Aktuelle Urol 2016; 47(06): 475-479
DOI: 10.1055/s-0042-115401
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

c-Met Onkogen bei Nierenzellkarzinomen

c-MET Oncogene in Renal Cell Carcinomas
F. Erlmeier
1   Institut für Pathologie, Technische Universität München
2   Mitglied des Deutschen Netzwerks Nierenzelltumoren
,
W. Weichert
1   Institut für Pathologie, Technische Universität München
3   Mitglied des Deutschen Konsortiums für Translationale Krebsforschung (DKTK)
,
M. Autenrieth
4   Klinik und Poliklinik für Urologie, Klinikum rechts der Isar, Technische Universität München
,
P. Ivanyi
5   Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover
,
A. Hartmann
2   Mitglied des Deutschen Netzwerks Nierenzelltumoren
6   Institut für Pathologie, Universität Erlangen
,
S. Steffens
2   Mitglied des Deutschen Netzwerks Nierenzelltumoren
7   Klinik für Urologie und Kinderurologie, Universitätsklinikum Münster
› Author Affiliations
Further Information

Publication History

Publication Date:
22 December 2016 (online)

Zusammenfassung

c-Met spielt eine bedeutende Rolle in einer Vielzahl zellulärer Prozesse. Als Protoonkogen unterstützt die Tyrosinkinase aggressives Tumorverhalten, wie z. B. invasives Tumorwachstum und Metastasenbildung. Für einige Subtypen des Nierenzellkarzinoms (NZK) zeigt sich ein mehrfach belegter Zusammenhang zwischen der Höhe der c-Met Expression und dem Krankheitsverlauf bzw. der Prognose. c-Met stellt somit beim NZK einen prognostischen Marker dar.

Darüber hinaus wird c-Met in der Ära der personalisierten Medizin als möglicher Angriffspunkt gezielter Therapien eine bedeutende Rolle spielen. Vor allem beim klarzelligen NZK erlangt die duale VEGF und c-Met Tyrosinkinase-Hemmung bei metastasierten, therapierefraktären Tumoren zunehmend klinische Relevanz. Die Bedeutung von c-Met ist bis dato noch nicht gänzlich für alle Subtypen des NZK geklärt. Die Relevanz von c-Met bei den übrigen NZK gilt es noch abschließend zu klären.

Summary

c-Met plays a significant role in multiple cellular processes. Being encoded by a proto-oncogene, tyrosine kinase supports aggressive tumour behaviour such as tumour invasiveness and formation of metastases. For some subtypes of renal cell carcinoma studies have shown a association between c-Met expression and clinical outcome or prognosis. Therefore, c-Met represents a prognostic marker in renal cell carcinoma.

Furthermore, c-MET will play a decisive role as a possible target for targeted therapies in the era of personalised medicine. Especially for RCC, the dual inhibition of VEGF and c-MET tyrosine kinase in cases of metastatic, treatment-resistant tumours is gaining clinical relevance. The role of c-Met has not been fully elucidated for all subtypes of renal cell carcinomas. The relevance of c-Met for the remaining subtypes of renal tumours has yet to be clarified.

