Vascular markers CD31, CD34, actin, VEGFB, and VEGFR2, are prognostic markers for malignant development in benign endometrial polyps

Abstract

Intention of the study: The prevalence of endometrial polyps has been demonstrated in between 10% and 35% of all women, but knowledge regarding malignant potential within polyps is limited. Even though premalignant and malignant changes have been reported in up to 24% of all cases, no objective tissue markers have ever been developed for routine diagnostics to select high risk cases. As vascular changes and activation of endometrial angiogenesis has been demonstrated in former studies, our main objective was to evaluate different members of the angiogenic pathway as potential risk factors for cancer development. Patients and methods: Formalin-fixed, paraffin-embedded tissue from 15 women with benign endometrial polyps, and 16 women diagnosed with endometrial cancer were included. Immunohistochemical investigation with antibodies against VEGF, VEGF-B, VEGFR2, VEGFR3, CD31, CD34, actin, and factorVIII was performed, followed by evaluation of staining intensity of microvessels, evaluation of H-score in glands (cell membrane, cytoplasm) and stroma, and measurement of micro vessel density. Results: Expression of CD31 in microvessels was significantly stronger in cancers compared to endometrial polyps (P = 0.006 for arterioles, P = 0.038, for venyles, and P = 0.002 for capillaries, respectively), whereas, a reverse change was shown for CD34. Expression of actin in capillary walls was also significantly increased in cancers compared to polyps (P = 0.002). No significant difference was found for staining intensity in microvessels (arterioles, venyles or capillaries) in endometrial benign polyps compared with endometrial cancers for VEGF, VEGFB, VEGFR2, VEGFR3, or Factor VIII. Also no difference in H-score values between benign polyps and endometrial cancers could be detected in glandular epithelium, in epithelial cell membrane or in stroma for VEGFR3, CD31 or Factor VIII. Conclusions: The present study strongly indicates that activation of angiogenesis differs in benign endometrial polyps and endometrial cancers. Thus, immunohistochemical expression of specific angiogenic markers may be of great importance as prognostic factors in the routine diagnostics of this lesion. The ratio between stromal expression of CD34 and actin might be of particular interest to select polyps with increased malignant potential.