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BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Fibrillin-1 (FBN-1) a new marker of germ cell neoplasia in situ

Authors: Z. Cierna, M. Mego, I. Jurisica, K. Machalekova, M. Chovanec, V. Miskovska, D. Svetlovska, K. Kalavska, K. Rejlekova, K. Kajo, J. Mardiak, P. Babal

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

Germ cell neoplasia in situ (GCNIS), is preinvasive stage of testicular germ cell tumours (TGCTs). Fibrillins, which are integral components of microfibrils are suggested to be involved in cancer pathogenesis and maintenance of embryonic stem cells pluripotency. The aim of this study was to examine fibrillin-1 (FBN-1) expression in TGCTs patients.

Methods

Surgical specimens from 203 patients with TGCTs were included into the translational study. FBN-1 expression was evaluated in the tumour tissue, in GCNIS and in adjacent non-neoplastic testicular tissue in all available cases. Tissue samples were processed by the tissue microarray method. FBN-1 was detected by immunohistochemistry using goat polyclonal antibody and the expression was evaluated by the multiplicative quickscore (QS).

Results

The highest FBN-1 positivity was detected in GCNIS (mean QS = 11.30), with overexpression of FBN-1 (QS >9) in the majority (77.1 %) of cases. Expression of FBN-1 in all subtypes of TGCTs was significantly lower in comparison to expression in GCNIS (all p <0.001). Seminoma had significantly higher expression compared to EC, ChC and TER (all p <0.05), but not to YST (p = 0.84). In non-neoplastic testicular tissue the FBN-1 positivity was very low (mean QS = 0.02). Sensitivity, specificity, positive and negative predictive value of FBN-1 expression for diagnosis of GCNIS were 97.1, 98.8, 98.6 and 97.7 %.

