium, it is of paramount importance to obtain additional knowledge of the different types of endometriosis (peritoneal superficial endometriosis, ovarian endometriomas, and deep infiltrating endometriosis); in this context, an interesting study shed new lights on this topic, remarking how different phenotypes of endometriosis show an altered differential expression of genes and microRNAs in relation to adhesion and apoptosis pathways [ 4 ]. In addition, Istrate-Ofiţeru et al found increased vascularity (CD34+) in areas with abdominal endometriosis and CD3+-:T-lymphocytes, CD20+-:B-lymphocytes, CD68+:macrophages, and Tryptase+: mastocytes were abundant, especially in cases with adenomyosis as a marker of the proinflammatory microenvironment, and a significantly higher division index-(Ki67+) in areas with adenomyosis, and the inactivation of tumor suppressor genes-p53+ in areas with neoplastic changes [ 5 ].…”