Skip to main content
Erschienen in: Gastric Cancer 1/2013

01.01.2013 | Original Article

HER2 expression and its clinicopathological features in resectable gastric cancer

verfasst von: Yoshiki Kataoka, Hiroshi Okabe, Akihiko Yoshizawa, Sachiko Minamiguchi, Kenichi Yoshimura, Hironori Haga, Yoshiharu Sakai

Erschienen in: Gastric Cancer | Ausgabe 1/2013

Einloggen, um Zugang zu erhalten

Abstract

Background

A recent randomized controlled trial (Trastuzumab for Gastric Cancer [ToGA] study) established standard scoring criteria of human epidermal growth factor receptor 2 (HER2) for gastric cancer and demonstrated the efficacy of trastuzumab for treating metastatic gastric cancer. The aim of the present study was to evaluate the frequency of HER2-positive cases by application of the standard criteria in patients with resectable gastric cancer and to examine the relationships between HER2 expression and prognosis, mucin phenotype, p53 status, and clinicopathological features.

Methods

A total of 213 patients were included in this retrospective study. All tumor samples were examined for HER2 expression by immunohistochemistry (IHC), HER2 amplification by in situ hybridization, and mucin and p53 expression by staining for CD10, MUC2, MUC5AC, MUC6, and p53.

Results

HER2-positive tumors were identified in 25 patients (11.7 %). HER2-positive cases were more frequently found in men, older patients, and in the intestinal histological type (P = 0.0048, 0.0309, and <0.0001, respectively). Although no association was found between HER2 overexpression and mucin phenotype, the expression of CD10 and p53 was significantly correlated with HER2 positivity (P = 0.0079 and 0.013). The overall survival of HER2-negative and -positive patients was not significantly different. However, in patients with stage III/IV, overall survival was worse in HER2-positive patients (P = 0.0149). In a comparison between dual-color in situ hybridization (DISH) and fluorescence in situ hybridization (FISH), four IHC2+/3+ cases that were DISH-positive were judged as negative by FISH.