Conclusions

FBN-1 is overexpressed in TGCTs and especially in GCNIS when compared to non-neoplastic testicular tissue in patients with germ cell tumors and could be involved in germ cell neoplasia in situ development.
Literature
1.
Trabert B, Chen J, Devesa SS, Bray F, McGlynn KA. International patterns and trends in testicular cancer incidence, overall and by histologic subtype, 1973–2007. Andrology. 2015;3(1):4–12.CrossRefPubMed
2.
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. In: International Agency for Research on Cancer. Lyon; 2013.
3.
Shanmugalingam T, Soultati A, Chowdhury S, Rudman S, Van Hemelrijck M. Global incidence and outcome of testicular cancer. Clin Epidemiol. 2013;5:417–27.PubMedPubMedCentral
4.
Znaor A, Lortet-Tieulent J, Jemal A, Bray F. International variations and trends in testicular cancer incidence and mortality. Eur Urol. 2014;65(6):1095–106.CrossRef
5.
van Echten J, van Gurp RJ, Stoepker M, Looijenga LH, de Jong J, Oosterhuis W. Cytogenetic evidence that carcinoma in situ is the precursor lesion for invasive testicular germ cell tumors. Cancer Genet Cytogenet. 1995;85(2):133–7.CrossRefPubMed
6.
Hoei-Hansen CE, Rajpert-De Meyts E, Daugaard G, Skakkebaek NE. Carcinoma in situ testis, the progenitor of testicular germ cell tumours: a clinical review. Ann Oncol. 2005;16(6):863–8.CrossRefPubMed
7.
Zhang C, Berney DM, Hirsch MS, Cheng L, Ulbright TM. Evidence supporting the existence of benign teratomas of the postpubertal testis: a clinical, histopathologic, and molecular genetic analysis of 25 cases. Am J Surg Pathol. 2013;37(6):827–35.CrossRefPubMed
8.
9.
Al-Hussain T, Bakshi N, Akhtar M. Intratubular germ cell neoplasia of the testis: a brief review. Adv Anat Pathol. 2015;22(3):202–12.CrossRefPubMed
10.
Ulbright TM, Amin MB, Balzer B, Berney DM, Epstein JI, Gu C, Indrees MT, Looijenga LHJ, Paner G, Rajpert-De Meyts E, et al. Tumours of the testis and paratesticular tissue. In: Moch H, Humphrey PA, Ulbright TM, Reuter VE, editors. WHO Classification of Tumours of the Urinary System and Male Genital Organs. 4th edn. Lyon: International Agency for Research on Cancer (IARC); 2016: p. 185-258.
11.
Emerson RE, Ulbright TM. Intratubular germ cell neoplasia of the testis and its associated cancers: the use of novel biomarkers. Pathology. 2010;42(4):344–55.CrossRefPubMed
12.
Mitchell RT, E Camacho-Moll M, Macdonald J, Anderson RA, Kelnar CJ, O’Donnell M, Sharpe RM, Smith LB, Grigor KM, Wallace WH, et al. Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential. Mod Pathol. 2014;27(9):1255–66.CrossRefPubMedPubMedCentral
13.
Rajpert-De Meyts E, Bartkova J, Samson M, Hoei-Hansen CE, Frydelund-Larsen L, Bartek J, Skakkebaek NE. The emerging phenotype of the testicular carcinoma in situ germ cell. APMIS. 2003;111(1):267–78. discussion 278–269.PubMed
14.
Gueler B, Sonne SB, Zimmer J, Hilscher B, Hilscher W, Graem N, Rajpert-De Meyts E, Vogt PH. AZFa protein DDX3Y is differentially expressed in human male germ cells during development and in testicular tumours: new evidence for phenotypic plasticity of germ cells. Hum Reprod. 2012;27(6):1547–55.CrossRefPubMed
15.
Lau SK, Weiss LM, Chu PG. TCL1 protein expression in testicular germ cell tumors. Am J Clin Pathol. 2010;133(5):762–6.CrossRefPubMed
16.
Idrees M, Saxena R, Cheng L, Ulbright TM, Badve S. Podoplanin, a novel marker for seminoma: a comparison study evaluating immunohistochemical expression of podoplanin and OCT3/4. Ann Diagn Pathol. 2010;14(5):331–6.CrossRefPubMed
17.
Ye H, Ulbright TM. Difficult differential diagnoses in testicular pathology. Arch Pathol Lab Med. 2012;136(4):435–46.CrossRefPubMed
18.
Lind GE, Danielsen SA, Ahlquist T, Merok MA, Andresen K, Skotheim RI, Hektoen M, Rognum TO, Meling GI, Hoff G, et al. Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas. Mol Cancer. 2011;10:85.CrossRefPubMedPubMedCentral
19.
Guo Q, Song Y, Zhang H, Wu X, Xia P, Dang C. Detection of hypermethylated fibrillin-1 in the stool samples of colorectal cancer patients. Med Oncol. 2013;30(4):695.CrossRefPubMed
20.
Tseleni-Balafouta S, Gakiopoulou H, Fanourakis G, Voutsinas G, Litsiou H, Sozopoulos E, Balafoutas D, Patsouris E. Fibrillin expression and localization in various types of carcinomas of the thyroid gland. Mod Pathol. 2006;19(5):695–700.CrossRefPubMed
21.
Hagihara A, Miyamoto K, Furuta J, Hiraoka N, Wakazono K, Seki S, Fukushima S, Tsao MS, Sugimura T, Ushijima T. Identification of 27 5′ CpG islands aberrantly methylated and 13 genes silenced in human pancreatic cancers. Oncogene. 2004;23(53):8705–10.CrossRefPubMed
22.
Chen H, Suzuki M, Nakamura Y, Ohira M, Ando S, Iida T, Nakajima T, Nakagawara A, Kimura H. Aberrant methylation of FBN2 in human non-small cell lung cancer. Lung Cancer. 2005;50(1):43–9.CrossRefPubMed
23.
