Skip to main content
Erschienen in: European Archives of Oto-Rhino-Laryngology 7/2015

01.07.2015 | Review Article

The clinical relevance of Ki-67 expression in laryngeal squamous cell carcinoma

verfasst von: Federico Maria Gioacchini, Matteo Alicandri-Ciufelli, Giuseppe Magliulo, Corrado Rubini, Livio Presutti, Massimo Re

Erschienen in: European Archives of Oto-Rhino-Laryngology | Ausgabe 7/2015

Einloggen, um Zugang zu erhalten

Abstract

The aim of this study was to determine the prognostic value of Ki-67 immunostaining in patients affected by laryngeal squamous cell carcinoma. A systematic review was carried out in a tertiary university referral center. An appropriate string was run on PubMed to retrieve articles dealing with Ki-67 immunohistochemical staining and laryngeal squamous cell carcinoma. A double cross-check was performed on citations and full-text articles by two investigators independently to review all manuscripts and perform a comprehensive quality assessment. Of 85 abstracts identified, 18 articles were included. These studies reported on 1,342 patients with histological confirmed diagnosis of laryngeal squamous cell carcinoma. Most studies showed a statistical association between Ki-67 immunohistochemical expression and at least one of the clinical and histopathological parameters considered by the authors. Overall the studies analyzed suggested that the tumoral proliferative index was statistically connected respectively with T stage (2/18), N stage (4/18), grading (6/18), disease-free survival (10/18) and overall survival (4/18). Our review strongly suggests that immunohistochemical staining of Ki-67 correlates with tumoral aggressiveness and worse prognosis in patients affected by laryngeal squamous cell carcinoma. Further high-quality prospective studies should be carried out to confirm our finding and determine the eventual differences between cancers of specific laryngeal subsites.
Literatur
1.
Zurück zum Zitat Ozdek A, Sarac S, Akyol MU, Sungur A, Yilmaz T (2004) c-myc and bcl-2 expression in supraglottic squamous cell carcinoma of the larynx. Otolaryngol Head Neck Surg 131(1):77–83CrossRefPubMed Ozdek A, Sarac S, Akyol MU, Sungur A, Yilmaz T (2004) c-myc and bcl-2 expression in supraglottic squamous cell carcinoma of the larynx. Otolaryngol Head Neck Surg 131(1):77–83CrossRefPubMed
2.
Zurück zum Zitat Dequanter D, Lothaire P (2008) The role of salvage surgery in organ preservation strategies in advanced head and neck cancer. B-ENT 4(2):77–80PubMed Dequanter D, Lothaire P (2008) The role of salvage surgery in organ preservation strategies in advanced head and neck cancer. B-ENT 4(2):77–80PubMed
3.
Zurück zum Zitat León X, López M, García J, Viza I, Orús C, Quer M (2007) Supracricoid laryngectomy as salvage surgery after failure of radiation therapy. Eur Arch Otorhinolaryngol 264(7):809–814CrossRefPubMed León X, López M, García J, Viza I, Orús C, Quer M (2007) Supracricoid laryngectomy as salvage surgery after failure of radiation therapy. Eur Arch Otorhinolaryngol 264(7):809–814CrossRefPubMed
4.
Zurück zum Zitat Theegarten D, Barfuss A, Gellrich NC, Philippou S (2007) Expression of proliferation markers PCNA and MIB 1 in verrucous squamous epithelial carcinoma of the oral cavity. Mund Kiefer Gesichtschir 1(3):133–136 Theegarten D, Barfuss A, Gellrich NC, Philippou S (2007) Expression of proliferation markers PCNA and MIB 1 in verrucous squamous epithelial carcinoma of the oral cavity. Mund Kiefer Gesichtschir 1(3):133–136
