Immunohistochemical study of Epidermal Growth Factor Receptor (EGFR), Hepatocyte Growth Factor (HGF), c-MET, Vascular Endothelial Growth Factor (VEGF) and CD34 in non small cell carcinomas of the lung Abbreviated title: Immunohistochemical study of NSCLC

Immunohistochemical study of Epidermal Growth Factor Receptor (EGFR), Hepatocyte Growth Factor (HGF), c-MET, Vascular Endothelial Growth Factor (VEGF) and CD34 in non small cell carcinomas of the lung Abbreviated title: Immunohistochemical study of NSCLC

Maria Sakalidou, Dimitrios Bouklas, Georgia-Heleni Thomopoulou, Sophia Tseleni, Andreas C. Lazaris, Nikolaos Kavantzas

Abstract


Abstract

Aim: The aim of our study was the immunohistochemical investigation of the expression of Epidermal Growth Factor Receptor (EGFR), Hepatocyte Growth Factor (HGF), c-MET and Vascular Endothelial Growth Factor (VEGF) in non small cell lung cancer (NSCLC) tissue samples.

Materials and Methods: Forty seven cases of NSCLC were selected from the archive material of the First Department of Pathology of National and Kapodistrian University of Athens. The immunohistochemical staining was performed using anti- EGFR/ HGF/c-MET/VEGF/ CD 34 antibodies. The immunoexpression was correlated with angiogenesis events, using the CD34 marker, and a qualitative and quantitative evaluation was performed. All data were statistically correlated with each other, so as with various clinicopathologic parameters τοο, in an attempt to draw conclusions about their prognostic significance.

Results: VEGF expression was found to be higher in squamous cell carcinomas and was negatively associated with the expression of CD34 and HGF. The last two were positively correlated with higher tumor grades and disease stage. CD34 and HGF expression was found to be higher in adenocarcinomas. Lastly, CD34 and HGF expression was found to be associated with lymph node infiltration.

Conclusions:

The expression of the selected markers varies among different histological types of NSCLC.

Tumors with a positive expression of CD34 are more aggressive (high grade).

Tumors with positive expression of angiogenic factors are diagnosed at an advanced stage of the disease.

 


Keywords


Epidermal Growth Factor Receptor, Hepatocyte Growth Factor/c-MET, Vascular Endothelial Growth Factor, CD34, non small cell lung cancer

Full Text:

READ AS PDF

References


Charles S. Dela Cruz, Lynn T. Tanoue, Richard A. Matthay, Lung Cancer. Epidemiology, Etiology and Prevention. Clin Chest Med 2011; 32 (4):605-644

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864624/

Travis W.D. ed ,Brambilla E. ed, Burke A.P. ed , Marx A. ed ,Nicholson A.G ed, WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart, 4th edition, WHO Press; 2015

Gullick W J. Prevalence of aberrant expression of the epidermal growth factor receptor in human cancers. Br Med Bull 1991; 47:87-98

http://www.ncbi.nlm.nih.gov/pubmed/1863851

Lin SY, Makino K, Xia W, Matin A, Wen Y, Kwong KY et al. Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol 2001; 3(9):802-808

http://www.ncbi.nlm.nih.gov/pubmed/11533659

Naldini L, Vigna E, Narsimhan RP, Gaudini G, Zarnegar R, Michalopoulos GK et al. Hepatocyte growth factor stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET. Oncogene 1991; 6:501-504

I.Watermann, B. Schmitt , Stellmacher, J. Müller, R. Gaber, Ch. Kugler et al. Improved diagnostics targeting c-MET in non-small cell lung cancer: expression, amplification and activation. Diagn Pathol 2015; 10:130

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517562/

Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev 1997; 18:4-25

Vermeulen P. B., Gasparini G., Fox P. B., Toi M., Martin L., McCulloch P. et al. Quantification of angiogenesis in solid human tumors: an international consensus on the methodology and criteria of evaluation. Eur. J. Cancer 1996; 32A:2474-2484

