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Concentrations of Alpha-Fetoprotein, Insulin-Like Growth Factor Binding Protein-3, c-erbB-2, and Epidermal Growth Factor in Serum of Patients With Endometriosis

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The Journal of the Society for Gynecologic Investigation: JSGI Aims and scope Submit manuscript

Abstract

Objective

Endometriosis, although it is a benign disorder, shares many similarities with cancer. There is increasing levels of evidence suggesting that some circulating factors involved in gynecologic cancers, such as alpha-fetoprotein (AFP), insulin-like growth factor binding protein-3 (IGFBP-3), c-erbB-2 (HER-2/ neu), and epidermal growth factor (EGF), could also play a role in endometriosis. Hence, the present study was aimed at evaluating whether the levels of these molecules are modulated in the serum of patients with endometriosis.

Methods

Levels of AFP, IGFBP-3, c-erbB-2, and EGF were determined by enzyme-linked immunosorbent assay in serum from 36 subjects with surgically confirmed endometriosis and 36 controls with no surgical evidence of the disease. In addition, information such as demographic characteristics, personal habits, menstrual characteristics, and clinical profile was collected from each participating subject.

Results

No significant difference was found between serum levels of AFP, IGFBP-3, c-erbB-2, and EGF in patients with endometriosis and controls, even when we adjusted for potential confounders and took into account the menstrual cycle. Moreover, no correlation was observed between the serum concentrations of these molecules and the stage of the disease. However, a correlation was detected between soluble levels of IGFBP-3 and presence of uterine leiomyoma.

Conclusion

Although AFP, IGFBP-3, c-erbB-2, and EGF are not altered in the circulation of patients with endometriosis, their involvement in the development of endometriotic lesions cannot be excluded, (J Soc Gynecol Investig 2004; 11:115-81)

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References

  1. Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am 1997;24:235–58.

    Article  CAS  PubMed  Google Scholar 

  2. Sampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 1927;14:422–69.

    Google Scholar 

  3. Gosselin D, Shazand K, Miron P, Lavoie HB, Domin M, Hugo P. Insights into the physiopathology of endometriosis—novel diagnostic and therapeutic approaches. Curr Opin Oncol Endo Metab Invest Drugs 1999;1:31–43.

    Google Scholar 

  4. Swiersz LM. Role of endometriosis in cancer and tumor development. Ann N Y Acad Sci 2002;955:281–92.

    Article  PubMed  Google Scholar 

  5. Sarcione EJ, Biddle W. Elevated serum alpha fetoprotein levels in postmenopausal women with primary breast carcinoma. Dis Markers 1987;5:75–9.

    CAS  PubMed  Google Scholar 

  6. Motawy MS, Szymendera JJ, Al-Jazzaf H, et al. Serum AFP, hCG and CEA in the management of patients with testicular, ovarian and extragonadal germ cell tumors. Int J Biol Markers 1992;7:80–6.

    Article  CAS  PubMed  Google Scholar 

  7. Sell A, Sogaard H, Norgaard-Pedersen B. Serum alpha-fetoprotein as a marker for the effect of post-operative radiation therapy and/or chemotherapy in eight cases of ovarian endodermal sinus tumour. Int J Cancer 1976;18:574–80.

    Article  CAS  PubMed  Google Scholar 

  8. Koyama Y, Taketa K, Azuma M, Yamamoto R, Fujimoto S, Nishi S. Biochemical characterization of alpha-fetoprotein and other serum proteins produced by a uterine endometrial adeno-carcinoma. Jpn J Cancer Res 1996;87:612–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Joseph MG, Fellows FG, Hearn SA. Primary endodermal sinus tumor of the endometrium. A clinicopathologic, immunocyto-chemical, and ultrastructural study. Cancer 1990;65:297–302.