Conclusions

Our study indicated that HER2 expression was less frequent in resectable gastric cancer than in metastatic gastric cancer. The impact of HER2 expression on survival was limited. DISH was superior to FISH for evaluating cases with limited HER2 expression.
Literatur
1.
Zurück zum Zitat Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.PubMedCrossRef Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.PubMedCrossRef
2.
Zurück zum Zitat Jørgensen JT. Targeted HER2 treatment in advanced gastric cancer. Oncology. 2010;78:26–33.PubMedCrossRef Jørgensen JT. Targeted HER2 treatment in advanced gastric cancer. Oncology. 2010;78:26–33.PubMedCrossRef
3.
Zurück zum Zitat Hofmann M, Stoss O, Shi D, Büttner R, van de Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52:797–805.PubMedCrossRef Hofmann M, Stoss O, Shi D, Büttner R, van de Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52:797–805.PubMedCrossRef
4.
Zurück zum Zitat Park DI, Yun JW, Park JH, Oh SJ, Kim HJ, Cho YK, et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci. 2006;51:1371–9.PubMedCrossRef Park DI, Yun JW, Park JH, Oh SJ, Kim HJ, Cho YK, et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci. 2006;51:1371–9.PubMedCrossRef
5.
Zurück zum Zitat Zhang XL, Yang YS, Xu DP, Qu JH, Guo MZ, Gong Y, et al. Comparative study on overexpression of HER2/neu and HER3 in gastric cancer. World J Surg. 2009;33:2112–8.PubMedCrossRef Zhang XL, Yang YS, Xu DP, Qu JH, Guo MZ, Gong Y, et al. Comparative study on overexpression of HER2/neu and HER3 in gastric cancer. World J Surg. 2009;33:2112–8.PubMedCrossRef
6.
Zurück zum Zitat Uchino S, Tsuda H, Maruyama K, Kinoshita T, Sasako M, Saito T, et al. Overexpression of c-erbB-2 protein in gastric cancer. Its correlation with long-term survival of patients. Cancer. 1993;72:3179–84.PubMedCrossRef Uchino S, Tsuda H, Maruyama K, Kinoshita T, Sasako M, Saito T, et al. Overexpression of c-erbB-2 protein in gastric cancer. Its correlation with long-term survival of patients. Cancer. 1993;72:3179–84.PubMedCrossRef
7.
Zurück zum Zitat Nakajima M, Sawada H, Yamada Y, Watanabe A, Tatsumi M, Yamashita J, et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer. 1999;85:1894–902.PubMed Nakajima M, Sawada H, Yamada Y, Watanabe A, Tatsumi M, Yamashita J, et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer. 1999;85:1894–902.PubMed
8.
Zurück zum Zitat Allgayer H, Babic R, Gruetzner KU, Tarabichi A, Schildberg FW, Heiss MM. c-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems. J Clin Oncol. 2000;18:2201–9.PubMed Allgayer H, Babic R, Gruetzner KU, Tarabichi A, Schildberg FW, Heiss MM. c-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems. J Clin Oncol. 2000;18:2201–9.PubMed
9.
Zurück zum Zitat García I, Vizoso F, Martín A, Sanz L, Abdel-Lah O, Raigoso P, et al. Clinical significance of the epidermal growth factor receptor and HER2 receptor in resectable gastric cancer. Ann Surg Oncol. 2003;10:234–41.PubMedCrossRef García I, Vizoso F, Martín A, Sanz L, Abdel-Lah O, Raigoso P, et al. Clinical significance of the epidermal growth factor receptor and HER2 receptor in resectable gastric cancer. Ann Surg Oncol. 2003;10:234–41.PubMedCrossRef
10.
Zurück zum Zitat Tanner M, Hollmén M, Junttila TT, Kapanen AI, Tommola S, Soini Y, et al. Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 2005;16:273–8.PubMedCrossRef Tanner M, Hollmén M, Junttila TT, Kapanen AI, Tommola S, Soini Y, et al. Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 2005;16:273–8.PubMedCrossRef
11.
Zurück zum Zitat Yonemura Y, Ninomiya I, Yamaguchi A, Fushida S, Kimura H, Ohoyama S, et al. Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. Cancer Res. 1991;51:1034–8.PubMed Yonemura Y, Ninomiya I, Yamaguchi A, Fushida S, Kimura H, Ohoyama S, et al. Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. Cancer Res. 1991;51:1034–8.PubMed
