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Published in: Pathology & Oncology Research 1/2009

01-03-2009 | Original Paper

Investigation of Soluble HER2 and Transforming Growth Factor Beta-1 Serum Levels in Gestational Trophoblastic Disease

Authors: Alamtaj Samsami Dehaghani, Neda Rahimi Rad, Mohammad Javad Fattahi, Baharak Khadang, Mohammad Amin Kashef , Zahra Sarraf, Abbas Ghaderi

Published in: Pathology & Oncology Research | Issue 1/2009

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Abstract

HER2/neu and TGF-β1 are over-expressed in various types of malignancies. It appears that they play an important role in the biologic behavior of tumors and have prognostic value. Gestational tropoblastic diseases (GTDs) comprise of a heterogeneous group characterized by abnormally proliferating trophoblastic tissues, ranging from benign to malignant. The objective of this study was to measure and compare the serum levels of s-HER2 and TGF-β between patients with GTDs and pregnant and non-pregnant controls. Serum levels of s-HER2 and TGF-β1 were determined by ELISA method in 95 GTD patients (55 complete moles, 32 persistent moles, and 8 choriocarcinoma), 30 normal pregnant controls, and 22 normal non-pregnant controls. Mean serum level of s-HER2 did not differ significantly between patients and controls. TGF-β1 serum level was significantly higher in GTD patients (20.29 ± 10.68 pg/ml with 95% confidence interval (CI) of 18.10–22.48 pg/ml) compared with pregnant controls (10.26 ± 11.84 pg/ml with 95% CI of 5.75–14.76 pg/ml) and non-pregnant controls (7.27 ± 9.61 pg/ml with 95% CI of 3.01–11.53 pg/ml) (P < 0.001). Our findings suggest that TGF-β1 serum levels in GTD patients may represent a potential prognostic marker. Further investigations with larger sample size and more frequent sampling are required to elucidate this issue.
Literature
1.
go back to reference Genest DR, Berkowitz RS, Fisher RA, Newlands ES, Fehr M (2003) Gestational trophoblastic disease. In: Tavassoli FA, Devilee P (eds) World Health Organization Classification of Tumors. Pathology and Genetics. Tumors of the Breast and Female Genital Organs. IARC, Lyon, pp 250–254 Genest DR, Berkowitz RS, Fisher RA, Newlands ES, Fehr M (2003) Gestational trophoblastic disease. In: Tavassoli FA, Devilee P (eds) World Health Organization Classification of Tumors. Pathology and Genetics. Tumors of the Breast and Female Genital Organs. IARC, Lyon, pp 250–254
2.
go back to reference Sivanesaratnam V (2003) Management of gestational trophoblastic disease in developing countries. Best Pract Res Clin Obstet Gynaecol 17:925–42PubMedCrossRef Sivanesaratnam V (2003) Management of gestational trophoblastic disease in developing countries. Best Pract Res Clin Obstet Gynaecol 17:925–42PubMedCrossRef
3.
go back to reference Hung MC, Lau YK (1999) Basic science of HER2/neu: a review. Semin Oncol 26:51–59PubMed Hung MC, Lau YK (1999) Basic science of HER2/neu: a review. Semin Oncol 26:51–59PubMed
4.
go back to reference Hung MC, Schechter AL, Chevray PY, Stern DF, Weinberg RA (1986) Molecular cloning of the neu gene: absence of gross structural alteration in oncogenic alleles. Proc Natl Acad Sci U S A 83:261–264PubMedCrossRef Hung MC, Schechter AL, Chevray PY, Stern DF, Weinberg RA (1986) Molecular cloning of the neu gene: absence of gross structural alteration in oncogenic alleles. Proc Natl Acad Sci U S A 83:261–264PubMedCrossRef
5.
go back to reference Worthylake R, Opresko LK, Wiley HS (1999) ErbB-2 amplification inhibits down-regulation and induces constitutive activation of both ErbB-2 and epidermal growth factor receptors. J Biol Chem 274:8865–8874PubMedCrossRef Worthylake R, Opresko LK, Wiley HS (1999) ErbB-2 amplification inhibits down-regulation and induces constitutive activation of both ErbB-2 and epidermal growth factor receptors. J Biol Chem 274:8865–8874PubMedCrossRef
6.
go back to reference Nunes RA, Harris LN (2002) The HER2 extracellular domain as a prognostic and predictive factor in breast cancer. Clin Breast Cancer 3:125–135PubMedCrossRef Nunes RA, Harris LN (2002) The HER2 extracellular domain as a prognostic and predictive factor in breast cancer. Clin Breast Cancer 3:125–135PubMedCrossRef
