N-cadherin expression in malignant germ cell tumours of the testis

BMC Clinical Pathology

Carl Ludwig Behnes¹  Heinz-Joachim Radzun¹  Paul Thelen³  Peter Burfeind²  Arne Strauss³  Bernhard Hemmerlein¹  Felix Bremmer¹ 

[1]Department of Pathology, University Medical Centre Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany

[2]Department of Human Genetics, University Medical Centre Göttingen, Göttingen, Germany

[3]Department of Urology, University Medical Centre Göttingen, Göttingen, Germany

关键词: TGCT cell lines;    Immunohistochemistry;    Embryonal carcinoma;    Seminoma;    N-cadherin;   

Others  :  1085278
DOI  :  10.1186/1472-6890-12-19

 received in 2012-05-16, accepted in 2012-10-03,  发布年份 2012

【 摘 要 】

Background

Testicular germ cell tumours (TGCTs) are the most common malignancy in young men aged 18–35 years. They are clinically and histologically subdivided into seminomas and non-seminomas. Cadherins are calcium-dependent transmembrane proteins of the group of adhesion proteins. They play a role in the stabilization of cell-cell contacts, the embryonic morphogenesis, in the maintenance of cell polarity and signal transduction. N-cadherin (CDH2), the neuronal cadherin, stimulates cell-cell contacts during migration and invasion of cells and is able to suppress tumour cell growth.

Methods

Tumour tissues were acquired from 113 male patients and investigated by immunohistochemistry, as were the three TGCT cell lines NCCIT, NTERA-2 and Tcam2. A monoclonal antibody against N-cadherin was used.

Results

Tumour-free testis and intratubular germ cell neoplasias (unclassified) (IGCNU) strongly expressed N-cadherin within the cytoplasm. In all seminomas investigated, N-cadherin expression displayed a membrane-bound location. In addition, the teratomas and yolk sac tumours investigated also differentially expressed N-cadherin. In contrast, no N-cadherin could be detected in any of the embryonal carcinomas and chorionic carcinomas examined. This expression pattern was also seen in the investigated mixed tumours consisting of seminomas, teratomas, and embryonal carcinoma.

Conclusions

N-cadherin expression can be used to differentiate embryonal carcinomas and chorionic carcinomas from other histological subtypes of TGCT.