12.
Zurück zum Zitat Pinto-de-Sousa J, David L, Almeida R, Leitão D, Preto JR, Seixas M, et al. c-erb B-2 expression is associated with tumor location and venous invasion and influences survival of patients with gastric carcinoma. Int J Surg Pathol. 2002;10:247–56.PubMedCrossRef Pinto-de-Sousa J, David L, Almeida R, Leitão D, Preto JR, Seixas M, et al. c-erb B-2 expression is associated with tumor location and venous invasion and influences survival of patients with gastric carcinoma. Int J Surg Pathol. 2002;10:247–56.PubMedCrossRef
13.
Zurück zum Zitat Kim MA, Jung EJ, Lee HS, Lee HE, Jeon YK, Yang HK, et al. Evaluation of HER-2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction. Hum Pathol. 2007;38:1386–93.PubMedCrossRef Kim MA, Jung EJ, Lee HS, Lee HE, Jeon YK, Yang HK, et al. Evaluation of HER-2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction. Hum Pathol. 2007;38:1386–93.PubMedCrossRef
14.
Zurück zum Zitat Marx AH, Tharun L, Muth J, Dancau AM, Simon R, Yekebas E, et al. HER-2 amplification is highly homogenous in gastric cancer. Hum Pathol. 2009;40:769–77.PubMedCrossRef Marx AH, Tharun L, Muth J, Dancau AM, Simon R, Yekebas E, et al. HER-2 amplification is highly homogenous in gastric cancer. Hum Pathol. 2009;40:769–77.PubMedCrossRef
15.
Zurück zum Zitat Grabsch H, Sivakumar S, Gray S, Gabbert HE, Müller W. HER2 expression in gastric cancer: rare, heterogeneous and of no prognostic value—conclusions from 924 cases of two independent series. Cell Oncol. 2010;32:57–65.PubMed Grabsch H, Sivakumar S, Gray S, Gabbert HE, Müller W. HER2 expression in gastric cancer: rare, heterogeneous and of no prognostic value—conclusions from 924 cases of two independent series. Cell Oncol. 2010;32:57–65.PubMed
16.
Zurück zum Zitat Kunz PL, Mojtahed A, Fisher GA, Ford JM, Chang DT, Balise RR, et al. HER2 Expression in gastric and gastroesophageal junction adenocarcinoma in a US population: clinicopathologic analysis with proposed approach to HER2 assessment. Appl Immunohistochem Mol Morphol. 2011;40(36):9212–20. Kunz PL, Mojtahed A, Fisher GA, Ford JM, Chang DT, Balise RR, et al. HER2 Expression in gastric and gastroesophageal junction adenocarcinoma in a US population: clinicopathologic analysis with proposed approach to HER2 assessment. Appl Immunohistochem Mol Morphol. 2011;40(36):9212–20.
17.
Zurück zum Zitat Lee KE, Lee HJ, Kim YH, Yu HJ, Yang HK, Kim WH, et al. Prognostic significance of p53, nm23, PCNA and c-erbB-2 in gastric cancer. Jpn J Clin Oncol. 2003;33:173–9.PubMedCrossRef Lee KE, Lee HJ, Kim YH, Yu HJ, Yang HK, Kim WH, et al. Prognostic significance of p53, nm23, PCNA and c-erbB-2 in gastric cancer. Jpn J Clin Oncol. 2003;33:173–9.PubMedCrossRef
18.
Zurück zum Zitat Yu GZ, Chen Y, Wang JJ. Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance. J Cancer Res Clin Oncol. 2009;135:1331–9.PubMedCrossRef Yu GZ, Chen Y, Wang JJ. Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance. J Cancer Res Clin Oncol. 2009;135:1331–9.PubMedCrossRef
19.
Zurück zum Zitat Barros-Silva JD, Leitão D, Afonso L, Vieira J, Dinis-Ribeiro M, Fragoso M, et al. Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients. Br J Cancer. 2009;100:487–93.PubMedCrossRef Barros-Silva JD, Leitão D, Afonso L, Vieira J, Dinis-Ribeiro M, Fragoso M, et al. Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients. Br J Cancer. 2009;100:487–93.PubMedCrossRef
20.
Zurück zum Zitat Wakatsuki K, Yamada Y, Narikiyo M, Ueno M, Takayama T, Tamaki H, et al. Clinicopathological and prognostic significance of mucin phenotype in gastric cancer. J Surg Oncol. 2008;98:124–9.PubMedCrossRef Wakatsuki K, Yamada Y, Narikiyo M, Ueno M, Takayama T, Tamaki H, et al. Clinicopathological and prognostic significance of mucin phenotype in gastric cancer. J Surg Oncol. 2008;98:124–9.PubMedCrossRef
