Jayson Wang1, Alexandra Taylor2, Rania Showeil3, Pritesh Trivedi4, Yoshiya Horimoto5, Izhar Bagwan6, Lauren Ewington7, Eric W-F Lam8, Mona A El-Bahrawy9. 1. Department of Histopathology, Imperial College London, UK. Electronic address: jayson.wang@imperial.ac.uk. 2. Department of Gynaecology, Royal Marsden Hospital, UK. Electronic address: Alexandra.Taylor@rmh.nhs.uk. 3. Department of Histopathology, Imperial College London, UK. Electronic address: raniashoweil@yahoo.com. 4. Department of Histopathology, Imperial College London, UK. Electronic address: Pritesh.Trivedi@imperial.nhs.uk. 5. Department of Oncology, Imperial College London, UK. Electronic address: yoshiyahorimoto@hotmail.com. 6. Department of Histopathology, Royal Surrey County Hospital, Guildford, UK. Electronic address: izhar_dr@yahoo.com. 7. Department of Histopathology, Imperial College London, UK. Electronic address: Lauren.Ewington@imperial.ac.uk. 8. Department of Oncology, Imperial College London, UK. Electronic address: eric.lam@imperial.ac.uk. 9. Department of Histopathology, Imperial College London, UK; Department of Pathology, Faculty of Medicine, University of Alexandria, Egypt. Electronic address: m.elbahrawy@imperial.ac.uk.
Abstract
BACKGROUND: Angiogenesis plays a key role in the progression of various tumors, including endometrial carcinomas. Several cytokines and their associated receptors are shown to be involved, particularly VEGF-A with VEGFR1, -2 and -3. METHODS: The expressions of VEGF-A, VEGFR2 and VEGFR3 were studied in by immunohistochemistry in 76 endometrial carcinoma specimens. VEGFR2 and VEGFR3 receptor expression were also studied by qRT-PCR in 17 tumors in comparison to normal endometrium. The expression profiles were correlated with tumor type, grade, stage, lymphovascular invasion, disease free survival, and the expressions of other cytokine receptors (EGFR, CXCR1 and CXCR2). RESULTS: Immunohistochemically, 63% of endometrial cancers expressed VEGF-A, 55% VEGFR2 and 26% VEGFR3. VEGFR3 was significantly correlated with tumor stage (p=0.02), with a trend towards poorer disease free survival (p=0.09). VEGF-A was significantly correlated with microvessel density (p<0.01). Using qRT-PCR, increased expression of VEGFR2 (17.2-fold) and VEGFR3 (21.9-fold) was seen in endometrial carcinomas compared with normal endometrium, with significant correlations among the expression levels of VEGFR2, VEGFR3, EGFR, CXCR1 and CXCR2. CONCLUSION: Our study suggests that evaluation of VEGFR3 expression in tumors may provide prognostic data, and help identify patients who would best benefit from anti-angiogenic therapeutic agents. This is the first report showing correlations between the expressions levels of the different receptors.
BACKGROUND: Angiogenesis plays a key role in the progression of various tumors, including endometrial carcinomas. Several cytokines and their associated receptors are shown to be involved, particularly VEGF-A with VEGFR1, -2 and -3. METHODS: The expressions of VEGF-A, VEGFR2 and VEGFR3 were studied in by immunohistochemistry in 76 endometrial carcinoma specimens. VEGFR2 and VEGFR3 receptor expression were also studied by qRT-PCR in 17 tumors in comparison to normal endometrium. The expression profiles were correlated with tumor type, grade, stage, lymphovascular invasion, disease free survival, and the expressions of other cytokine receptors (EGFR, CXCR1 and CXCR2). RESULTS: Immunohistochemically, 63% of endometrial cancers expressed VEGF-A, 55% VEGFR2 and 26% VEGFR3. VEGFR3 was significantly correlated with tumor stage (p=0.02), with a trend towards poorer disease free survival (p=0.09). VEGF-A was significantly correlated with microvessel density (p<0.01). Using qRT-PCR, increased expression of VEGFR2 (17.2-fold) and VEGFR3 (21.9-fold) was seen in endometrial carcinomas compared with normal endometrium, with significant correlations among the expression levels of VEGFR2, VEGFR3, EGFR, CXCR1 and CXCR2. CONCLUSION: Our study suggests that evaluation of VEGFR3 expression in tumors may provide prognostic data, and help identify patients who would best benefit from anti-angiogenic therapeutic agents. This is the first report showing correlations between the expressions levels of the different receptors.
Authors: Neesha C Dhani; Hal W Hirte; Lisa Wang; Julia V Burnier; Angela Jain; Marcus O Butler; Stephen Welch; Gini F Fleming; Jean Hurteau; Koji Matsuo; Daniela Matei; Waldo Jimenez; Carolyn Johnston; Mihaela Cristea; Katia Tonkin; Prafull Ghatage; Stephanie Lheureux; Anjali Mehta; Judy Quintos; Qian Tan; Suzanne Kamel-Reid; Olga Ludkovski; Ming-Sound Tsao; John J Wright; Amit M Oza Journal: Clin Cancer Res Date: 2020-01-28 Impact factor: 12.531