5.
Zurück zum Zitat Patel SG, Shah JP (2007) TNM staging of cancers of the head and neck: striving for uniformity among diversity. CA Cancer J Clin 55(4):242–258CrossRef Patel SG, Shah JP (2007) TNM staging of cancers of the head and neck: striving for uniformity among diversity. CA Cancer J Clin 55(4):242–258CrossRef
6.
Zurück zum Zitat Cordes C, Münzel AK, Rudolph P, Hoffmann M, Leuschner I, Gottschlich S (2009) Immunohistochemical staining of Ki-67 using the monoclonal antibody Ki-s11 is a prognostic indicator for laryngeal squamous cell carcinoma. Anticancer Res 29(4):1459–1465PubMed Cordes C, Münzel AK, Rudolph P, Hoffmann M, Leuschner I, Gottschlich S (2009) Immunohistochemical staining of Ki-67 using the monoclonal antibody Ki-s11 is a prognostic indicator for laryngeal squamous cell carcinoma. Anticancer Res 29(4):1459–1465PubMed
7.
Zurück zum Zitat Acikalin MF, Oner U, Tel N, Paşaoğlu O, Cakli H, Colak E (2009) Prognostic significance of Ki-67 expression for patients with laryngeal squamous cell carcinoma primarily treated by total laryngectomy. Eur Arch Otorhinolaryngol 261(7):376–380CrossRef Acikalin MF, Oner U, Tel N, Paşaoğlu O, Cakli H, Colak E (2009) Prognostic significance of Ki-67 expression for patients with laryngeal squamous cell carcinoma primarily treated by total laryngectomy. Eur Arch Otorhinolaryngol 261(7):376–380CrossRef
8.
Zurück zum Zitat Mielcarek-Kuchta D, Olofsson J, Golusinski W (2009) p53, Ki67 and cyclin D1 as prognosticators of lymph node metastases in laryngeal carcinoma. Eur Arch Otorhinolaryngol 260(10):549–554CrossRef Mielcarek-Kuchta D, Olofsson J, Golusinski W (2009) p53, Ki67 and cyclin D1 as prognosticators of lymph node metastases in laryngeal carcinoma. Eur Arch Otorhinolaryngol 260(10):549–554CrossRef
9.
Zurück zum Zitat Pastuszewski W, Dziegiel P, Krecicki T et al (2009) Prognostic significance of metallothionein, p53 protein and Ki-67 antigen expression in laryngeal cancer. Anticancer Res 27(1A):335–342 Pastuszewski W, Dziegiel P, Krecicki T et al (2009) Prognostic significance of metallothionein, p53 protein and Ki-67 antigen expression in laryngeal cancer. Anticancer Res 27(1A):335–342
10.
Zurück zum Zitat Kreipe H, Heidebrecht HJ, Hansen S et al (2009) A new proliferation-associated nuclear antigen detectable in paraffin-embedded tissues by the monoclonal antibody Ki-S1. Am J Pathol 142(1):3–9 Kreipe H, Heidebrecht HJ, Hansen S et al (2009) A new proliferation-associated nuclear antigen detectable in paraffin-embedded tissues by the monoclonal antibody Ki-S1. Am J Pathol 142(1):3–9
11.
Zurück zum Zitat Pich A, Chiusa L, Navone R (2004) Prognostic relevance of cell proliferation in head and neck tumors. Ann Oncol 15(9):1319–1329CrossRefPubMed Pich A, Chiusa L, Navone R (2004) Prognostic relevance of cell proliferation in head and neck tumors. Ann Oncol 15(9):1319–1329CrossRefPubMed
12.
Zurück zum Zitat Leong AS, Sormunen RT, Vinyuvat S, Hamdani RW, Suthipintawong C (2001) Biologic markers in ductal carcinoma in situ and concurrent infiltrating carcinoma. A comparison of eight contemporary grading systems. Am J Clin Pathol 115(5):709–718CrossRefPubMed Leong AS, Sormunen RT, Vinyuvat S, Hamdani RW, Suthipintawong C (2001) Biologic markers in ductal carcinoma in situ and concurrent infiltrating carcinoma. A comparison of eight contemporary grading systems. Am J Clin Pathol 115(5):709–718CrossRefPubMed
13.