    CAS  Google Scholar 

  10. Ohta M, Sakakibara K, Mizuno K, et al. Successful treatment of primary endodermal sinus tumor of the endometrium. Gynecol Oncol 1988;31:357–364.

    Article  CAS  PubMed  Google Scholar 

  11. Matsukuma K, Tsukamoto N. Alpha-fetoprotein producing endometrial adenocarcinoma: Report of a case. Gynecol Oncol 1988;29:370–7.

    Article  CAS  PubMed  Google Scholar 

  12. Yu H, Rohan T. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 2000;92:1472–89.

    Article  CAS  PubMed  Google Scholar 

  13. Koutsilieris M, Akoum A, Lazure C, Frenette G, Lemay A. N-terminal truncated forms of insulin-like growth factor binding protein-3 in the peritoneal fluid of women without laparoscopic evidence of endometriosis. Fertil Steril 1995;63:314–21.

    Article  CAS  PubMed  Google Scholar 

  14. Druckmann R, Rohr UD. IGF-1 in gynaecology and obstetrics: Update 2002. Maturitas 2002;41 Suppl 1:S65–S83.

    Article  CAS  PubMed  Google Scholar 

  15. Holbro T, Civenni G, Hynes NE. The ErbB receptors and their role in cancer progression. Exp Cell Res 2003;284:99–110.

    Article  CAS  PubMed  Google Scholar 

  16. Ebert AD, Wechselberger C, Martinez-Lacaci I, Bianco C, Weitzel HK, Salomon DS. Expression and function of EGF-related peptides and their receptors in gynecological cancer—from basic science to therapy. J Recept Signal Transduct Res 2000;20:1–46.

    Article  CAS  PubMed  Google Scholar 

  17. Cirisano FD, Karlan BY. The role of the HER-2/neu oncogene in gynecologic cancers. J Soc Gynecol Investig 1996;3:99–105.

    CAS  PubMed  Google Scholar 

  18. Brandt-Rauf PW. The c-erbB transmembrane growth factor receptors as serum biomarkers in human cancer studies. Mutat Res 1995;333:203–8.

    Article  CAS  PubMed  Google Scholar 

  19. Meden H, Kuhn W. Overexpression of the oncogene c-erbB-2 (HER2/neu) in ovarian cancer: A new prognostic factor. Eur J Obstet Gynecol Reprod Biol 1997;71:173–9.

    Article  CAS  PubMed  Google Scholar 

  20. Pittaway DE. Serum markers of endometrium and endometriosis. In: Diamond MP, Osteen KG, eds. Endometrium and endometriosis. Maiden: Blackwell Science, 1997:31–41.

    Google Scholar 

  21. Gagne D, Rivard M, Page M, Shazand K, Hugo P, Gosselin D. Blood leukocyte subsets are modulated in patients with endometriosis. Fertil Steril 2003;80:43–53.

    Article  PubMed  Google Scholar 

  22. American Society for Reproductive Medicine (ASRM). Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 1997;67:817–21.

    Article  Google Scholar 

  23. Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Am J Obstet Gynecol 1975;122:262–3.

    Article  CAS  PubMed  Google Scholar 

  24. Zhou J, Dsupin BA, Giudice LC, Bondy CA. Insulinlike growth factor system gene expression in human endometrium during the menstrual cycle. J Clin Endocrinol Metab 1994;79:1723–34.

    CAS  PubMed  Google Scholar 

  25. Moller B, Rasmussen C, Lindblom B, Olovsson M. Expression of the angiogenic growth factors VEGF, FGF-2, EGF and their receptors in normal human endometrium during the menstrual cycle. Mol Hum Reprod 2001;7:65–72.

    Article  CAS  PubMed  Google Scholar 

  26. Imai T, Kurachi H, Adachi K, et al. Changes in epidermal growth factor receptor and the levels of its ligands during menstrual cycle in human endometrium. Biol Reprod 1995;52:928–38.

