Article Data

  • Views 505
  • Dowloads 140

Original Research

Open Access

Concentrations of follicle stimulating hormone are increased in ovarian tumor fluid: implications for the management of ovarian cancer

  • A. Chudecka-Glaz1
  • I. Rzepka-Górska1,*,

1Chair and Department of Gynecological Surgery and Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland

DOI: 10.12892/ejgo20080137 Vol.29,Issue 1,January 2008 pp.37-42

Published: 10 January 2008

*Corresponding Author(s): I. Rzepka-Górska E-mail: IzGorska@sci.pam.szczecin.pl

Abstract

Purpose of investigation. Significant progress has been made in recent years in the understanding of the mechanisms postulated by the gonadotropin theory of ovarian carcinogenesis. In the present study we compare FSH concentrations between serum and fluid from cysts or the rectouterine pouch of patients with epithelial tumors and non-neoplastic lesions. Methods. We enrolled 277 patients. They were divided into five groups: I (n = 44) - ovarian cancer patients, 11 (n = 16) - borderline tumors, III (n = 40) - benign epithelial cystadenomas, IV (n = 137) - non-neoplastic lesions and V (n = 22) - admitted for "second-look" laparoscopy. Results. There were any significant differences between FSH concentrations in serum and tumor fluid in patients with ovarian cancer (36.46 vs 28.11 mIU/ml) and borderline epithelial tumors (31.5 vs 22.7 mIU/ml). For benign cystadenomas the respective concentrations were 28.96 mIU/ml in serum and 6.93 mIU/ml in tumor fluid in these groups p < 0,0000001. The same highly significant differences were found in non-neoplastic lesions (24.97 vs 4.77 mIU/ml), p < 0,0000001. Patients who underwent "second-look" laparoscopy demonstrated significant differences (p < 0.05) as FSH concentration in serum and peritoneal fluid when neoplastic cells were not disclosed, but the difference was not significant (p = 0.752) when fluid from the rectouterine pouch was positive for carcinoma cells. Conclusions. The results of our study can reflect an ineffective tumor: blood barrier and easy diffusion of gonadotropins into the tumor tissue. Local reduction of FSH levels through administration of GnRH analogs may in some clinical situations produce clear therapeutic benefits for the management of ovarian malignancies.

Keywords

Ovarian cancer; Etiopathogenesis; Gonadotropins; GnRH analogs; Treatment

Cite and Share

A. Chudecka-Glaz,I. Rzepka-Górska. Concentrations of follicle stimulating hormone are increased in ovarian tumor fluid: implications for the management of ovarian cancer. European Journal of Gynaecological Oncology. 2008. 29(1);37-42.

References

[1] Greenlee R.T., Hill-Harmon M.B., Murray T., Thun M.: “Cancer statistics”. CA Cancer. J. Clin., 2001, 51, 15.

[2] Piccart M.J., Bertelsen K., James K., Cassidy J., Mangioni C., Simonsen E. et al.: “Randomized intergroup trial of cisplatin – paclitaxel versus cisplatin-cyclophosphamide in women with advanced ovarian epithelial ovarian cancer: three-year results”. J. Natl. Cancer. Inst., 2000, 92, 699.

[3] Stewart S.L., Querec T.D., Ochman A.R. et al.: “Characterization of a carcinogenesis rat model of ovarian preneoplasia and neoplasia”. Cancer Res., 2004, 64, 8177.

[4] Choi J.H., Choi K.C., Auersperg N., Leung P.C.: “Gonadotropins activate proteolysis and increase invasion through protein kinase A and phosphatidylinositol 3-kinase pathways in human epithelial ovarian cancer cells”. Cancer Res., 2006, 66, 3912.

[5] Choi J.H., Choi K.C., Auersperg N., Leung P.C.: “Gonadotropins upregulate the epidermal growth factor receptor through activation of mitogen-activated protein kinases and phosphatidyl-inositol-3- kinase in human ovarian surface epithelial cells”. Endocr. Relat. Cancer, 2005, 12, 407.

[6] Vanderhyden B.C.: “Loss of ovarian function and the risk of ovarian cancer”. Cell Tissue Res., 2005, 322, 117.

[7] Choi J.H., Choi K.C., Auersperg N., Leung P.C.: “Differential regulation of two forms of gonadotropin-releasing hormone messenger ribonucleic acid by gonadotropins in human immortalized ovarian surface epithelium and ovarian cancer cells”. Endocr. Relat. Cancer, 2006, 13, 641.

[8] Konishi I.: “Gonadotropins and ovarian carcinogenesis: a new area of basic research and its clinical implications”. Int. J. Gynecol. Cancer, 2006, 1, 16.

[9] Ji Q., Liu P.I., Chen P.K., Aoyama C.: “Follicle stimulating hormone - induced growth promotion and gene expression profiles on ovarian surface epithelial cells”. Int. J. Cancer, 2004, 112 ,803.