7.
go back to reference Tsuda H, Hirohashi S, Shimosato Y, Tanaka Y, Hirota T, Tsugane S, Shiraishi M, Toyoshima K, Yamamoto T, Terada M (1990) Immunohistochemical study on overexpression of c-erbB-2 protein in human breast cancer: its correlation with gene amplification and long-term survival of patients. Jpn J Cancer Res 81:327–332PubMed Tsuda H, Hirohashi S, Shimosato Y, Tanaka Y, Hirota T, Tsugane S, Shiraishi M, Toyoshima K, Yamamoto T, Terada M (1990) Immunohistochemical study on overexpression of c-erbB-2 protein in human breast cancer: its correlation with gene amplification and long-term survival of patients. Jpn J Cancer Res 81:327–332PubMed
8.
go back to reference Cirisano FD, Karlan BY (1996) The role of the HER2/neu oncogene in gynecologic cancers. J Soc Gynecol Investig 3:99–105PubMedCrossRef Cirisano FD, Karlan BY (1996) The role of the HER2/neu oncogene in gynecologic cancers. J Soc Gynecol Investig 3:99–105PubMedCrossRef
9.
go back to reference Blobe GC, Schiemann WP, Lodish HF (2000) Role of transforming growth factor beta in human disease. N Engl J Med 342:1350–1358PubMedCrossRef Blobe GC, Schiemann WP, Lodish HF (2000) Role of transforming growth factor beta in human disease. N Engl J Med 342:1350–1358PubMedCrossRef
11.
go back to reference Desruisseau S, Palmari J, Giusti C, Romain S, Martin PM, Berthois Y (2006) Determination of TGFbeta1 protein level in human primary breast cancers and its relationship with survival. Br J Cancer 94:239–246PubMedCrossRef Desruisseau S, Palmari J, Giusti C, Romain S, Martin PM, Berthois Y (2006) Determination of TGFbeta1 protein level in human primary breast cancers and its relationship with survival. Br J Cancer 94:239–246PubMedCrossRef
12.
go back to reference Lin Y, Kikuchi S, Obata Y, Yagyu K, Tokyo Research Group on Prevention of Gastric Cancer (2006) Serum levels of transforming growth factor beta1 are significantly correlated with venous invasion in patients with gastric cancer. J Gastroenterol Hepatol 21:432–437PubMedCrossRef Lin Y, Kikuchi S, Obata Y, Yagyu K, Tokyo Research Group on Prevention of Gastric Cancer (2006) Serum levels of transforming growth factor beta1 are significantly correlated with venous invasion in patients with gastric cancer. J Gastroenterol Hepatol 21:432–437PubMedCrossRef
13.
go back to reference Ivanovic V, Melman A, Davis-Joseph B, Valcic M, Geliebter J (1995) Elevated plasma levels of TGF-b 1 in patients with invasive prostate cancer. Nat Med 1:282–284PubMedCrossRef Ivanovic V, Melman A, Davis-Joseph B, Valcic M, Geliebter J (1995) Elevated plasma levels of TGF-b 1 in patients with invasive prostate cancer. Nat Med 1:282–284PubMedCrossRef
14.
go back to reference Shim KS, Kim KH, Han WS, Park EB (1999) Elevated serum levels of transforming growth factor-b1 in patients with colorectal carcinoma: its association with tumor progression and its significant decrease after curative surgical resection. Cancer 85:554–561PubMedCrossRef Shim KS, Kim KH, Han WS, Park EB (1999) Elevated serum levels of transforming growth factor-b1 in patients with colorectal carcinoma: its association with tumor progression and its significant decrease after curative surgical resection. Cancer 85:554–561PubMedCrossRef
15.
go back to reference Tuncer ZS, Vegh GL, Fulop V, Genest DR, Mok SC, Berkowitz RS (2000) Expression of epidermal growth factor receptor-related family products in gestational trophoblastic diseases and normal placenta and its relationship with development of postmolar tumor. Gynecol Oncol 77:389–393PubMedCrossRef Tuncer ZS, Vegh GL, Fulop V, Genest DR, Mok SC, Berkowitz RS (2000) Expression of epidermal growth factor receptor-related family products in gestational trophoblastic diseases and normal placenta and its relationship with development of postmolar tumor. Gynecol Oncol 77:389–393PubMedCrossRef
16.