Zurück zum Zitat DeRienzo DP, Greenberg SD, Fraire AE (1991) Carcinoma of the larynx. Changing incidence in women. Arch Otolaryngol Head Neck Surg 117(6):681–684CrossRefPubMed DeRienzo DP, Greenberg SD, Fraire AE (1991) Carcinoma of the larynx. Changing incidence in women. Arch Otolaryngol Head Neck Surg 117(6):681–684CrossRefPubMed
14.
Zurück zum Zitat Ambrosch P (2007) The role of laser microsurgery in the treatment of laryngeal cancer. Curr Opin Otolaryngol Head Neck Surg 15(2):82–88CrossRefPubMed Ambrosch P (2007) The role of laser microsurgery in the treatment of laryngeal cancer. Curr Opin Otolaryngol Head Neck Surg 15(2):82–88CrossRefPubMed
15.
Zurück zum Zitat Jones AS, Roland NJ, Caslin AW, Cooke TG, Cooke LD, Forster G (1994) A comparison of cellular proliferation markers in squamous cell carcinoma of the head and neck. J Laryngol Otol 108(10):859–864CrossRefPubMed Jones AS, Roland NJ, Caslin AW, Cooke TG, Cooke LD, Forster G (1994) A comparison of cellular proliferation markers in squamous cell carcinoma of the head and neck. J Laryngol Otol 108(10):859–864CrossRefPubMed
16.
Zurück zum Zitat Roland NJ, Caslin AW, Bowie GL, Jones AS (1994) Has the cellular proliferation marker Ki67 any clinical relevance in squamous cell carcinoma of the head and neck? Clin Otolaryngol Allied Sci 19(1):13–18CrossRefPubMed Roland NJ, Caslin AW, Bowie GL, Jones AS (1994) Has the cellular proliferation marker Ki67 any clinical relevance in squamous cell carcinoma of the head and neck? Clin Otolaryngol Allied Sci 19(1):13–18CrossRefPubMed
17.
Zurück zum Zitat Kearsley JH, Furlong KL, Cooke RA, Waters MJ (1990) An immunohistochemical assessment of cellular proliferation markers in head and neck squamous cell cancers. Br J Cancer 61(6):821–827CrossRefPubMedCentralPubMed Kearsley JH, Furlong KL, Cooke RA, Waters MJ (1990) An immunohistochemical assessment of cellular proliferation markers in head and neck squamous cell cancers. Br J Cancer 61(6):821–827CrossRefPubMedCentralPubMed
18.
Zurück zum Zitat Janot F, Klijanienko J, Russo A et al (1996) Prognostic value of clinicopathological parameters in head and neck squamous cell carcinoma: a prospective analysis. Br J Cancer 73(4):531–538CrossRefPubMedCentralPubMed Janot F, Klijanienko J, Russo A et al (1996) Prognostic value of clinicopathological parameters in head and neck squamous cell carcinoma: a prospective analysis. Br J Cancer 73(4):531–538CrossRefPubMedCentralPubMed
19.
Zurück zum Zitat Lazaris ACh, Rigopoulou A, Tseleni-Balafouta S et al (2002) Immunodetection and clinico-pathological correlates of two tumour growth regulators in laryngeal carcinoma. Histol Histopathol 17(1):131–138PubMed Lazaris ACh, Rigopoulou A, Tseleni-Balafouta S et al (2002) Immunodetection and clinico-pathological correlates of two tumour growth regulators in laryngeal carcinoma. Histol Histopathol 17(1):131–138PubMed
20.
Zurück zum Zitat Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by mononuclear antibody Ki-67. J Immunol 133:1710–1715PubMed Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by mononuclear antibody Ki-67. J Immunol 133:1710–1715PubMed
21.
Zurück zum Zitat Wintzer HO, Zipfel I, Schulte-Mönting J, Hellerich U, von Kleist S (1991) Ki-67 immunostaining in human breast tumors and its relationship to prognosis. Cancer 67(2):421–428CrossRefPubMed Wintzer HO, Zipfel I, Schulte-Mönting J, Hellerich U, von Kleist S (1991) Ki-67 immunostaining in human breast tumors and its relationship to prognosis. Cancer 67(2):421–428CrossRefPubMed