    Article  CAS  PubMed  Google Scholar 

  27. Akinbiyi AA. Unexplained elevated maternal serum alphafeto-protein in singleton pregnancies as a predictor of fetal risk. Int J Gynaecol Obstet 1996;53:17–21.

    Article  CAS  PubMed  Google Scholar 

  28. Moore MP, Redman CW. Case-control study of severe preeclampsia of early onset. Br Med J (Clin Res Ed) 1983;287:580–3.

    Article  CAS  Google Scholar 

  29. Vollenhoven BJ, Herington AC, Healy DL. Messenger ribonucleic acid expression of the insulin-like growth factors and their binding proteins in uterine fibroids and myometrium. J Clin Endocrinol Metab 1993;76:1106–10.

    CAS  PubMed  Google Scholar 

  30. Wang DP, Konishi I, Koshiyama M, et al. Immunohistochemical localization of c-erbB-2 protein and epidermal growth factor receptor in normal surface epithelium, surface inclusion cysts, and common epithelial tumours of the ovary. Virchows Arch A Pathol Anat Histopathol 1992;421:393–400.

    Article  CAS  PubMed  Google Scholar 

  31. Inaji H, Koyama H, Motomura K, et al. Simultaneous assay of erbB-2 protein and carcinoembryonic antigen in cyst fluid as an aid in diagnosing cystic lesions of the breast. Breast Cancer 1994;1:25–30.

    Article  CAS  PubMed  Google Scholar 

  32. Harrison-Woolrych ML, Charnock-Jones DS, Smith SK. Quantification of messenger ribonucleic acid for epidermal growth factor in human myometrium and leiomyomata using reverse transcriptase polymerase chain reaction. J Clin Endocrinol Metab 1994;78:1179–84.

    CAS  PubMed  Google Scholar 

  33. Yeh J, Rein M, Nowak R. Presence of messenger ribonucleic acid for epidermal growth factor (EGF) and EGF receptor demonstrable in monolayer cell cultures of myometria and leiomyomata. Fertil Steril 1991;56:997–1000.

    Article  CAS  PubMed  Google Scholar 

  34. Kitawaki J, Koshiba H, Ishihara H, Kusuki I, Tsukamoto K, Honjo H. Progesterone induction of 17beta-hydroxysteroid de-hydrogenase type 2 during the secretory phase occurs in the endometrium of estrogen-dependent benign diseases but not in normal endometrium. J Clin Endocrinol Metab 2000;85:3292–6.

    CAS  PubMed  Google Scholar 

  35. Osteen KG, Bruner-Tran KL, Keller NR, Eisenberg E. Progesterone-mediated endometrial maturation limits matrix metallo-proteinase (MMP) expression in an inflammatory-like environment: A regulatory system altered in endometriosis. Ann N Y Acad Sci 2002;955:37–47.

    Article  CAS  PubMed  Google Scholar 

  36. Gagne D, Page M, Robitaille G, Hugo P, Gosselin D. Levels of vascular endothelial growth factor (VEGF) in serum of patients with endometriosis. Hum Reprod 2003;18:1674–80.

    Article  CAS  PubMed  Google Scholar 

  37. Steff AM, Gagne D, Page M, Rioux A, Hugo P, Gosselin D. Serum concentrations of insulin-like growth factor-1, soluble tumor necrosis factor receptor-1 and angiogenin in endometriosis patients. Am J Reprod Immunol 2004;51:166–73.

    Article  PubMed  Google Scholar 

  38. Hoppener JW, Mosselman S, Roholl PJ, et al. Expression of insulin-like growth factor-I and -II genes in human smooth muscle tumours. EMBO J 1988;7:1379–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Boehm KD, Daimon M, Gorodeski IG, Sheean LA, Utian WH, Ilan J. Expression of the insulin-like and platelet-derived growth factor genes in human uterine tissues. Mol Reprod Dev 1990;27:93–101.