[10] Pon Y.L., Auerspreg N., Wong A.S.: “Gonadotropins regulate Ncadherin-mediated human ovarian surface epithelial cell survival at both post-translational and transcriptional levels through a cyclic AMP/protein kinase A pathway”. J. Biol. Chem., 2005, 280, 15438.

[11] Parrot J.A., Doraiswamy V., Kim G., Mosher R., Skinner M.K.: “Expression and actions of both the follicle stimulating hormone receptor and luteinizing hormone receptor in normal ovarian surface epithelium and ovarian cancer”. Mol. Cell. Endocrinol., 2001, 172, 213.

[12] Syed V., Ulinski G., Mok S..C Yiu G..K, Ho S.M.: “Expression of gonadotropin receptor and growth responses to key reproductive hormones in normal and malignant human ovarian surface epithelial cells”. Cancer Res., 2001, 61, 6768.

[13] Choi K.C., Kang S.K., Tai C.J., Auersperg N., Leung P.C.:” Follicle– stimulating hormone activates mitogen – activated protein kinase in preneoplastic and neoplastic ovarian surface epithelial cells”. J. Clin. Endocrinol. Metab., 2002, 87, 2245.

[14] Choi J.H., Choi K.C., Auersperg N., Leung P.:”C. Overexpression of follicle stimulating hormone receptor activates oncogenic pathways in preneoplastic ovarian surface epithelial cells”. J. Clin. Endocrinol. Metab., 2004, 89, 5508.

[15] Schiffenbauer Y.S., Abramowitch R., Meir G.: “Loss of ovarian function promotes angiogenesis in human ovarian carcinoma”. Proc. Natl. Acad. Sci. USA, 1997, 94, 13202.

[16] Chudecka-Glaz A., Rzepka-Górska I., Kosmowska B.: “Gona - dotropin (LH, FSH) levels in serum and cyst fluid in epithelial tumors of the ovary”. Arch. Obstet. Gynecol., 2004, 270, 151.

[17] Rzepka-Górska I., Chudecka-Glaz A., Kosmowska B.: “FSH and LH serum/tumor fluid ratios and malignant tumors of the ovary”. Endocr. Releat. Cancer, 2004, 11, 315.

[18] Rzepka-Górska I.: “Ovarian cancer in child”. In: Markowska J. (ed.), Gynecological Oncology. Wroclaw: Urban & Partner, 2002, 900.

[19] Rzepka-Górska I., Tarnowski B., Chudecka-Glaz A., Górski B., Zielilska D., Toloczko-Grabarek A.:” Premature menopause in patients with BRCA 1 gene mutation”. Breast Cancer Res. Treat., 2006, 100, 59.

[20] Grundker C., Emons G.: “Role of gonadotropin-releasing hor - mone (GnRH) in ovarian cancer”. Reprod. Biol. Endocrinol., 2003, 1, 65.

[21] Qi L., Nett T.M., Allen M.C., Sha X., Harrison G.S., Frederick B.A. et al.: “Binding and cytotoxicity of conjugated and recombinant fusion proteins target to the gona do tro pin-releasing hormone receptor”. Cancer Res., 2004, 64, 2090.

[22] Zidan J., Zohar S., Mijiritzky I., Kral S., Bilenca B.: “Treating relapsed epithelial ovarian cancer with luteinizing hormone-releasing agonist (goserelin) after failure of chemotherapy”. Isr. Med. Assoc. J., 2002, 4, 597.

[23] Nagy A., Schally A.V.: “Targeting of cytotoxic luteinizing hormone-releasing hormone analogs to breast, ovarian, endometrial and prostate cancer”. Biol. Reprod., 2005, 73, 851.

[24] Biskind M.S., Biskind J.: “R. Development of tumours in the rat ovary after transplantation into the spleen”. Proc. Soc. Exp. Biol. Med., 1944, 55, 176.

[25] Mandai M., Konishi I., Kuroda H., Fukumoto M., Komatsu T., Yamamoto S., et al.:“Messenger ribonucleic acid expression of LH/hCG receptor gene in human ovarian carcinomas”. Eur. J. Cancer, 1997, 33, 1501.

[26] Kakar S.S, Grizzle W.E., Neill J.D.: “The nucleotide sequences of human GnRH receptors in breast and ovarian tumors are identical with that found in pituitary”. Mol. Cell. Endocrinol., 1994, 106, 145.

[27] Irmer G., Burger C., Muller R., Ortmann O., Peter U., Kakar S. et al.: “Expression of the messenger RNA s for Luteinizing hor mo -ne-releasing hormone (LHRH) and its receptor in human ovarian epithelial carcinoma”. Cancer Res., 1995, 55, 817.

[28] Lind M.J., Cantwell B.M., Millward M.J., Robinson A., Proctar M., Simmons D. et al.: “A phase II trial of goserelin (zoladex) in relapsed epithelial ovarian cancer”. Br. J. Cancer, 1992, 65, 621.

[29] Paskeviciute L., Roed H., Engelholm S.: “No rules without exception: long-term complete remission observed in a study using a LH-RH agonist in platinum-refractory ovarian cancer”. Gynecol. Oncol., 2002, 86, 297.