22.
Zurück zum Zitat Tungekar MF, Gatter KC, Dunnill MS, Mason DY (1991) Ki-67 immunostaining and survival in operable lung cancer. Histopathology 19(6):545–550CrossRefPubMed Tungekar MF, Gatter KC, Dunnill MS, Mason DY (1991) Ki-67 immunostaining and survival in operable lung cancer. Histopathology 19(6):545–550CrossRefPubMed
23.
Zurück zum Zitat Youssef EM, Matsuda T, Takada N et al (1995) Prognostic significance of the MIB-1 proliferation index for patients with squamous cell carcinoma of the esophagus. Cancer 76(3):358–366CrossRefPubMed Youssef EM, Matsuda T, Takada N et al (1995) Prognostic significance of the MIB-1 proliferation index for patients with squamous cell carcinoma of the esophagus. Cancer 76(3):358–366CrossRefPubMed
24.
Zurück zum Zitat Aaltomaa S, Lipponen P, Ala-Opas M, Eskelinen M, Syrjänen K (1997) Prognostic value of Ki-67 expression in renal cell carcinomas. Eur Urol 31(3):350–355PubMed Aaltomaa S, Lipponen P, Ala-Opas M, Eskelinen M, Syrjänen K (1997) Prognostic value of Ki-67 expression in renal cell carcinomas. Eur Urol 31(3):350–355PubMed
25.
Zurück zum Zitat Holte H, de Lange Davies C, Beiske K et al (1989) Ki67 and 4F2 antigen expression as well as DNA synthesis predict survival at relapse/tumour progression in low-grade B-cell lymphoma. Int J Cancer 44(6):975–980CrossRefPubMed Holte H, de Lange Davies C, Beiske K et al (1989) Ki67 and 4F2 antigen expression as well as DNA synthesis predict survival at relapse/tumour progression in low-grade B-cell lymphoma. Int J Cancer 44(6):975–980CrossRefPubMed
26.
Zurück zum Zitat Izawa H, Yonemitsu N, Shin T, Sugihara H (1999) Histopathological analysis of apoptosis, and expression of p53, bcl-2, bax, and Ki-67 in laryngeal squamous cell carcinomas and dysplasia. Auris Nasus Larynx 26(3):317–330CrossRefPubMed Izawa H, Yonemitsu N, Shin T, Sugihara H (1999) Histopathological analysis of apoptosis, and expression of p53, bcl-2, bax, and Ki-67 in laryngeal squamous cell carcinomas and dysplasia. Auris Nasus Larynx 26(3):317–330CrossRefPubMed
27.
Zurück zum Zitat Krecicki T, Jeleń M, Zalesska-Krecicka M, Rak J, Szkudlarek T, Jeleń-Krzeszewska J (1999) Epidermal growth factor receptor (EGFR), proliferating cell nuclear antigen (PCNA) and Ki-67 antigen in laryngeal epithelial lesions. Oral Oncol 35(2):180–186CrossRefPubMed Krecicki T, Jeleń M, Zalesska-Krecicka M, Rak J, Szkudlarek T, Jeleń-Krzeszewska J (1999) Epidermal growth factor receptor (EGFR), proliferating cell nuclear antigen (PCNA) and Ki-67 antigen in laryngeal epithelial lesions. Oral Oncol 35(2):180–186CrossRefPubMed
28.
Zurück zum Zitat Sittel C, Eckel HE, Damm M, von Pritzbuer E, Kvasnicka HM (2000) Ki-67 (MIB1), p53, and Lewis-X (LeuM1) as prognostic factors of recurrence in T1 and T2 laryngeal carcinoma. Laryngoscope 110(6):1012–1017CrossRefPubMed Sittel C, Eckel HE, Damm M, von Pritzbuer E, Kvasnicka HM (2000) Ki-67 (MIB1), p53, and Lewis-X (LeuM1) as prognostic factors of recurrence in T1 and T2 laryngeal carcinoma. Laryngoscope 110(6):1012–1017CrossRefPubMed
29.
Zurück zum Zitat Fumic-Dunkic L, Katic V, Janjanin S, Klapan I, Simuncic A, Vcev A (2003) Retrospective analysis of Ki-67 antigen expression in paraffin tissue blocks of laryngeal squamous cell carcinoma. Am J Otolaryngol 24(2):106–110CrossRefPubMed Fumic-Dunkic L, Katic V, Janjanin S, Klapan I, Simuncic A, Vcev A (2003) Retrospective analysis of Ki-67 antigen expression in paraffin tissue blocks of laryngeal squamous cell carcinoma. Am J Otolaryngol 24(2):106–110CrossRefPubMed