21.
Zurück zum Zitat Yokozaki H, Kuniyasu H, Kitadai Y, Nishimura K, Todo H, Ayhan A, et al. p53 point mutations in primary human gastric carcinomas. J Cancer Res Clin Oncol. 1992;119:67–70.PubMedCrossRef Yokozaki H, Kuniyasu H, Kitadai Y, Nishimura K, Todo H, Ayhan A, et al. p53 point mutations in primary human gastric carcinomas. J Cancer Res Clin Oncol. 1992;119:67–70.PubMedCrossRef
22.
Zurück zum Zitat Al-Moundhri MS, Nirmala V, Al-Hadabi I, Al-Mawaly K, Burney I, Al-Nabhani M, et al. The prognostic significance of p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67 proteins expression in gastric cancer: a clinicopathological and immunohistochemical study of 121 Arab patients. J Surg Oncol. 2005;91:243–52.PubMedCrossRef Al-Moundhri MS, Nirmala V, Al-Hadabi I, Al-Mawaly K, Burney I, Al-Nabhani M, et al. The prognostic significance of p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67 proteins expression in gastric cancer: a clinicopathological and immunohistochemical study of 121 Arab patients. J Surg Oncol. 2005;91:243–52.PubMedCrossRef
23.
Zurück zum Zitat Rüschoff J, Dietel M, Baretton G, Arbogast S, Walch A, Monges G, et al. HER2 diagnostics in gastric cancer–guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 2010;457:299–307.PubMedCrossRef Rüschoff J, Dietel M, Baretton G, Arbogast S, Walch A, Monges G, et al. HER2 diagnostics in gastric cancer–guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 2010;457:299–307.PubMedCrossRef
24.
Zurück zum Zitat Toda Y, Kono K, Abiru H, Kokuryo K, Endo M, Yaegashi H, et al. Application of tyramide signal amplification system to immunohistochemistry: a potent method to localize antigens that are not detectable by ordinary method. Pathol Int. 1999;49:479–83.PubMedCrossRef Toda Y, Kono K, Abiru H, Kokuryo K, Endo M, Yaegashi H, et al. Application of tyramide signal amplification system to immunohistochemistry: a potent method to localize antigens that are not detectable by ordinary method. Pathol Int. 1999;49:479–83.PubMedCrossRef
25.
Zurück zum Zitat Ismail HM, Moneer M, El-Baradie M, Khorshid O, Touny A. Clinicopathologic and prognostic significance of overexpression of her-2/neu and p53 oncoproteins in gastric carcinoma using tissue microarray. J Egypt Natl Cancer Inst. 2007;19:147–57. Ismail HM, Moneer M, El-Baradie M, Khorshid O, Touny A. Clinicopathologic and prognostic significance of overexpression of her-2/neu and p53 oncoproteins in gastric carcinoma using tissue microarray. J Egypt Natl Cancer Inst. 2007;19:147–57.
26.
Zurück zum Zitat Eom BW, Yoon H, Ryu KW, Lee JH, Cho SJ, Lee JY, et al. Predictors of timing and patterns of recurrence after curative resection for gastric cancer. Dig Surg. 2010;27:481–6.PubMedCrossRef Eom BW, Yoon H, Ryu KW, Lee JH, Cho SJ, Lee JY, et al. Predictors of timing and patterns of recurrence after curative resection for gastric cancer. Dig Surg. 2010;27:481–6.PubMedCrossRef
27.
Zurück zum Zitat Yan B, Yau EX, Bte Omar SS, Ong CW, Pang B, Yeoh KG, et al. A study of HER2 gene amplification and protein expression in gastric cancer. J Clin Pathol. 2010;63:839–42.PubMedCrossRef Yan B, Yau EX, Bte Omar SS, Ong CW, Pang B, Yeoh KG, et al. A study of HER2 gene amplification and protein expression in gastric cancer. J Clin Pathol. 2010;63:839–42.PubMedCrossRef
28.
Zurück zum Zitat Yan SY, Hu Y, Fan JG, Tao GQ, Lu YM, Cai X, et al. Clinicopathologic significance of HER-2/neu protein expression and gene amplification in gastric carcinoma. World J Gastroenterol. 2011;17:1501–6.PubMedCrossRef Yan SY, Hu Y, Fan JG, Tao GQ, Lu YM, Cai X, et al. Clinicopathologic significance of HER-2/neu protein expression and gene amplification in gastric carcinoma. World J Gastroenterol. 2011;17:1501–6.PubMedCrossRef