 
  • Literatur

  • 1 Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med. 2005; 353: 2477-2490
  • 2 Escudier B, Porta C, Schmidinger M et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014; 25 (Suppl. 03) iii49-iii56
  • 3 Motzer RJ, Hutson TE, McCann L et al. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med. 2014; 370: 1769-1770
  • 4 Coppin C, Porzsolt F, Awa A et al. Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev. 2005 CD001425
  • 5 Ivanyi P, Grunwald V. Systemic Treatment of Metastatic Renal Cell Cancer – Back to the Future?. Aktuelle Urol 2015; 46: 467-472
  • 6 Brugarolas J. Renal-cell carcinoma – molecular pathways and therapies. N Engl J Med. 2007; 356: 185-187
  • 7 Graziani A, Gramaglia D, Cantley LC et al. The tyrosine-phosphorylated hepatocyte growth factor/scatter factor receptor associates with phosphatidylinositol 3-kinase. J Biol Chem. 1991; 266: 22087-22090
  • 8 Monga SP, Mars WM, Pediaditakis P et al. Hepatocyte growth factor induces Wnt-independent nuclear translocation of beta-catenin after Met-beta-catenin dissociation in hepatocytes. Cancer Res. 2002; 62: 2064-2071
  • 9 Gentile A, Trusolino L, Comoglio PM. The Met tyrosine kinase receptor in development and cancer. Cancer Metastasis Rev. 2008; 27: 85-94
  • 10 Han Y, Luo Y, Zhao J et al. Overexpression of c-Met increases the tumor invasion of human prostate LNCaP cancer cells in vitro and in vivo. Oncol Lett 2014; 8: 1618-1624
  • 11 Ogunwobi OO, Puszyk W, Dong HJ et al. Epigenetic upregulation of HGF and c-Met drives metastasis in hepatocellular carcinoma. PLoS One 2013; 8: e63765
  • 12 Smyth EC, Sclafani F, Cunningham D. Emerging molecular targets in oncology: clinical potential of MET/hepatocyte growth-factor inhibitors. Onco Targets Ther 2014; 7: 1001-1014
  • 13 Previdi S, Maroni P, Matteucci E et al. Interaction between human-breast cancer metastasis and bone microenvironment through activated hepatocyte growth factor/Met and beta-catenin/Wnt pathways. Eur J Cancer. 2010; 46: 1679-1691
  • 14 Muckenhuber A, Babitzki G, Thomas M et al. Profiling of cMET and HER Family Receptor Expression in Pancreatic Ductal Adenocarcinomas and Corresponding Lymph Node Metastasis to Assess Relevant Pathways for Targeted Therapies: Looking at the Soil Before Planting the Seed. Pancreas 2016; DOI: 10.1097/MPA.0000000000000604.
  • 15 Baccelli I, Stenzinger A, Vogel V et al. Co-expression of MET and CD47 is a novel prognosticator for survival of luminal breast cancer patients. Oncotarget 2014; 5: 8147-8160
  • 16 Kovacs G, Akhtar M, Beckwith BJ et al. The Heidelberg classification of renal cell tumours. J Pathol. 1997; 183: 131-133
  • 17 Sircar K, Rao P, Jonasch E et al. Contemporary approach to diagnosis and classification of renal cell carcinoma with mixed histologic features. Chin J Cancer 2013; 32: 303-311
  • 18 Razafinjatovo C, Bihr S, Mischo A et al. Characterization of VHL missense mutations in sporadic clear cell renal cell carcinoma: hotspots, affected binding domains, functional impact on pVHL and therapeutic relevance. BMC Cancer 2016; 16: 638
  • 19 Oh RR, Park JY, Lee JH et al. Expression of HGF/SF and Met protein is associated with genetic alterations of VHL gene in primary renal cell carcinomas. Apmis 2002; 110: 229-238
  • 20 Gibney GT, Aziz SA, Camp RL et al. c-Met is a prognostic marker and potential therapeutic target in clear cell renal cell carcinoma. Ann Oncol. 2013; 24: 343-349
  • 21 Miyata Y, Kanetake H, Kanda S. Presence of phosphorylated hepatocyte growth factor receptor/c-Met is associated with tumor progression and survival in patients with conventional renal cell carcinoma. Clin Cancer Res. 2006; 12: 4876-4881
  • 22 Betsunoh H, Mukai S, Akiyama Y et al. Clinical relevance of hepsin and hepatocyte growth factor activator inhibitor type 2 expression in renal cell carcinoma. Cancer Sci. 2007; 98: 491-498
  • 23 Torti D, Trusolino L. Oncogene addiction as a foundational rationale for targeted anti-cancer therapy: promises and perils. EMBO Mol Med 2011; 3: 623-636
  • 24 Sherman SI, Clary DO, Elisei R et al. Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer. Cancer 2016; DOI: 10.1002/cncr.30252.