30.
Zurück zum Zitat Sarafoleanu D, Postelnicu V, Iosif C, Manea C, Sarafoleanu C (2009) The role of p53, PCNA and Ki-67 as outcome predictors in the treatment of laryngeal cancer. J Med Life 2(2):219–226PubMedCentralPubMed Sarafoleanu D, Postelnicu V, Iosif C, Manea C, Sarafoleanu C (2009) The role of p53, PCNA and Ki-67 as outcome predictors in the treatment of laryngeal cancer. J Med Life 2(2):219–226PubMedCentralPubMed
31.
Zurück zum Zitat Re M, Zizzi A, Ferrante L et al (2014) p63 and Ki-67 immunostainings in laryngeal squamous cell carcinoma are related to survival. Eur Arch Otorhinolaryngol 271(6):1641–1651 Re M, Zizzi A, Ferrante L et al (2014) p63 and Ki-67 immunostainings in laryngeal squamous cell carcinoma are related to survival. Eur Arch Otorhinolaryngol 271(6):1641–1651
32.
Zurück zum Zitat Liu M, Lawson G, Delos M et al (2003) Predictive value of the fraction of cancer cells immunolabeled for proliferating cell nuclear antigen or Ki67 in biopsies of head and neck carcinomas to identify lymph node metastasis: comparison with clinical and radiologic examinations. Head Neck 25(4):280–288CrossRefPubMed Liu M, Lawson G, Delos M et al (2003) Predictive value of the fraction of cancer cells immunolabeled for proliferating cell nuclear antigen or Ki67 in biopsies of head and neck carcinomas to identify lymph node metastasis: comparison with clinical and radiologic examinations. Head Neck 25(4):280–288CrossRefPubMed
33.
Zurück zum Zitat Mirza S, Jeannon JP, Soames J, Wilson JA (2006) Is Ki67 a marker for the transformation of laryngeal dysplasia to carcinoma? Acta Otolaryngol 126(4):418–421CrossRefPubMed Mirza S, Jeannon JP, Soames J, Wilson JA (2006) Is Ki67 a marker for the transformation of laryngeal dysplasia to carcinoma? Acta Otolaryngol 126(4):418–421CrossRefPubMed
34.
Zurück zum Zitat Rodrigues RB, Motta Rda R, Machado SM et al (2008) Prognostic value of the immunohistochemistry correlation of Ki-67 and p53 in squamous cell carcinomas of the larynx. Braz J Otorhinolaryngol 74(6):855–859PubMed Rodrigues RB, Motta Rda R, Machado SM et al (2008) Prognostic value of the immunohistochemistry correlation of Ki-67 and p53 in squamous cell carcinomas of the larynx. Braz J Otorhinolaryngol 74(6):855–859PubMed
35.
Zurück zum Zitat Teppo H, Soini Y, Melkko J, Koivunen P, Alho OP (2003) Prognostic factors in laryngeal carcinoma: the role of apoptosis, p53, proliferation (Ki-67) and angiogenesis. APMIS 111(4):451–457CrossRefPubMed Teppo H, Soini Y, Melkko J, Koivunen P, Alho OP (2003) Prognostic factors in laryngeal carcinoma: the role of apoptosis, p53, proliferation (Ki-67) and angiogenesis. APMIS 111(4):451–457CrossRefPubMed
36.
Zurück zum Zitat Kumar RV, Shenoy AM, Daniel R, Shah KV (2004) Cyclin D1, p53, MIB1, intratumoral microvessel density, and human papillomavirus in advanced laryngeal carcinoma: association with nodal metastasis. Otolaryngol Head Neck Surg 131(4):509–513CrossRefPubMed Kumar RV, Shenoy AM, Daniel R, Shah KV (2004) Cyclin D1, p53, MIB1, intratumoral microvessel density, and human papillomavirus in advanced laryngeal carcinoma: association with nodal metastasis. Otolaryngol Head Neck Surg 131(4):509–513CrossRefPubMed
37.
Zurück zum Zitat Kropveld A, Slootweg PJ, Blankenstein MA, Terhaard CH, Hordijk GJ (1998) Ki-67 and p53 in T2 laryngeal cancer. Laryngoscope 108(10):1548–1552CrossRefPubMed Kropveld A, Slootweg PJ, Blankenstein MA, Terhaard CH, Hordijk GJ (1998) Ki-67 and p53 in T2 laryngeal cancer. Laryngoscope 108(10):1548–1552CrossRefPubMed