29.
Zurück zum Zitat Im SA, Kim JW, Kim JS, Kim MA, Jordan B, Pickl M, et al. Clinicopathologic characteristics of patients with stage III/IV (M(0)) advanced gastric cancer, according to HER2 status assessed by immunohistochemistry and fluorescence in situ hybridization. Diagn Mol Pathol. 2011;20:94–100.PubMedCrossRef Im SA, Kim JW, Kim JS, Kim MA, Jordan B, Pickl M, et al. Clinicopathologic characteristics of patients with stage III/IV (M(0)) advanced gastric cancer, according to HER2 status assessed by immunohistochemistry and fluorescence in situ hybridization. Diagn Mol Pathol. 2011;20:94–100.PubMedCrossRef
30.
Zurück zum Zitat Boers JE, Meeuwissen H, Methorst N. HER2 status in gastro-oesophageal adenocarcinomas assessed by two rabbit monoclonal antibodies (SP3 and 4B5) and two in situ hybridization methods (FISH and SISH). Histopathology. 2011;58:383–94.PubMedCrossRef Boers JE, Meeuwissen H, Methorst N. HER2 status in gastro-oesophageal adenocarcinomas assessed by two rabbit monoclonal antibodies (SP3 and 4B5) and two in situ hybridization methods (FISH and SISH). Histopathology. 2011;58:383–94.PubMedCrossRef
31.
Zurück zum Zitat Moelans CB, Milne AN, Morsink FH, Offerhaus GJ, van Diest PJ. Low frequency of HER2 amplification and overexpression in early onset gastric cancer. Cell Oncol (Dordr). 2011;34:89–95. Moelans CB, Milne AN, Morsink FH, Offerhaus GJ, van Diest PJ. Low frequency of HER2 amplification and overexpression in early onset gastric cancer. Cell Oncol (Dordr). 2011;34:89–95.
32.
Zurück zum Zitat Lee OJ, Kim HJ, Kim JR, Watanabe H. The prognostic significance of the mucin phenotype of gastric adenocarcinoma and its relationship with histologic classifications. Oncol Rep. 2009;21:387–93.PubMedCrossRef Lee OJ, Kim HJ, Kim JR, Watanabe H. The prognostic significance of the mucin phenotype of gastric adenocarcinoma and its relationship with histologic classifications. Oncol Rep. 2009;21:387–93.PubMedCrossRef
33.
34.
Zurück zum Zitat Oren M. Lonely no more: p53 finds its kin in a tumor suppressor haven. Cell. 1997;90:829–32.PubMedCrossRef Oren M. Lonely no more: p53 finds its kin in a tumor suppressor haven. Cell. 1997;90:829–32.PubMedCrossRef
35.
Zurück zum Zitat Yano T, Doi T, Ohtsu A, Boku N, Hashizume K, Nakanishi M, et al. Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol Rep. 2006;15:65–71. Yano T, Doi T, Ohtsu A, Boku N, Hashizume K, Nakanishi M, et al. Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol Rep. 2006;15:65–71.
36.
Zurück zum Zitat Albarello L, Pecciarini L, Doglioni C. HER2 testing in gastric cancer. Adv Anat Pathol. 2011;18:53–9.PubMedCrossRef Albarello L, Pecciarini L, Doglioni C. HER2 testing in gastric cancer. Adv Anat Pathol. 2011;18:53–9.PubMedCrossRef
Metadaten
Titel
HER2 expression and its clinicopathological features in resectable gastric cancer
verfasst von
Yoshiki Kataoka
Hiroshi Okabe
Akihiko Yoshizawa
Sachiko Minamiguchi
Kenichi Yoshimura
Hironori Haga
Yoshiharu Sakai
Publikationsdatum
01.01.2013
Verlag
Springer Japan
Erschienen in
Gastric Cancer / Ausgabe 1/2013
Print ISSN: 1436-3291
Elektronische ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-012-0150-9

Weitere Artikel der Ausgabe 1/2013

Gastric Cancer 1/2013 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

CME: 2 Punkte

Prof. Dr. med. Gregor Antoniadis Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

CME: 2 Punkte

Dr. med. Benjamin Meyknecht, PD Dr. med. Oliver Pieske Das Webinar S2e-Leitlinie „Distale Radiusfraktur“ beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

CME: 2 Punkte

Dr. med. Mihailo Andric
Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.