  • 25 Choueiri TK, Escudier B, Powles T et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016; DOI: 10.1016/S1470-2045(16)30107-3.
  • 26 Choueiri TK, Powles T, Escudier B et al. Overall survival (OS) in METEOR, a randomized phase 3 trial of cabozantinib (Cabo) versus everolimus (Eve) in patients (pts) with advanced renal cell carcinoma (RCC). J Clin Oncol 2016; 34 (Suppl): abstr 4506
  • 27 Steffens S, Roos FC, Janssen M et al. Clinical behavior of chromophobe renal cell carcinoma is less aggressive than that of clear cell renal cell carcinoma, independent of Fuhrman grade or tumor size. Virchows Arch. 2014; 465: 439-444
  • 28 Roos FC, Steffens S, Junker K et al. Survival advantage of partial over radical nephrectomy in patients presenting with localized renal cell carcinoma. BMC Cancer 2014; 14: 372
  • 29 Steffens S, Kohler A, Rudolph R et al. Validation of CRP as prognostic marker for renal cell carcinoma in a large series of patients. BMC Cancer 2012; 12: 399
  • 30 Escudier B, Porta C, Schmidinger M et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014; 25 (Suppl. 03) iii49-iii56
  • 31 Schrader AJ, Steffens S. Renal Cell Carcinoma Update: News from the AUA, EAU, and ASCO Annual Meetings 2011. ISRN Urol 2012; 2012: 748235
  • 32 Lindor NM, Dechet CB, Greene MH et al. Papillary renal cell carcinoma: analysis of germline mutations in the MET proto-oncogene in a clinic-based population. Genet Test. 2001; 5: 101-106
  • 33 Bigot P, Bernhard JC, Gill IS et al. The subclassification of papillary renal cell carcinoma does not affect oncological outcomes after nephron sparing surgery. World J Urol. 2016; 34: 347-352
  • 34 Schmidt L, Junker K, Nakaigawa N et al. Novel mutations of the MET proto-oncogene in papillary renal carcinomas. Oncogene 1999; 18: 2343-2350
  • 35 Lager DJ, Huston BJ, Timmerman TG et al. Papillary renal tumors. Morphologic, cytochemical, and genotypic features. Cancer 1995; 76: 669-673
  • 36 Cancer Genome Atlas Research Network . Linehan WM, Spellman PT et al. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma. N Engl J Med. 2016; 374: 135-145
  • 37 Sweeney P, El-Naggar AK, Lin SH et al. Biological significance of c-met over expression in papillary renal cell carcinoma. J Urol. 2002; 168: 51-55
  • 38 Choueiri TK, Vaishampayan U, Rosenberg JE et al. Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma. J Clin Oncol. 2013; 31: 181-186
  • 39 Thoenes W, Storkel S, Rumpelt HJ. Human chromophobe cell renal carcinoma. Virchows Arch B Cell Pathol Incl Mol Pathol. 1985; 48: 207-217
  • 40 Moch H, Gasser T, Amin MB et al. Prognostic utility of the recently recommended histologic classification and revised TNM staging system of renal cell carcinoma: a Swiss experience with 588 tumors. Cancer 2000; 89: 604-614
  • 41 Cindolo L, Patard JJ, Chiodini P et al. Comparison of predictive accuracy of four prognostic models for nonmetastatic renal cell carcinoma after nephrectomy: a multicenter European study. Cancer 2005; 104: 1362-1371
  • 42 Crotty TB, Farrow GM, Lieber MM. Chromophobe cell renal carcinoma: clinicopathological features of 50 cases. J Urol. 1995; 154: 964-967
  • 43 Renshaw AA, Henske EP, Loughlin KR et al. Aggressive variants of chromophobe renal cell carcinoma. Cancer 1996; 78: 1756-1761
  • 44 Renshaw AA, Richie JP. Subtypes of renal cell carcinoma. Different onset and sites of metastatic disease. Am J Clin Pathol 1999; 111: 539-543
  • 45 Ohe C, Kuroda N, Takasu K et al. Utility of immunohistochemical analysis of KAI1, epithelial-specific antigen, and epithelial-related antigen for distinction of chromophobe renal cell carcinoma, an eosinophilic variant from renal oncocytoma. Med Mol Morphol. 2012; 45: 98-104
  • 46 Wang CC, Mao TL, Yang WC et al. Underexpression of hepatocyte nuclear factor-1beta in chromophobe renal cell carcinoma. Histopathology 2013; 62: 589-594
  • 47 Schoffski P, Garcia JA, Stadler WM et al. A phase II study of the efficacy and safety of AMG 102 in patients with metastatic renal cell carcinoma. BJU Int 2011; 108: 679-686