38.
Zurück zum Zitat Ahmed WA, Suzuki K, Imaeda Y, Horibe Y (2008) Ki-67, p53 and epidermal growth factor receptor expression in early glottic cancer involving the anterior commissure treated with radiotherapy. Auris Nasus Larynx 35(2):213–219CrossRefPubMed Ahmed WA, Suzuki K, Imaeda Y, Horibe Y (2008) Ki-67, p53 and epidermal growth factor receptor expression in early glottic cancer involving the anterior commissure treated with radiotherapy. Auris Nasus Larynx 35(2):213–219CrossRefPubMed
39.
Zurück zum Zitat Lothaire P, de Azambuja E, Dequanter D et al (2006) Molecular markers of head and neck squamous cell carcinoma: promising signs in need of prospective evaluation. Head Neck 28(3):256–269CrossRefPubMed Lothaire P, de Azambuja E, Dequanter D et al (2006) Molecular markers of head and neck squamous cell carcinoma: promising signs in need of prospective evaluation. Head Neck 28(3):256–269CrossRefPubMed
40.
Zurück zum Zitat Sakata K, Oouchi A, Nagakura H et al (2000) Accelerated radiotherapy for T1, 2 glottic carcinoma: analysis of results with KI-67 index. Int J Radiat Oncol Biol Phys 47(1):81–88CrossRefPubMed Sakata K, Oouchi A, Nagakura H et al (2000) Accelerated radiotherapy for T1, 2 glottic carcinoma: analysis of results with KI-67 index. Int J Radiat Oncol Biol Phys 47(1):81–88CrossRefPubMed
41.
Zurück zum Zitat Saarilahti K, Kajanti M, Kouri M, Aaltonen LM, Franssila K, Joensuu H (2003) Cyclin A and Ki-67 expression as predictors for locoregional recurrence and outcome in laryngeal cancer patients treated with surgery and postoperative radiotherapy. Int J Radiat Oncol Biol Phys 57(4):986–995CrossRefPubMed Saarilahti K, Kajanti M, Kouri M, Aaltonen LM, Franssila K, Joensuu H (2003) Cyclin A and Ki-67 expression as predictors for locoregional recurrence and outcome in laryngeal cancer patients treated with surgery and postoperative radiotherapy. Int J Radiat Oncol Biol Phys 57(4):986–995CrossRefPubMed
42.
Zurück zum Zitat Nichols AC, Whelan F, Basmaji J et al (2012) Ki-67 expression predicts radiotherapy failure in early glottic cancer. J Otolaryngol Head Neck Surg 41(2):124–130PubMed Nichols AC, Whelan F, Basmaji J et al (2012) Ki-67 expression predicts radiotherapy failure in early glottic cancer. J Otolaryngol Head Neck Surg 41(2):124–130PubMed
43.
Zurück zum Zitat Lavertu P, Adelstein DJ, Myles J, Secic M (2001) P53 and Ki-67 as outcome predictors for advanced squamous cell cancers of the head and neck treated with chemoradiotherapy. Laryngoscope 111(11 Pt 1):1878–1892CrossRefPubMed Lavertu P, Adelstein DJ, Myles J, Secic M (2001) P53 and Ki-67 as outcome predictors for advanced squamous cell cancers of the head and neck treated with chemoradiotherapy. Laryngoscope 111(11 Pt 1):1878–1892CrossRefPubMed
Metadaten
Titel
The clinical relevance of Ki-67 expression in laryngeal squamous cell carcinoma
verfasst von
Federico Maria Gioacchini
Matteo Alicandri-Ciufelli
Giuseppe Magliulo
Corrado Rubini
Livio Presutti
Massimo Re
Publikationsdatum
01.07.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
European Archives of Oto-Rhino-Laryngology / Ausgabe 7/2015
Print ISSN: 0937-4477
Elektronische ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-014-3117-0

Weitere Artikel der Ausgabe 7/2015

European Archives of Oto-Rhino-Laryngology 7/2015 Zur Ausgabe

Update HNO

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.