[30] Hasan J., Ton N., Mullamitha S., Clamp A., McNeilly A., Marshall E. et al.: “Phase II trial of tamoxifen and goserelin in recurrent epithelial ovarian cancer”. Br. J. Cancer, 2005, 93, 647.

[31] Rzepka-Górska I., Chudecka-Glaz A., Kolmider M., Malecha M.: “GnRH analogues as an adjuvant therapy for ovarian cancer patients”. Int. J. Gynaecol. Obstet., 2003, 81, 199.

[32] Imai A., Suygiama M., Furui T.: “Tamaya T. G1 protein-mediated translocation of serine/threonine phosphatase to the plasma membrane and apoptosis of ovarian cancer cell in response to gona-dotropin-releasing hormone antagonist cetrorelix”. J. Obstet. Gynecol., 2006, 1, 37.

[33] Kim K.Y., Choi K.C., Park S.H., Chou C.S., Auersperg N., Leung P.C.: “Type II gonadotropin-releasing hormone stimulates p38 mitogen-activated protein kinase and apoptosis in ovarian cancer cells”. J. Clin. Endocrinol., 2004, 89, 3020.

[34] Kim K.Y., Choi K.C., Auersperg N., Leung P.C.: “Mechanism of gonadotropin-releasing hormone (GnRH)-I and II-induced cell growth inhibition in ovarian cancer cells: role of the GnRH-I receptor and protein kinase C pathway”. Endocr. Relat. Cancer, 2006, 1, 211.

[35] Tang X., Yano T., Osuga Y., Matsumi H., Yano N., Xu J. et al.: “Cellular mechanisms of growth inhibition of human epithelial ovarian cancer cell line by LH- releasing hormone antagonist cetrorelix”. J. Clin. Endocrinol. Metab., 2002, 87, 3721.

[36] Grundker C., Gunthert A.R., Westphalen S., Emons G.: “Biology of the GnRH system in human gynecological cancers”. Eur. J. Endocrinol., 2002, 146, 1.

[37] Grundker C., Volker P., Gunthert A.R., Emons G.: “Antiproliferative signaling of LHRH in human endometrial and ovarian cancer mediated activation of phosphotyrosine phosphatase”. Endocrinology, 2001, 142, 2369.

[38] Imai A., Takagi A., Horibe S., Takagi H., Tamaya T.: “Evidence for tight coupling of gonadotropin-releasing hormone receptor to stimulated Fas ligand expression in reproductive tract tumors: possible mechanism for hormonal control of apoptotic cell death”. J. Clin. Endocrinol. Metab., 1998 , 83, 427.

[39] Yamauchi J., Itoh H., Shinoura H., Miyamoto Y., Hirasawa A., Kaziro Y. et al.: “Involvement of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase in A1B-adrenergic receptor/Gaqinduced inhibition cell proliferation”. Biochem. Biophys. Res. Commun., 2001, 281, 1019.

[40] Ohtani K., Sakamoto H., Kikuchi A., Nakayama Y., Idei T., Igarashi N. et al.: “Follicle-stimulating hormone promotes the growth of human epithelial ovarian cancer cells through the protein kinase cmediated system”. Cancer Lett., 2001, 166, 207.

[41] Kraemer S., Jager W.H., Lang N.: “Growth regulation effects of gonadotropin induced steroidogenic response in human ovarian cancer”. Anticancer Res., 2001, 21, 2005.

[42] Schiffenbauer Y.S., Meir G., Maoz M., Even-Ram S.C., Bar-Shavit R., Neeman M.: “Gonadotropin stimulation of MLS kuman epithelial ovarian carcinoma cells augments cell adhesion mediated by CD44 and by alpha(v)-integrin”. Gynecol. Oncol., 2002, 84, 296.

[43] Rasila K.K., Burger R.A., Smith H., Lee F.C., Verschraegen C.: “Angiogenesis in gynecological oncology-mechanism of tumor progression and therapeutic targets”. Int. J. Gynecol. Cancer, 2005, 15, 710.

[44] Carmeliet P., Jain R.K.: “Angiogenesis in cancer and other diseases”. Nature, 2000, 7, 249.

[45] Manenti L., Riccardi E., Marchini S., Naumova E., Floriani I., Garofalo A.: “Circulating plasma vascular endothelial growth factor in mice bearing human ovarian carcinoma xenograft correlates with tumor progression and response to therapy”. Mol. Cancer Ther., 2005, 4, 715.

[46] Li L., Wang L., Zhang W., Tang B., Zhang J., Song H. et al.: “Correlation of serum VEGF levels with clinical stage, therapy efficiency, tumor metastasis and patient survival in ovarian cancer”. Anticancer Res., 2004, 24, 1973.

[47] Nishida N., Yano H., Komai K., Nishida T., Kamura T., Kojiro M.:” Vascular endothelial growth factor C and vascular endothelial growth factor receptor 2 are related closely to the prognosis of patients with ovarian carcinoma”. Cancer, 2004, 101, 1364.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time

Conferences

Top