【 授权许可】

   
2012 Bremmer et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Rosen A, Jayram G, Drazer M, Eggener SE: Global trends in testicular cancer incidence and mortality. Eur Urol 2011, 60(2):374-379. Epub 2011/05/27
• [2]Horwich A, Shipley J, Huddart R: Testicular germ-cell cancer. Lancet 2006, 367(9512):754-765. Epub 2006/03/07
• [3]Hoei-Hansen CE, Nielsen JE, Almstrup K, Sonne SB, Graem N, Skakkebaek NE, et al.: Transcription factor AP-2gamma is a developmentally regulated marker of testicular carcinoma in situ and germ cell tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 2004, 10(24):8521-8530. Epub 2004/12/30
• [4]Angst BD, Marcozzi C, Magee AI: The cadherin superfamily: diversity in form and function. J Cell Sci 2001, 114(Pt 4):629-641. Epub 2001/02/15
• [5]Potter E, Bergwitz C, Brabant G: The cadherin-catenin system: implications for growth and differentiation of endocrine tissues. Endocr Rev 1999, 20(2):207-239. Epub 1999/04/16
• [6]Stemmler MP: Cadherins in development and cancer. Mol Biosyst 2008, 4(8):835-850. Epub 2008/07/18
• [7]Gumbiner BM: Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol 2005, 6(8):622-634. Epub 2005/07/19
• [8]El Sayegh TY, Kapus A, McCulloch CA: Beyond the epithelium: cadherin function in fibrous connective tissues. FEBS Lett 2007, 581(2):167-174. Epub 2007/01/16
• [9]Takeichi M: The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development 1988, 102(4):639-655. Epub 1988/04/01
• [10]Balsamo J, Arregui C, Leung T, Lilien J: The nonreceptor protein tyrosine phosphatase PTP1B binds to the cytoplasmic domain of N-cadherin and regulates the cadherin-actin linkage. J Cell Biol 1998, 143(2):523-532. Epub 1998/10/24
• [11]Puch S, Armeanu S, Kibler C, Johnson KR, Muller CA, Wheelock MJ, et al.: N-cadherin is developmentally regulated and functionally involved in early hematopoietic cell differentiation. J Cell Sci 2001, 114(Pt 8):1567-1577. Epub 2001/04/03
• [12]Abutaily AS, Addis BJ, Roche WR: Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies. J Clin Pathol 2002, 55(9):662-668. Epub 2002/08/27
• [13]Thirkettle I, Harvey P, Hasleton PS, Ball RY, Warn RM: Immunoreactivity for cadherins, HGF/SF, met, and erbB-2 in pleural malignant mesotheliomas. Histopathology 2000, 36(6):522-528. Epub 2000/06/10
• [14]Han AC, Peralta-Soler A, Knudsen KA, Wheelock MJ, Johnson KR, Salazar H: Differential expression of N-cadherin in pleural mesotheliomas and E-cadherin in lung adenocarcinomas in formalin-fixed, paraffin-embedded tissues. Hum Pathol 1997, 28(6):641-645. Epub 1997/06/01
• [15]Laskin WB, Miettinen M: Epithelial-type and neural-type cadherin expression in malignant noncarcinomatous neoplasms with epithelioid features that involve the soft tissues. Arch Pathol Lab Med 2002, 126(4):425-431. Epub 2002/03/20
• [16]Peralta Soler A, Knudsen KA, Tecson-Miguel A, McBrearty FX, Han AC, Salazar H: Expression of E-cadherin and N-cadherin in surface epithelial-stromal tumors of the ovary distinguishes mucinous from serous and endometrioid tumors. Hum Pathol 1997, 28(6):734-739. Epub 1997/06/01
• [17]Markovic-Lipkovski J, Brasanac D, Muller GA, Muller CA: Cadherins and integrins in renal cell carcinoma: an immunohistochemical study. Tumori 2001, 87(3):173-178. Epub 2001/08/16
• [18]Eble JN: International Agency for Research on Cancer. Pathology and genetics of tumours of the urinary system and male genital organs. Lyon: IARC-Press 2004, 359:S p. S p
• [19]Hatta K, Takagi S, Fujisawa H, Takeichi M: Spatial and temporal expression pattern of N-cadherin cell adhesion molecules correlated with morphogenetic processes of chicken embryos. Dev Biol 1987, 120(1):215-227. Epub 1987/03/01
• [20]Hazan RB, Phillips GR, Qiao RF, Norton L, Aaronson SA: Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis. J Cell Biol 2000, 148(4):779-790. Epub 2000/02/23
• [21]Kalluri R: EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest 2009, 119(6):1417-1419. Epub 2009/06/03
• [22]Harada KI, Miyake H, Kusuda Y, Fujisawa M: Expression of epithelial-mesenchymal transition markers in renal cell carcinoma: impact on prognostic outcomes in patients undergoing radical nephrectomy. BJU Int 2012,  . Epub 2012/06/21
• [23]Nieman MT, Prudoff RS, Johnson KR, Wheelock MJ: N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression. J Cell Biol 1999, 147(3):631-644. Epub 1999/11/05
• [24]Polyak K, Weinberg RA: Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 2009, 9(4):265-273. Epub 2009/03/06
• [25]Thomson S, Buck E, Petti F, Griffin G, Brown E, Ramnarine N, et al.: Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res 2005, 65(20):9455-9462. Epub 2005/10/19
• [26]Han AC, Soler AP, Knudsen KA, Salazar H: Distinct cadherin profiles in special variant carcinomas and other tumors of the breast. Hum Pathol 1999, 30(9):1035-1039. Epub 1999/09/24
• [27]Wheelock MJ, Shintani Y, Maeda M, Fukumoto Y, Johnson KR: Cadherin switching. J Cell Sci 2008, 121(Pt 6):727-735. Epub 2008/03/07
• [28]Honecker F, Kersemaekers AM, Molier M, Van Weeren PC, Stoop H, De Krijger RR, et al.: Involvement of E-cadherin and beta-catenin in germ cell tumours and in normal male fetal germ cell development. J Pathol 2004, 204(2):167-174. Epub 2004/09/21
• [29]Saito T, Katagiri A, Watanabe R, Tanikawa T, Kawasaki T, Tomita Y, et al.: Expression of E-cadherin and catenins on testis tumor. Urol Int 2000, 65(3):140-143. Epub 2000/10/29
• [30]Hart AH, Hartley L, Parker K, Ibrahim M, Looijenga LH, Pauchnik M, et al.: The pluripotency homeobox gene NANOG is expressed in human germ cell tumors. Cancer 2005, 104(10):2092-2098. Epub 2005/10/06
• [31]Niehans GA, Manivel JC, Copland GT, Scheithauer BW, Wick MR: Immunohistochemistry of germ cell and trophoblastic neoplasms. Cancer 1988, 62(6):1113-1123. Epub 1988/09/15
• [32]Bentley AJ, Parkinson MC, Harding BN, Bains RM, Lantos PL: A comparative morphological and immunohistochemical study of testicular seminomas and intracranial germinomas. Histopathology 1990, 17(5):443-449. Epub 1990/11/01
• [33]Leroy X, Augusto D, Leteurtre E, Gosselin B: CD30 and CD117 (c-kit) used in combination are useful for distinguishing embryonal carcinoma from seminoma. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 2002, 50(2):283-285. Epub 2002/01/19
• [34]Jones TD, Ulbright TM, Eble JN, Baldridge LA, Cheng L: OCT4 staining in testicular tumors: a sensitive and specific marker for seminoma and embryonal carcinoma. Am J Surg Pathol 2004, 28(7):935-940. Epub 2004/06/30
• [35]Eglen DE, Ulbright TM: The differential diagnosis of yolk sac tumor and seminoma. Usefulness of cytokeratin, alpha-fetoprotein, and alpha-1-antitrypsin immunoperoxidase reactions. Am J Clin Pathol 1987, 88(3):328-332. Epub 1987/09/01
• [36]Suster S, Moran CA, Dominguez-Malagon H, Quevedo-Blanco P: Germ cell tumors of the mediastinum and testis: a comparative immunohistochemical study of 120 cases. Hum Pathol 1998, 29(7):737-742. Epub 1998/07/22