25.44 ± 26.61 27.06 ± 23.72 25.44 ± 26.61 28.43 ± 25.18 18.83 ± 9.85 p 0.821 NS Variable VEGF Absent Present VEGF intensity Absent Low Moderate VEGF = Vascular endothelial growth factor; hCG = human chorionic gonadotropin; SD = standard deviation 1840.7 ± 4444.0 16581.0 ± 85185.0 1840.7 ± 4444.7 19337 ± 91973.8 47.35 ± 71.86 p 0.422 NS Journal of Experimental & Clinical Cancer Research 2009, 28:120 http://www.jeccr.com/content/28/1/120 Table 6: Association of VEGF expression with hCG levels and vascular density hCG median (mIU/mL) ± SD Vascular density median ± SD survival. This could be a consequence of the low recur- rence rate in our population (70% of our patients pre- sented a good international risk), making it difficult to find a statistical association. With similar results, in a study of 51 patients with stage I disease, no association was found between VD and VEGF expression and DFS [37]. Concerning these results, there is a possibility that angiogenic factors other than VEGF are relevant in the development of this neoplasm's vascularization, taking into account the fact that modulation of the angiopoietin family has been previously described in non-tumor mod- els [38,39], as well as fibroblast growth factor [40], metal- loprotease induction, and cellular adhesion-molecule expression [41]. Unexpectedly, we found no correlation between hCG serum levels and VEGF tissue expression. Our results indi- cate that hCG and VEGF may operate through different signaling pathways for angiogenesis stimulation, and sug- gest that hCG is not only an independent prognostic fac- tor, but that also it additionally plays a role in the pathophysiology of these neoplasms, representing a potential therapeutic target in patients showing signifi- cant elevations of this hormone and who display no response to treatment. Conclusion Our study shows that hCG elevation is independently associated with high VD in testicular germ cell tumors, but not with VEGF expression. This suggests that hCG plays an important function in the angiogenesis and pathophysiol- ogy of germ cell neoplasms, being a likely target of treat- ment by receptor inhibition, activity blockage, or obstruction of intracellular pathways it triggers. Competing interests The authors declare that they have no competing interests. Authors' contributions OA design and conception of the study, analysis of data, revision of the manuscript, RMM acquisition and analysis of data, draft and revision of the manuscript, JAS acquisi- tion of data, CVG critically revised the manuscript and also contributed to the analysis, AAS supervised the immunohistochemistry, revised the manuscript, JGCV checked the immunohistochemistry, revised the final ver- sion, EAO revised the data, ALG carried out the immuno- histochemistry, MAJ critical revision of the manuscript and JLA conception of the study and revision of the man- uscript. All authors have read and approved the final ver- sion of the manuscript. References 1. Bosl GJ, Motzer RJ: Testicular germ-cell cancer. N Engl J Med 1997, 337:242-254. 2. Boyle P: Testicular cancer: the challenge for cancer control. Lancet Oncol 2004, 5:56-61. 3. van Basten JP, Schrafford Koops H, Sleijfer DT, Pras E, van Driel MF, Hoekstra HJ: Current concepts about testicular cancer. Eur J Surg Oncol 1997, 23:354-360. 4. Gori S, Porrozzi S, Roila F, Gatta G, De Giorgi U, Marangolo M: Germ cell tumours of the testis. Crit Rev Oncol Hematol 2005, 53:141-164. 5. Jones RH, Vasey PA: Testicular cancer: Part 1, Management of early disease. Lancet Oncol 2003, 4:730-777. 6. Scardino PT, Cox HD, Waldmann TA, Mcintire KR, Mittenmeyer B, Javadpour N: The value of serum tumor markers in the staging and prognosis of germ cell tumors of the testis. J Urol 1977, 118(6):994-999. 7. Doherty AP, Bower M, Christmas TJ: The role of tumour mark- ers in the diagnosis and treatment of testicular germ cell cancer. Br J Urol 1997, 79(2):247-252. 8. Perkins GL, Slater ED, Sanders GK, Prichard JG: Serum tumor markers. Am Fam Physician 2003, 68(6):1075-1082. 9. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N: Vascu- lar endothelial growth factor is a secreted angiogenic mitogen. Science 1989, 246(4935):1306-1309. 10. Dvorak HF, Brown LF, Detmar M, Dvorak AM: Vascular permea- bility factor/vascular endothelial growth factor, microvascu- lar hyperpermeability and angiogenesis. Am J Pathol 1995, 146(5):1029-1039. 11. Viglietto G, Romano A, Maglione D, Rambaldi M, Paoletti I, Lago CT, Califano D, Monaco C, Mineo A, Santelli G, Manzo G, Botti G, Chiap- petta G, Persico MG: Neovascularization in human germ cell tumors correlates with a marked increase in the expression of the vascular endothelial growth factor but not the pla- centa-derived growth factor. Oncogene 1996, 13(3):577-587. 12. Fukuda S, Shirahama T, Imazono Y, Tsushima T, Ohmori H, Kayajima T, Take S, Nishiyama K, Yonezawa S, Akiba S, Akiyama S, Ohi Y: Expression of vascular endothelial growth factor in patients with testicular germ cell tumors as an indicator of meta- static disease. Cancer 1999, 85(6):1323-1330. 13. Abdallah MA, Lei ZM, Li X, Greenwold N, Nakajima ST, Jauniaux E, Rao ChV: Human fetal nongonadal tissues contain human chorionic gonadotropin/luteinizing hormone receptors. J Clin Endocrinol Metab 2004, 89(2):952-956. Page 6 of 7 (page number not for citation purposes)