Jun Ya Nakade, Shinji Takeuchi, Takayuki Nakazawa, Daisuke Ichikawa, Takako Sano, Shigeki Nanjo et al. Triple Inhibition of EGFR, Met, and VEGF Suppresses Regrowth of HGF-Triggered, Erlotinib-Resistant Lung Cancer Harboring an EGFR Mutation. J Thorac Oncol 2014; 9(6):775-783

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132034/

Fumihiro Tanaka, Yosuke Otake, Kazuhiro Yanagihara, Yozo Kawano, Ryo Miyahara, Mio Li et al. Evaluation of Angiogenesis in Non-small Cell Lung Cancer: Comparison between Anti-CD34 Antibody and Anti-CD105. Antibody Clin Cancer Res 2001; 7:3410 http://clincancerres.aacrjournals.org/content/clincanres/7/11/3410.full.pdf

T C Mineo, V Ambrogi, A Baldi, C Rabitti, P Bolero, B Vincenzi et al. Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumour vessel invasion after radical surgery for IB–IIA non-small cell lung cancer. Clin Pathol 2004; 57:591–597

http://www.ncbi.nlm.nih.gov/pubmed/15166262

Manhua Ding, Liang Liu, Chengxi Hu, Yi Liu, Yun Qiao, Xiaodong Jiang. Expression of VEGFR2 and NRP-1 in non-small cell lung cancer and their clinical significance. Chin J Cancer Res 2014; 26(6):669–677http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279211/

Bing Z, Jian-ru Y, Yao-quan J, Shi-feng C. Evaluation of angiogenesis in non-small cell lung carcinoma by CD34 immunohistochemistry. Cell Biochem Biophys 2014;70(1):327-331

http://www.ncbi.nlm.nih.gov/pubmed/24676677

Greenblatt MS, Bennett V/P, Hollstein M. Mutations in the p53

tumor suppressor gene: Clues to cancer etiology and molecular pathogenesis. Cancer Res 1994; 54:4855-4878

Tsao MS, Aviel-Ronen S, Ding K, Lau K, Li Ν.Prognostic and

predictive importance of p53 and ras for adjuvant chemotherapy in

NSCLC. J Clin Oncol 2007; 25:5240-5247

http://www.ncbi.nlm.nih.gov/pubmed/18024870

Yano T, Tanikawa S, Fujie T. Vascular endothelial growth factor expression and neovascularization in non-small cell lung cancer. Eur J Cancer 2000; 36:601–609

A.M.Inda L.B. Andrini, M.N. Garcia, A.L. Garcia, A. Fernandez Blanco, C.C. Furnace et al. Evaluation of Angiogenesis with the Expression of VEGF and CD34 in Human Non-Small Cell Lung Cancer. J. Exp.Clin. Cancer Res. 2007; 26:3

http://www.ncbi.nlm.nih.gov/pubmed/17987799

Ghio P., Cappia S., Selvaggi G. Prognostic role of protease-activated receptors 1 and 4 in resected stage IB non small-cells lung cancer. Clin. Lung Cancer 2006; 7:395-400

http://europepmc.org/abstract/med/16800965

Nakashima T., Huang C.L., Liu D. Expression of vascular endothelial growth factor - A and vascular endothelial growth factor - C as prognostic factors for non-small cell lung cancer. Med. Sci. Monit 2004; 10:157-165

http://www.ncbi.nlm.nih.gov/pubmed/15173661

Zhang N, Xie F, Gao W, Yu S, Qiu L, Lin W et al. Expression of hepatocyte growth factor and c-Met in non-small-cell lung cancer and association with lymphangiogenesis. Mol Med Rep 2015;11(4):2797-2804 http://www.ncbi.nlm.nih.gov/pubmed/25504327


Refbacks

  • There are currently no refbacks.



Copyright 2015-2017, Hellenic Society of Pathology
ISSN: 2459-3443