Yadin DA, Robertson IB, McNaught-Davis J, Evans P, Stoddart D, Handford PA, Jensen SA, Redfield C. Structure of the fibrillin-1 N-terminal domains suggests that heparan sulfate regulates the early stages of microfibril assembly. Structure. 2013;21(10):1743–56.CrossRefPubMedPubMedCentral
24.
Sabatier L, Miosge N, Hubmacher D, Lin G, Davis EC, Reinhardt DP. Fibrillin-3 expression in human development. Matrix Biol. 2011;30(1):43–52.CrossRefPubMed
25.
Ashworth JL, Kelly V, Rock MJ, Shuttleworth CA, Kielty CM. Regulation of fibrillin carboxy-terminal furin processing by N-glycosylation, and association of amino- and carboxy-terminal sequences. J Cell Sci. 1999;112(Pt 22):4163–71.PubMed
26.
Chaudhry SS, Cain SA, Morgan A, Dallas SL, Shuttleworth CA, Kielty CM. Fibrillin-1 regulates the bioavailability of TGFbeta1. J Cell Biol. 2007;176(3):355–67.CrossRefPubMedPubMedCentral
27.
Quondamatteo F, Reinhardt DP, Charbonneau NL, Pophal G, Sakai LY, Herken R. Fibrillin-1 and fibrillin-2 in human embryonic and early fetal development. Matrix Biol. 2002;21(8):637–46.CrossRefPubMed
28.
Whiteman P, Handford PA. Defective secretion of recombinant fragments of fibrillin-1: implications of protein misfolding for the pathogenesis of Marfan syndrome and related disorders. Hum Mol Genet. 2003;12(7):727–37.CrossRefPubMed
29.
Soteriou D, Iskender B, Byron A, Humphries JD, Borg-Bartolo S, Haddock MC, Baxter MA, Knight D, Humphries MJ, Kimber SJ. Comparative proteomic analysis of supportive and unsupportive extracellular matrix substrates for human embryonic stem cell maintenance. J Biol Chem. 2013;288(26):18716–31.CrossRefPubMedPubMedCentral
30.
Barbagallo F, Paronetto MP, Franco R, Chieffi P, Dolci S, Fry AM, Geremia R, Sette C. Increased expression and nuclear localization of the centrosomal kinase Nek2 in human testicular seminomas. J Pathol. 2009;217(3):431–41.CrossRefPubMed
31.
Mego M, Cierna Z, Svetlovska D, Macak D, Machalekova K, Miskovska V, Chovanec M, Usakova V, Obertova J, Babal P, et al. PARP expression in germ cell tumours. J Clin Pathol. 2013;66(7):607–12.CrossRefPubMed
32.
Ulisse S, Baldini E, Mottolese M, Sentinelli S, Gargiulo P, Valentina B, Sorrenti S, Di Benedetto A, De Antoni E, D’Armiento M. Increased expression of urokinase plasminogen activator and its cognate receptor in human seminomas. BMC Cancer. 2010;10:151.CrossRefPubMedPubMedCentral
33.
McLachlan RI, Rajpert-De Meyts E, Hoei-Hansen CE, de Kretser DM, Skakkebaek NE. Histological evaluation of the human testis--approaches to optimizing the clinical value of the assessment: mini review. Hum Reprod. 2007;22(1):2–16.CrossRefPubMed
34.
Sheikine Y, Genega E, Melamed J, Lee P, Reuter VE, Ye H. Molecular genetics of testicular germ cell tumors. Am J Cancer Res. 2012;2(2):153–67.PubMedPubMedCentral
35.
Guo G, Rodelsperger C, Digweed M, Robinson PN. Regulation of fibrillin-1 gene expression by Sp1. Gene. 2013;527(2):448–55.CrossRefPubMed
36.
Wang Z, Liu Y, Lu L, Yang L, Yin S, Wang Y, Qi Z, Meng J, Zang R, Yang G. Fibrillin-1, induced by Aurora-A but inhibited by BRCA2, promotes ovarian cancer metastasis. Oncotarget. 2015;6(9):6670–83.CrossRefPubMedPubMedCentral
37.
Esposito F, Libertini S, Franco R, Abagnale A, Marra L, Portella G, Chieffi P. Aurora B expression in post-puberal testicular germ cell tumours. J Cell Physiol. 2009;221(2):435–9.CrossRefPubMed
38.
Burum-Auensen E, Skotheim RI, Schjolberg AR, Roislien J, Lothe RA, Clausen OP. Spindle proteins are differentially expressed in the various histological subtypes of testicular germ cell tumors. J Carcinog. 2010;9:1.CrossRefPubMedPubMedCentral
39.
Davis MR, Andersson R, Severin J, de Hoon M, Bertin N, Baillie JK, Kawaji H, Sandelin A, Forrest AR, Summers KM, et al. Transcriptional profiling of the human fibrillin/LTBP gene family, key regulators of mesenchymal cell functions. Mol Genet Metab. 2014;112(1):73–83.CrossRefPubMedPubMedCentral
40.
Ozdamar B, Bose R, Barrios-Rodiles M, Wang HR, Zhang Y, Wrana JL. Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. Science. 2005;307(5715):1603–9.CrossRefPubMed
41.
Moustakas A, Heldin CH. Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci. 2007;98(10):1512–20.CrossRefPubMed
42.
Krstic J, Santibanez JF. Transforming growth factor-beta and matrix metalloproteinases: functional interactions in tumor stroma-infiltrating myeloid cells. Sci World J. 2014;2014:521754.CrossRef
43.
Dexeus FH, Logothetis CJ, Chong C, Sella A, Ogden S. Genetic abnormalities in men with germ cell tumors. J Urol. 1988;140(1):80–4.PubMed
Metadata
Title
Fibrillin-1 (FBN-1) a new marker of germ cell neoplasia in situ
Authors
Z. Cierna
M. Mego
I. Jurisica
K. Machalekova
M. Chovanec
V. Miskovska
D. Svetlovska
K. Kalavska
K. Rejlekova
K. Kajo
J. Mardiak
P. Babal
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2644-z

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