    Article  CAS  PubMed  Google Scholar 

  40. Strawn EY Jr, Novy MJ, Burry KA, Bethea CL. Insulinlike growth factor I promotes leiomyoma cell growth in vitro. Am J Obstet Gynecol 1995;172:1837–43.

    Article  CAS  PubMed  Google Scholar 

  41. Abrao MS, Podgaec S, Pinotti JA, De Oliveira RM. Tumor markers in endometriosis. Int J Gynaecol Obstet 1999;66:19–22.

    Article  CAS  PubMed  Google Scholar 

  42. Akoum A, Lemay A, Lajeunesse Y, Marois M, Koutsilieris M. Immunohistochemical localization of insulin-like growth factor-binding protein-3 in eutopic and ectopic endometrial tissues. Fertil Steril 1999;72:1085–92.

    Article  CAS  PubMed  Google Scholar 

  43. Taskin O, Giudice L, Manga R, et al. Insulinlike growth factor binding proteins in peritoneal fluid of women with minimal and mild endometriosis. Hum Reprod 1996;11:1741–6.

    Article  CAS  PubMed  Google Scholar 

  44. Kim JG, Suh CS, Kim SH, Choi YM, Moon SY, Lee JY. Insulinlike growth factors (IGFs), IGF-binding proteins (IG-FBPs), and IGFBP-3 protease activity in the peritoneal fluid of patients with and without endometriosis. Fertil Steril 2000;73:996–1000.

    Article  CAS  PubMed  Google Scholar 

  45. Gurgan T, Bukulmez O, Yarali H, Tanir M, Akyildiz S. Serum and peritoneal fluid levels of IGF I and II and insulinlike growth binding protein-3 in endometriosis. J Reprod Med 1999;44:450–4.

    CAS  PubMed  Google Scholar 

  46. Bergqvist A, Borg A, Ljungberg O. Protooncogenes in endometriotic and endometrial tissue. Ann N Y Acad Sci 1991;626:276–83.

    Article  CAS  PubMed  Google Scholar 

  47. Hammond MG, Oh ST, Anners J, Surrey ES, Halme J. The effect of growth factors on the proliferation of human endometrial stromal cells in culture. Am J Obstet Gynecol 1993;168:1131–6.

    Article  CAS  PubMed  Google Scholar 

  48. Taketani Y, Mizuno M. Hormonal regulation of endometriotic cell growth in primary cell culture system. Arch Gynecol Obstet 1992;251:127–32.

    Article  CAS  PubMed  Google Scholar 

  49. Taylor RN, Lebovic DI, Mueller MD. Angiogenic factors in endometriosis. Ann N Y Acad Sci 2002;955:89–100.

    Article  CAS  PubMed  Google Scholar 

  50. Nisolle M, Casanas-Roux F, Anaf V, Mine JM, Donnez J. Morphometric study of the stromal vascularization in peritoneal endometriosis. Fertil Steril 1993;59:681–4.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Diane Gosselin PhD.

Additional information

The authors thank Julie Poliquin-Fleury, Martin Pagé, and the team of technicians for their excellent technical assistance. The authors are also grateful to all the clinicians for their invaluable collaboration in sample and data collection. Finally, this study would not have been possible without the generous contribution of all women who participated in this work.

Supported by a grant of the Industrial Research Assistance Program (IRAP) from the Natural Sciences and Engineering Research Council of Canada (NSERC) grant #15453Q, Ottawa, Ontario, Canada and by internal resources at PROCREA BioSciences, Montreal, Quebec, Canada.

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Philippoussis, F., Gagné, D., Hugo, P. et al. Concentrations of Alpha-Fetoprotein, Insulin-Like Growth Factor Binding Protein-3, c-erbB-2, and Epidermal Growth Factor in Serum of Patients With Endometriosis. Reprod. Sci. 11, 175–181 (2004). https://doi.org/10.1016/j.jsgi.2003.10.005

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