T19: The immune and vascular components of microenvironment in prognosis of the endometrioid endometrial adenocarcinoma

Abstract

Background Endometrioid endometrial adenocarcimoma is the most frequent gynecologic malignancy in the western world. It is well known that inflammation plays a key role in the initiation and development of cancer as well as promotes both specific and innate immune response. There is no information on the status of the local anti-tumor cellular immunity in endometrioid adenocarcinoma of the corpus uteri microenvironment in the Russian and English language medical scientific literature. Various studies have shown that high intratumor microvessel density in endometrial cancer is associated with advanced stage, increased risk of recurrent disease and with poor prognosis. Vascular endothelial growth factor (VEGF) is a glycoprotein with potent mitogenic activity. It has been demonstrated to be a key component in the promotion of angiogenesis. Materials and methods There were singlet 24 cases of endometrioid adenocarcinoma with retrospectively known good (survival) and poor (death) outcomes. All cases were immunohistochemically stained for CD3, CD20, CD57, CD68, S100, CD34 and VEGF, expression of was evaluated by IHC-profiler. The number and the area of vessels was count in “hot spot” zones and calculated per 1 mm. For compare of the characteristics of signs was used comparison of two independent samples – U-Mann–Whitney test. The level of statistical significance was accepted by p Results T-lymphocytes cells were situated predominantly in desmoplastic stroma of the tumor. CD3 expression was significant higher in the group of good outcome (p = 0.00042), B-lymphocytes cells were predominantly in epithelial component of tumor. CD20 was expressed in endometriod adenocarcinoma with good and poor outcome without statistically significant difference (p = 0.976). NK-lymphocytes were predominantly in peritumoral stroma. CD57 expression was statistically significant higher in the group of good outcome (p = 0.000307). Tumor infiltrating macrophages can were frequent in tumor stroma than in tumor islets. CD68 expression cells number was higher in the group with good outcome (p = 0.000219). Dendric cells were predominantly in epithelial component of tumor. S100+ cells number did not have any difference (p = 0.105). Inside the tumor stroma, among pseudo-glands or solid beaches there was a positive reaction for anti-CD34 of numerous microvessels together with groups of endothelial cells (“hot spot”). The number of intratumoral vessels in patients with poor outcome was 141.9 ± 24.7 vessels/mm2, in good outcome patients – 93.8 ± 28.7 vessels/mm2. The number of the intratumoral vessels in this groups was with significant statistical different (p = 0.0014). The area of intratumoral vessels in good outcome cases was 2799.7 ± 535.7 μm2, poor outcome cases – 5455,2 ± 448,8 μm2. It was significant statistical different (p = 0.000014). VEGF was expressed in the cytoplasm of normal endometrial cells, neoplastic ones, endothelial cells and stroma. VEGF represents a mitogen for endothelial cells that induces the formation of lumen’s vessels and also increases vascular permeability and protein extravasation. Expression of VEGF by cancer cells had significant statistical difference in this groups of patients (p = 0.0411). Conclusion There was a significant reduction in T, NK-cells and macrophages from patients with poor outcome indicates the development of local immune deficiency that could certainly plays an important role in tumor progression endometrioid carcinoma. Our study demonstrates that the number and the area of vessels, as part of angiogenesis, represent an important prognostic factor in outcome of endometrioid endometrial adenocarcinoma. VEGF expression also is an angiogenic factor which plays a great role in the prognosis of this tumor.