go back to reference Yang X, Zhang Z, Jia C, Li J, Yin L, Jiang S (2002) The relationship between expression of c-ras, c-erbB-2, nm23, and p53 gene products and development of trophoblastic tumor and their predictive significance for the malignant transformation of complete hydatidiform mole. Gynecol Oncol 85:438–444PubMedCrossRef Yang X, Zhang Z, Jia C, Li J, Yin L, Jiang S (2002) The relationship between expression of c-ras, c-erbB-2, nm23, and p53 gene products and development of trophoblastic tumor and their predictive significance for the malignant transformation of complete hydatidiform mole. Gynecol Oncol 85:438–444PubMedCrossRef
17.
go back to reference Pang ZJ, Xing FQ (2003) Expression of transforming growth factor-beta and insulin-like growth factor in molar and placental tissues. Arch Gynecol Obstet 269:1–4PubMedCrossRef Pang ZJ, Xing FQ (2003) Expression of transforming growth factor-beta and insulin-like growth factor in molar and placental tissues. Arch Gynecol Obstet 269:1–4PubMedCrossRef
18.
go back to reference Hegab HM, Schindler AE, Rizk M, Ramadan M (2003) Evaluation of tumour markers in molar pregnancy. Arch Gynecol Obstet 268:151–154PubMedCrossRef Hegab HM, Schindler AE, Rizk M, Ramadan M (2003) Evaluation of tumour markers in molar pregnancy. Arch Gynecol Obstet 268:151–154PubMedCrossRef
19.
20.
go back to reference Hojo M, Morimoto T, Maluccio M, Asano T, Morimoto K, Lagman M, Shimbo T, Suthanthiran M (1999) Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 397:530–534PubMedCrossRef Hojo M, Morimoto T, Maluccio M, Asano T, Morimoto K, Lagman M, Shimbo T, Suthanthiran M (1999) Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 397:530–534PubMedCrossRef
21.
22.
go back to reference Norgaard P, Hougaard S, Poulsen HS, Spang-Thomsen M (1995) Transforming growth factor b and cancer. Cancer Treat Rev 21:367–403PubMedCrossRef Norgaard P, Hougaard S, Poulsen HS, Spang-Thomsen M (1995) Transforming growth factor b and cancer. Cancer Treat Rev 21:367–403PubMedCrossRef
23.
go back to reference Saito H, Tsuj itani S, Oka S, Kondo A, Ikeguchi M, Maeta M, Kaibara N (2000) An elevated serum level of TGF-β1 significantly correlated with lymph node metastasis and poor prognosis in patients with gastric carcinoma. Anticancer Res 20:4489–4493PubMed Saito H, Tsuj itani S, Oka S, Kondo A, Ikeguchi M, Maeta M, Kaibara N (2000) An elevated serum level of TGF-β1 significantly correlated with lymph node metastasis and poor prognosis in patients with gastric carcinoma. Anticancer Res 20:4489–4493PubMed
24.
go back to reference Fukuchi M, Miyazaki T, Fukai Y, Nakajima M, Sohda M, Masuda N, Manda R, Tsukada K, Kato H, Kuwano H (2004) Plasma level of transforming growth factor beta1 measured from the azygos vein predicts prognosis in patients with esophageal cancer. Clin Cancer Res 10:2738–2741PubMedCrossRef Fukuchi M, Miyazaki T, Fukai Y, Nakajima M, Sohda M, Masuda N, Manda R, Tsukada K, Kato H, Kuwano H (2004) Plasma level of transforming growth factor beta1 measured from the azygos vein predicts prognosis in patients with esophageal cancer. Clin Cancer Res 10:2738–2741PubMedCrossRef
25.
go back to reference Glick AB, Kulkarni AB, Tennenbaum T, Hennings H, Flanders KC, O'Reilly M (1993) Loss of expression of transforming growth factor beta in skin and skin tumors is associated with hyperproliferation and a high risk for malignant conversion. Proc Natl Acad Sci U S A 90:6076–6080PubMedCrossRef Glick AB, Kulkarni AB, Tennenbaum T, Hennings H, Flanders KC, O'Reilly M (1993) Loss of expression of transforming growth factor beta in skin and skin tumors is associated with hyperproliferation and a high risk for malignant conversion. Proc Natl Acad Sci U S A 90:6076–6080PubMedCrossRef
Metadata
Title
Investigation of Soluble HER2 and Transforming Growth Factor Beta-1 Serum Levels in Gestational Trophoblastic Disease
Authors
Alamtaj Samsami Dehaghani
Neda Rahimi Rad
Mohammad Javad Fattahi
Baharak Khadang
Mohammad Amin Kashef
Zahra Sarraf
Abbas Ghaderi
Publication date
01-03-2009
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 1/2009
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-008-9115-z

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