Abstract

PurposeOne of the most important function of stromal derived factor-1 (SDF-1) and its receptors, is regulating the process of metastasis formation. The aim of our study was to investigate the correlation between SDF-1, CXCR4 and CXCR7 protein levels measured by immunohistochemistry with the clinicopathological features and the survival of endometrial cancer patients.Materials and Methods92 patients aged 37–84 (mean 65.1±9.5) were enrolled to our study between January 2000 and December 2007. After the diagnosis of endometrial cancer, all women underwent total abdominal hysterectomy, with bilateral salpingoophorectomy and pelvic lymph node dissection. In all patients clinical stage (according to FIGO classification), histologic grade, myometrial invasion, lymph node and distant metastases were determined.Furthermore, the survival time was assessed. Immunohistochemical analyses of SDF-1, CXCR4 and CXCR7 were performed on archive formalin fixed paraffin embedded tissue sections.ResultsStatistically significant correlations (p<0.01) were reported between SDF-1 and the clinical stage of disease, lymph node metastases, distant metastases, deep myometrial invasion (≥50%), cervical involvement, involvement of adnexa. Statistically significant correlation (p<0.01) was found between SDF-1 expression and the risk of the recurrence. Higher SDF-1 expression was associated with ahigher risk of recurrence (p = 0.0001). The results of CXCR4and CXCR7 expression didn't reveal any significant differences(p>0.05) between the proteins expression in the primary tumor cells and the clinicopathological features. Moreover, the Kaplan-Meier analyses demonstrated a stepwise impairment of cancer overall survival (OS) with increasing SDF-1 expression.ConclusionThe important role of SDF-1 as a predictor of negative clinicopathological characteristics of atumor suggests that the expression of this stromal factor should be included in the panel of accessory pathomorphological tests and could be helpful in establishing a more accurate prognosis in endometrial cancer patients.

Highlights

  • Conditions in which tumor cells are able to initiate local or distant spreadare very important but still unknown clinical issue

  • The Kaplan-Meier analyses demonstrated a stepwise impairment of cancer overall survival (OS) with increasing stromal derived factor-1 (SDF-1) expression

  • The purpose of our study was to investigate the correlation between SDF-1, CXCR4 and CXCR7 protein levels measured by immunohistochemistry with theclinicopathological features and survival of endometrial cancer patients

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Summary

Introduction

Conditions in which tumor cells are able to initiate local or distant spreadare very important but still unknown clinical issue. Tumor growth and ability to initiate metastases are connected with the continuous interaction between cancer cells and the host’s microenvironment. The tumor microenvironment plays an important role in each step of cancer development. There is continuous interaction between cancer cells and extracellular matrix (ECM), with fibroblasts, endothelial cells and inflammatory cells [1]. Several studies have indicated that the tumor microenvironment responds to factors derived from the tumor cells, as well as vice versa and in consequence has an impact on the neoplastic transformation[2]. The microenvironment could be involved in promoting the mutagenesis of tumor cells as well as in modification of the tumor stroma compartment. Neoplastictransformationleads to phenotypicmodifications in stromalcells[3],[4]

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