RESUMO
Endometrial cancer (EC) is the most frequently observed malignant gynecologic disease in developed countries. There is a strong association between the established risk factor obesity and the incidence of EC. Furthermore, the rate of women with a body mass index (BMI) > 30 kg/m2 is increasing worldwide, correspondingly leading to a higher prevalence of EC. Understanding the adipose tissue as an endocrine organ, elementary pathophysiological pathways of tumorigenesis have been revealed. This includes the fundamental role of hyperglycemia, insulin resistance, and hyperestrogenemia, as well as interactions with a chronic proinflammatory microenvironment. Therapeutic options potentially include metformin or bariatric surgery. Moreover, changes in individual lifestyle such as weight reduction, physical activity, and an awareness of healthy nutrition are effective in preventing the disease.
RESUMO
Aminopeptidase N (CD13) is expressed on tumor vasculature and tumor cells. It represents a candidate for targeted therapy, e.g., by truncated tissue factor (tTF)-NGR, binding to CD13, and causing tumor vascular thrombosis. We analyzed CD13 expression by immunohistochemistry in 97 patients with STS who were treated by wide resection and uniform chemo-radio-chemotherapy. Using a semiquantitative score with four intensity levels, CD13 was expressed by tumor vasculature, or tumor cells, or both (composite value, intensity scores 1-3) in 93.9% of the STS. In 49.5% tumor cells, in 48.5% vascular/perivascular cells, and in 58.8%, composite value showed strong intensity score 3 staining. Leiomyosarcoma and synovial sarcoma showed low expression; fibrosarcoma and undifferentiated pleomorphic sarcoma showed high expression. We found a significant prognostic impact of CD13, as high expression in tumor cells or vascular/perivascular cells correlated with better relapse-free survival and overall survival. CD13 retained prognostic significance in multivariable analyses. Systemic tTF-NGR resulted in significant growth reduction of CD13-positive human HT1080 sarcoma cell line xenografts. Our results recommend further investigation of tTF-NGR in STS patients. CD13 might be a suitable predictive biomarker for patient selection.